tag:blogger.com,1999:blog-18198226430503078432024-03-27T11:09:20.160+01:00REMOTEcat projectWelcome to the blog of the project entitled "Asymmetric organocatalysts for remote functionalization strategies" (REMOTEcat).
The aim of this blog is to disseminate the basic principles of asymmetric catalysis and its relevance in chemistry to non-specialists.
This blog reflects only the author's view. EU is not liable for any use that may be made of the information contained herein.Fernandohttp://www.blogger.com/profile/12522654073566755853noreply@blogger.comBlogger20125tag:blogger.com,1999:blog-1819822643050307843.post-68416013547430923442017-12-03T21:07:00.000+01:002017-12-04T22:24:59.789+01:00The three pillars of asymmetric catalysis<div style="text-align: justify;">
Breakthrough research of Knowles, Noyori and Sharpless positioned asymmetric catalysis as one of the most prominent methods for the synthesis of chiral compounds. The catalysts they used rely on (transition) metals. Metals offer a wide range of activity and selectivity in a vast range of chemical reactions. Despite of the fact that for decades, the generally accepted view has been that metals dominate the area there are also two classes of efficient asymmetric catalysts: enzymes (biocatalysis) and small organic molecules (organocatalysis). Together with metal catalysis constitute what is nowadays coined as the three pillars of asymmetric catalysis.</div>
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Let us mimic the Mother Nature!</b><br />
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Over millions of years of continuous evolution, Nature has perfected its machinery to a superb level. Many chemical reactions occur in living organisms in such precision that chemists have pursued the challenge of imitating Nature to carry out chemical reactions. Most biological molecules are chiral and are synthesized in living cells by enzymes using asymmetric catalysis. Chemists also use enzymes or even whole cells to synthesize chiral compounds and for a long time, the perfect enantioselectivities often observed in enzymatic reactions were considered beyond reach for non-biological catalysts.</div>
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<b>Metal catalysis</b><br />
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It became evident that high levels of enantioselectivity can also be achieved using <u>synthetic metal complexes</u> as catalysts. Therefore, organic chemists took the main components of enzymes (metal and chiral organic molecules) to design ”simplified” enzymes. Since the discovery of the potential of metal-catalysed reactions, a variety of highly efficient catalytic asymmetric reactions have been developed so far and research in asymmetric catalysis achieved prominence in both academia and industry. Despite of the great potential of metal catalysis the technology is not as greener as should be, contributing to pollution and high-cost processes, thus not offering encouraging prospects for chemical sustainability.</div>
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<b>Biocatalysis</b><br />
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Biocatalysis can be defined as the use of <u>enzymes</u> to catalyze chemical reactions. An enzyme is simply a protein catalyst, and enzymes have many important uses. Every reaction in living organisms (e.g. yourself!), proceeds thanks to the presence of enzymes. Biocatalysis can be used to replace many traditional chemical catalysts, including catalysts that are toxic or contain chemical residues that pollute the environment. The increasing ability to use enzymes to catalyse chemical reactions in industrial processes, including the production of drug substances, flavours, fragrances, or polymers — chemicals that literally impact almost every facet of your life. In adopting biocatalysis as a mainstream technology for chemical production, it is expected that greener, pollution and cost-efficient processes will be generated.</div>
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<b>Organocatalysis</b><br />
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In organocatalysis, a purely organic and <u>metal-free small molecule</u> is used to catalyse a chemical reaction. In addition to enriching chemistry with another useful strategy for catalysis, this approach has some important advantages. Small organic molecule catalysts are generally stable and easy to design and synthesize. They are often based on non-toxic compounds, such as sugars, peptides, or even amino acids, and can easily be linked to a solid support, making them useful for industrial applications. However, the property of organocatalysts most attractive to organic chemists may be the simple fact that they are organic molecules.<br />
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Metal, bio- and organocatalysis are complementary areas in asymmetric catalysis with pros and cons. Whatever option is finally selected for the synthesis of chiral compounds depends on different factors (e.g. desired activity and selectivity in the reaction of choice, cost, and waste generation). It has to be evaluated thoroughly to provide with what is more important: a sustainable and greener chemistry process.Fernandohttp://www.blogger.com/profile/12522654073566755853noreply@blogger.com1tag:blogger.com,1999:blog-1819822643050307843.post-53386915698990734712017-01-10T12:00:00.000+01:002018-05-06T16:27:38.795+02:00Publication in Angewandte Chemie International Edition (this post is for specialists only)Recently, it has been published in Angewandte Chemie International Edition research I have been involved with my lab mates Marta, and Niels.<br />
For those who are familiar with organic chemistry, you will find the link to the original article below. Hope you enjoy reading it!<br />
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<img src="https://wol-prod-cdn.literatumonline.com/cms/attachment/0f8cfd9c-4181-4301-9237-3326647162c5/anie201611306-toc-0001-m.jpg" /><br />
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<a href="http://onlinelibrary.wiley.com/doi/10.1002/anie.201611306/full" target="_blank">Synergistic Diastereo- and Enantioselective Functionalization of Unactivated Alkyl Quinolines with α,β-Unsaturated Aldehydes</a><br />
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Dr. Marta Meazza, Dr. Fernando Tur, Niels Hammer and Prof. Dr. Karl Anker Jørgensen<br />
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DOI: 10.1002/anie.201611306<br />
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Find below the abstract:<br />
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<b>A fruitful partnership</b>: InCl3 activation of unactivated alkyl quinolines has been combined with organocatalytic activation of α,β-unsaturated aldehydes. The reaction involves two consecutive synergistic catalytic cycles and provides selectively double- or mono-addition products in good yields and high to excellent stereoselectivities. Based on spectroscopic and labeling experiments, the reaction mechanisms are discussed.</div>
Fernandohttp://www.blogger.com/profile/12522654073566755853noreply@blogger.com0tag:blogger.com,1999:blog-1819822643050307843.post-9273010722786908642016-11-26T14:00:00.000+01:002016-11-26T14:00:15.665+01:00Publication in Chemical Society Reviews (this post is for specialists only)Recently, it has been published in Chemical Society Reviews a review I have been involved with my lab mates Lydia and Pernille.<br />
For those who are familiar with organic chemistry, you will find the link to the original article below. Hope you enjoy reading it!<br />
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Find below the abstract:<br />
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<b>Organocatalysis as a paint palette for asymmetric cycloaddition reactions.</b><br />
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Cycloaddition reactions are among the most important tools for the construction of cyclic compounds in organic synthesis, since these reactions are vital to access natural products and biologically active compounds. Organocatalysis plays an increasingly pivotal role in these reactions, often allowing several stereocenters to be selectively created and integrated in the target molecule. Among the large number of efficient types of organocatalysts available, the diarylprolinol silyl ethers have been established as one of the most frequently used in aminocatalysis allowing for novel activation modes and reaction concepts. In this review, we will focus on the different activation modes made available by the diarylprolinol silyl ether system with the aim of highlighting their applicability in asymmetric cycloadditions for the assembly of complex molecular architectures.</div>
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<img alt="Graphical abstract: Asymmetric cycloaddition reactions catalysed by diarylprolinol silyl ethers" height="216" id="imgGALoader" src="https://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=C6CS00713A" style="border: 0px;" title="Graphical abstract" width="320" /></div>
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<a href="http://pubs.rsc.org/en/content/articlelanding/2017/cs/c6cs00713a">Asymmetric cycloaddition reactions catalysed by diarylprolinol silyl ethers</a><br />Lydia Klier, Fernando Tur, Pernille H. Poulsen and Karl Anker Jørgensen<br />Chem. Soc. Rev., 2017, Advance Article <br />DOI: 10.1039/C6CS00713A, Review Article<br /><br /><div style="background-color: white; color: #222222; font-family: arial; font-size: 12px;">
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Fernandohttp://www.blogger.com/profile/12522654073566755853noreply@blogger.com0tag:blogger.com,1999:blog-1819822643050307843.post-29896538833362418202016-11-26T13:00:00.000+01:002018-05-31T23:05:37.589+02:00Publication in Chemistry: A European Journal (this post is for specialists only)Recently, it has been published in Chemistry: A European Journal research I have been involved with my lab mates Line, Marta, Jakob and Kim.<br />
For those who are familiar with organic chemistry, you will find the link to the original article below. Hope you enjoy reading it!<br />
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<img src="https://wol-prod-cdn.literatumonline.com/cms/attachment/a221778f-6429-408c-bbd5-8ef1cf23f20b/chem201604995-toc-0001-m.jpg" /><br />
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<a href="http://onlinelibrary.wiley.com/doi/10.1002/chem.201604995/full">Synergistic Catalysis for the Asymmetric [3+2] Cycloaddition of Vinyl Aziridines with α,β-Unsaturated Aldehydes</a><br />
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Line Næsborg, Dr. Fernando Tur, Dr. Marta Meazza, Jakob Blom, Dr. Kim Søholm Halskov and Prof. Dr. Karl Anker Jørgensen<br />
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DOI: 10.1002/chem.201604995<br />
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Find below the abstract:<br />
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The first asymmetric [3+2] cycloaddition of vinyl aziridines with α,β-unsaturated aldehydes, based on synergistic catalysis, is disclosed. This methodology allows the formation of attractive pyrrolidine structures in good yields (up to 84 %), moderate diastereoselectivity, and high enantioselectivity values (up to >99 % ee). Additionally, a tricyclic pyrrolidine core structure found in biologically active molecules was synthesized in a one-pot fashion by using the presented reaction concept. Finally, a mechanistic proposal is outlined.</div>
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<br />Fernandohttp://www.blogger.com/profile/12522654073566755853noreply@blogger.com2tag:blogger.com,1999:blog-1819822643050307843.post-28386945759964900172016-09-20T22:00:00.000+02:002017-12-04T22:25:29.460+01:00Synthesis of Tetrakis(triphenylphosphine)palladium(0) (this post is only for specialists)<div>
Here you will find a link to a video prepared by my lab mate Niels Hammer (Ph.D student, AU).</div>
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It describes the synthesis of Tetrakis(triphenylphosphine)palladium(0). It is the chemical compound of formula Pd[P(C6H5)3]4, often abbreviated Pd(PPh3)4. It is a bright yellow crystalline solid that becomes brown upon decomposition in air. Pd(PPh3)4 is widely used as a catalyst for palladium-catalyzed coupling reactions.</div>
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<iframe allowfullscreen="" class="YOUTUBE-iframe-video" data-thumbnail-src="https://i.ytimg.com/vi/d_6dFSqSXVw/0.jpg" frameborder="0" height="266" src="https://www.youtube.com/embed/d_6dFSqSXVw?feature=player_embedded" width="320"></iframe></div>
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Reference: Coulson, D. R. <i>Inorg. Synth.</i> <b>1972</b>, <i>13</i>, 121.<br />
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<b>IMPORTANT NOTE:</b></div>
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<b>This post contain information about how to prepare a chemical compound. The procedure described in this video is intended for use only by persons with prior training in experimental organic chemistry. All hazardous materials should be handled using the standard procedures for work with chemicals. All chemical waste should be disposed of in accordance with local regulations.</b><br />
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<b><b>This procedure must be conducted at one's own risk. Hereby, the owner of this blog disclaim any liability for any injuries or damages claimed to have resulted from or related in any way to the procedure described herein.</b></b></div>
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</b>Fernandohttp://www.blogger.com/profile/12522654073566755853noreply@blogger.com1tag:blogger.com,1999:blog-1819822643050307843.post-80630288506749668202016-05-08T12:00:00.000+02:002017-01-10T11:13:47.402+01:00Publication in Organic Letters (this post is for specialists only)Recently, it has been published in Organic Letters research I have been involved with my lab mates Kim, and Line.<br />
For those who are familiar with organic chemistry, you will find the link to the original article below. Hope you enjoy reading it!<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgtzD6ndMw1KsofjJ60YnLHxhJEShvzIDBZF94Yw32_unSMABxR3ZTITIhyphenhyphenmnF8icoPGfgUfmSK8Kw067sVV5Wqkb8m8Haz0BOk_DKG84Xtw82Ti6lBIB36fmNcdNZ4P27rV9ZOGUMaAVQ/s1600/ol-2016-008524_0009.gif" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="132" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgtzD6ndMw1KsofjJ60YnLHxhJEShvzIDBZF94Yw32_unSMABxR3ZTITIhyphenhyphenmnF8icoPGfgUfmSK8Kw067sVV5Wqkb8m8Haz0BOk_DKG84Xtw82Ti6lBIB36fmNcdNZ4P27rV9ZOGUMaAVQ/s400/ol-2016-008524_0009.gif" width="400" /></a></div>
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Asymmetric [3 + 2] Cycloaddition of Vinylcyclopropanes and α,β-Unsaturated Aldehydes by Synergistic Palladium and Organocatalysis</h4>
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Kim Søholm Halskov, Line Næsborg, Fernando Tur, and Karl Anker Jørgensen</div>
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<cite>Organic Letters</cite> <strong>2016</strong> <em>18</em> (9), 2220-2223</div>
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<span style="background-color: white; font-family: "arial" , "helvetica" , sans-serif; font-size: 13px; text-align: left;">DOI: 10.1021/acs.orglett.6b00852</span></div>
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<a href="http://pubs.acs.org/doi/abs/10.1021/acs.orglett.6b00852" target="_blank">http://pubs.acs.org/doi/abs/10.1021/acs.orglett.6b00852</a></div>
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<br />Fernandohttp://www.blogger.com/profile/12522654073566755853noreply@blogger.com0tag:blogger.com,1999:blog-1819822643050307843.post-5459031462457361662015-12-12T10:00:00.000+01:002017-12-03T21:11:22.546+01:00How to dry molecular sieves?<div style="text-align: justify;">
In this post, I will move from the topic of asymmetric catalysis and I will explain a basic operation in organic chemistry lab.</div>
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Laboratories involved with organic synthesis require efficient methods with which to dry (i.e. removal of water) organic solvents. In some cases, water present in organic solvents can be deleterious for the chemical reaction since reactants and/or reagents can react faster with water being deactivated with the consequent loss of performance of the reaction.</div>
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Among the different methods available for drying solvents, the use of molecular sieves is one of the most efficient ones. A molecular sieve is a material with pores (very small holes) of uniform size. These pore diameters are of the dimensions of small molecules, thus large molecules cannot be absorbed, while smaller molecules can.</div>
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<tr><td class="tr-caption" style="text-align: center;">Molecular sieves</td></tr>
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From the chemistry point of view, molecular sieves are crystalline metal aluminosilicates having a three dimensional interconnecting network of silica and alumina tetrahedra. Natural water of hydration is removed from this network by heating to produce uniform cavities which selectively adsorb molecules of a specific size.</div>
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Commercially available molecular sieves contain water, therefore it is needed to remove this water content before use as dessicant in organic solvents. This process is called "activation" of molecular sieves.</div>
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In the following video created by my lab mate Rasmus Mose (Ph.D. student, AU) you will find a short description on how to activate molecular sieves and store solvents in a schlenk flask.</div>
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Very useful in case you work in an organic chemistry lab!<br />
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<iframe allowfullscreen="" class="YOUTUBE-iframe-video" data-thumbnail-src="https://i.ytimg.com/vi/T9hPvmjftAg/0.jpg" frameborder="0" height="266" src="https://www.youtube.com/embed/T9hPvmjftAg?feature=player_embedded" width="320"></iframe></div>
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<b>IMPORTANT NOTE:</b></div>
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<b>This post contain information about an experimental procedure in a chemistry laboratory. The procedure described in this video is intended for use only by persons with prior training in experimental organic chemistry. All hazardous materials should be handled using the standard procedures for work with chemicals. All chemical waste should be disposed of in accordance with local regulations.</b></div>
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<b>This procedure must be conducted at one's own risk. Hereby, the owner of this blog disclaim any liability for any injuries or damages claimed to have resulted from or related in any way to the procedure described herein.</b></div>
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Fernandohttp://www.blogger.com/profile/12522654073566755853noreply@blogger.com2tag:blogger.com,1999:blog-1819822643050307843.post-5599493303796895882015-12-05T20:00:00.000+01:002016-01-16T18:53:32.532+01:00Publication in Angewandte Chemie International Edition (this post is for specialists only)Recently, it has been published in Angewandte Chemie International Edition research I have been involved with my lab mates Yang, Rune, and Hao.<br />
For those who are familiar with organic chemistry, you will find the link to the original article below. Hope you enjoy reading it!<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEghzssVdH71OgrDXSP5FNv2F2GnbnRag15mjHjVAa9BHRUHmNLp6GY8YBA42RM5tDN-ArLzwGjNRH4CVWOhIHXMSWOrDPbe5Qg70PXQEc1BvRTHYWmOR3_SjDAXh___yg9-_CZ3rp9JznU/s1600/graphical_abstract_acie.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="110" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEghzssVdH71OgrDXSP5FNv2F2GnbnRag15mjHjVAa9BHRUHmNLp6GY8YBA42RM5tDN-ArLzwGjNRH4CVWOhIHXMSWOrDPbe5Qg70PXQEc1BvRTHYWmOR3_SjDAXh___yg9-_CZ3rp9JznU/s400/graphical_abstract_acie.jpg" width="400" /></a></div>
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Li, Y., Tur, F., Nielsen, R. P., Jiang, H., Jensen, F. and Jørgensen, K. A. (2015), Enantioselective Formal [4+2] Cycloadditions to 3-Nitroindoles by Trienamine Catalysis: Synthesis of Chiral Dihydrocarbazoles. Angew. Chem. Int. Ed. 2015, 54, 1020-1024 doi:10.1002/anie.201509693<br />
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<a href="http://onlinelibrary.wiley.com/doi/10.1002/anie.201509693/abstract">http://onlinelibrary.wiley.com/doi/10.1002/anie.201509693/abstract</a><br />
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Fernandohttp://www.blogger.com/profile/12522654073566755853noreply@blogger.com0tag:blogger.com,1999:blog-1819822643050307843.post-76129799381005041852015-12-03T17:06:00.000+01:002017-12-03T17:20:22.588+01:00The Festival of Research 2015 was a great success!!The Navitas building on the Aarhus waterfront was buzzing with life as scientists from Aarhus University introduced their audience to the technologies of the future at the Festival of Research.<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjpvZbV7ZTa_5pS5tgiK2Woc9LQ_rDcPAG1KC8uPLjsxdqBEfWZd8RRT5yz7P6g37G84Yy1bRZ2zZKh62arnf_Hnr-O4fh9M5z_cUBJ-szVcIa3iYV_J87iTUD4jgZor7DESB55coAyvlM/s1600/vignet+1025x270.png" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" data-original-height="270" data-original-width="1025" height="105" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjpvZbV7ZTa_5pS5tgiK2Woc9LQ_rDcPAG1KC8uPLjsxdqBEfWZd8RRT5yz7P6g37G84Yy1bRZ2zZKh62arnf_Hnr-O4fh9M5z_cUBJ-szVcIa3iYV_J87iTUD4jgZor7DESB55coAyvlM/s400/vignet+1025x270.png" width="400" /></a></div>
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About 1,200 people took advantage of the opportunity to get a taste of the technologies of the future at the Festival of Research, which was held by Aarhus University on Friday 24 April 2015. Participants could listen to speed talks on topics like nanotechnology, 3D printers and telemedicine and take part in workshops and experiments in the lobby - including a special computer game that is helping scientists develop the quantum computer of the future. You could also take a tour of the Navitas building, courtesy of the Aarhus University School of Engineering.<br />
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhyEs-Xx3f8Z6aISficm9W6_ha233B_ADc_CQvO9auAftv5B6eJ8opr5yp4WKIC7FsbIsla-uY_86S3vzs6yxTsSdsqfA5PIz3c3dFCluT_EoFisyE8gNhAE_3nDE8mKADwxgtUWH_K7X0/s1600/csm_Forskningens_Doegn_LK_504_40615ef4dc.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" data-original-height="600" data-original-width="900" height="212" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhyEs-Xx3f8Z6aISficm9W6_ha233B_ADc_CQvO9auAftv5B6eJ8opr5yp4WKIC7FsbIsla-uY_86S3vzs6yxTsSdsqfA5PIz3c3dFCluT_EoFisyE8gNhAE_3nDE8mKADwxgtUWH_K7X0/s320/csm_Forskningens_Doegn_LK_504_40615ef4dc.jpg" width="320" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">A crowd of curious people attended the Festival of Research in the Navitas building. Photo: Lars Kruse, AU.</td></tr>
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<br />“There were lots of visitors to the Festival of Research, and the lecture halls and lobby area were full of people of all ages. Visitors were well-prepared and had checked events off in the programme, which had been distributed door-to-door, and the scientists meet a lot of interested, curious people,” said Charlotte Boel, project manager for the Festival of Research.</div>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgPNp3bcoMKPMQ1AHv45bJq1fCds7FEVeGlf0IiZ2SP42xkSblIFPK8BywwEBlPJvNp5m05JI0E7Pt43ldemIBicKDW1VAalNJNcPv6IB2DIPZz0kyMMxaPARg0zEgYhUNhLvSZBa0LZec/s1600/csm_IMG_6560_189626078f.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" data-original-height="600" data-original-width="400" height="320" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgPNp3bcoMKPMQ1AHv45bJq1fCds7FEVeGlf0IiZ2SP42xkSblIFPK8BywwEBlPJvNp5m05JI0E7Pt43ldemIBicKDW1VAalNJNcPv6IB2DIPZz0kyMMxaPARg0zEgYhUNhLvSZBa0LZec/s320/csm_IMG_6560_189626078f.jpg" width="212" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Photo: Lars Kruse, AU.</td></tr>
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As a new addition to this annual event, business people and upper secondary school students were invited to a special mid-morning presentation of the theme of the festival, the technologies of the future.<br />
I also contributed to the event with a speed talk introducing the importance of chirality in molecules. Below you can find the details.<br />
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Title: Molecules are also right and left-handed.</div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiwJLUQ-_Fpo6HlwQX621ind40Ww7RWdFd_FSgD1A2ZQ_Q8H7zNPZ9S7ripqI1pQ5W-_0j4rvQsdhyF46UTepgGy2MM9UcfNVXojqChA-ZQMHcNTE12KjuB1NiWVL2NEEimYqXYd2vVyXA/s1600/left-handed-molecules.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" data-original-height="235" data-original-width="350" height="214" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiwJLUQ-_Fpo6HlwQX621ind40Ww7RWdFd_FSgD1A2ZQ_Q8H7zNPZ9S7ripqI1pQ5W-_0j4rvQsdhyF46UTepgGy2MM9UcfNVXojqChA-ZQMHcNTE12KjuB1NiWVL2NEEimYqXYd2vVyXA/s320/left-handed-molecules.jpg" width="320" /></a></div>
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Summary:<br />
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Just as gloves and hands come in mirror-image pairs (a left and a right), many molecules can exist in ‘left-’ and ‘right-handed’ forms. This property of handedness is called chirality, and most biological molecules are chiral. Surprisingly, all living organisms contain almost only ‘left-handed’ amino acids and ‘right-handed’ sugars. This exclusive one-handedness has the important consequence that the biological and pharmaceutical activity of many molecules is often directly related to their chirality. Chemistry by means of the chiral synthesis favours the formation of a specific ‘left-’ and ‘right-handed’ molecules.<br />
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For more information about the event: <a href="http://newsroom.au.dk/en/news/show/artikel/forskningens-doegn-var-en-stor-succes/" target="_blank">http://newsroom.au.dk/en/news/show/artikel/forskningens-doegn-var-en-stor-succes/</a></div>
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Fernandohttp://www.blogger.com/profile/12522654073566755853noreply@blogger.com0tag:blogger.com,1999:blog-1819822643050307843.post-31761245677286712462015-09-01T20:30:00.000+02:002017-12-03T18:38:08.272+01:00Asymmetric catalysis: how it all started? 3 key experiments.<div style="text-align: justify;">
It is difficult to establish exactly when a new research area is born. Mainly due to the fact that scientific knowledge is generated continuously over the years since a scientist (or group of scientists) achieves a major breakthrough.</div>
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However, probably, we can agree that the asymmetric catalysis area was born in 1966. Of course, during the 1950s the introduction of X-Ray crystallography, which was used to determine the absolute configuration of an organic compound by Johannes Bijvoet in 1951 and the contribution of Klem and Reed who first reported the use of chirally-modified silica gel for chiral HPLC chromatographic separation are considered crucial for the analysis of chiral compounds and the further development of asymmetric catalysis during the 60s.</div>
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Independently, three different organic chemists, William S. Knowles (USA), Ryōji Noyori (Japan) and K. Barry Sharpless (USA) were the pioneers in the asymmetric catalysis area. For their contributions to this research area they received the 2001 Nobel Prize in Chemistry.</div>
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<tr><td class="tr-caption" style="text-align: center;">William S. Knowles: "I suspect that no invention has ever been made without some fortuitous help".</td></tr>
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Knowles and Noyori started working with the development of asymmetric hydrogenation, which they developed independently in 1968.</div>
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Basically, Knowles strategy consisted of replacing the achiral triphenylphosphine ligands in Wilkinson's catalyst ([RhCl(PPh3)3], used as a soluble hydrogenation catalyst for unhindered olefins) with chiral phosphine ligands. This chiral catalyst was employed in a hydrogenation reaction of α-phenylacrylic acid giving the final product with a modest 15% enantiomeric excess (ee).</div>
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This modest result was of no preparative value at that time. However, it established for the first time that by using a chiral catalyst the reaction course could be controlled to give an asymmetric bias on the final product. Further development of the chiral catalyst let control the enantioselectivity of the reaction efficiently. Knowles was also the first to apply asymmetric catalysis to industrial-scale synthesis; while working for the Monsanto Company and he developed an enantioselective hydrogenation step for the production of L-DOPA. This molecule is a precursor to neurotransmitters, e.g. dopamine, noradrenaline, and epadrenaline. As a drug, it is used in the clinical treatment of Parkinson's disease.</div>
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<tr><td class="tr-caption">Ryōji Noyori: "Our ability to devise straightforward and practical chemical syntheses is indispensable to the survival of our species."</td></tr>
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Noyori conceived a copper complex using a chiral Schiff base ligand, which he used for the metal-carbenoid cyclopropanation of styrene. Noyori's results for the enantiomeric excess for this first-generation ligand were disappointingly low: 6% ee. However, he continued developing this research that eventually led to the development of the Noyori asymmetric hydrogenation reaction.</div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgENmitnHHN6q7R8e-Bb6tB7qugsrNUqAD2Jc5asaeF_NQPQCO2ElF7Gbz3QbR1bLnTVcX0TOPGjkjZyAX41W7tddgxEW_LYQqh3lVX2C26WLYMtQHAUJ4dmTp_yXHZIgHlyqrmhGlixPI/s1600/noyori_scheme.png" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="278" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgENmitnHHN6q7R8e-Bb6tB7qugsrNUqAD2Jc5asaeF_NQPQCO2ElF7Gbz3QbR1bLnTVcX0TOPGjkjZyAX41W7tddgxEW_LYQqh3lVX2C26WLYMtQHAUJ4dmTp_yXHZIgHlyqrmhGlixPI/s400/noyori_scheme.png" width="400" /></a></div>
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Noyori also developed an asymmetric catalysis process at industrial scale in collaboration between Nagoya University and Takasago International Co. for the production of (-)-menthol.</div>
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<tr><td class="tr-caption">K. Barry Sharpless: "<span style="background-color: white; color: #252525; font-family: sans-serif; font-size: 14px; line-height: 22.4px; text-align: left;">.</span>..when I started doing chemistry I did it the way I fished – for the excitement, the discovery, the adventure, for going after the most elusive catch imaginable in uncharted seas".</td></tr>
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Sharpless complemented these reduction reactions by developing a range of asymmetric oxidations (the so-called Sharpless epoxidation, Sharpless asymmetric dihydroxylation, and Sharpless oxyamination during the 1970s to 1980's.</div>
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These initial experiments paved the way for subsequent developments that established asymmetric catalysis as one of the most powerful methods for the synthesis of chiral compounds.</div>
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Note: Part of the contents of this post has been extracted from Knowles, Noyori, and Sharpless Nobel Laurate Lectures. References below:</div>
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<i>Angew. Chem. Int. Ed.</i> <b>2002</b>, <i>41</i>, 1998.<br />
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<i>Angew. Chem. Int. Ed.</i> <b>2002</b>, <i>41</i>, 2008.</div>
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<i>Angew. Chem. Int. Ed.</i> <b>2002</b>, <i>41</i>, 2024.</div>
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Fernandohttp://www.blogger.com/profile/12522654073566755853noreply@blogger.com2tag:blogger.com,1999:blog-1819822643050307843.post-73177462225811462012015-07-01T09:00:00.000+02:002017-01-10T11:14:26.705+01:00Publication in Angewandte Chemie International Edition (this post is for specialists only)Recently, it has been published in Angewandte Chemie International Edition research I have been involved with my lab mates Line, Kim, and Sofie.<br />
For those who are familiar with organic chemistry, you will find the link to the original article below. Hope you enjoy reading it!<br />
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Næsborg, L., Halskov, K. S., Tur, F., Mønsted, S. M. N. and Jørgensen, K. A. (2015), Asymmetric γ-Allylation of α,β-Unsaturated Aldehydes by Combined Organocatalysis and Transition-Metal Catalysis. Angew. Chem. Int. Ed., 54: 10193–10197. doi: 10.1002/anie.201504749<br />
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<a href="http://onlinelibrary.wiley.com/doi/10.1002/anie.201504749/abstract" target="_blank">http://onlinelibrary.wiley.com/doi/10.1002/anie.201504749/abstract</a></div>
Fernandohttp://www.blogger.com/profile/12522654073566755853noreply@blogger.com0tag:blogger.com,1999:blog-1819822643050307843.post-84614229600231844792015-03-01T09:00:00.000+01:002015-12-06T19:11:17.613+01:00Then, why asymmetric catalysis?<div style="text-align: justify;">
In the previous posts, I have shown different approaches to access chiral compounds. Moreover, I stressed that the demand for chiral compounds, often as single enantiomers, has escalated sharply in recent years, driven particularly by the demands of the pharmaceutical industry, but also by other applications, including agricultural chemicals, flavours, fragrances, and materials. Two-thirds of prescription drugs are chiral, with the majority of new chiral drugs being single enantiomers. This widespread demand for chiral compounds has stimulated intensive research to develop improved methods for synthesizing such compounds.</div>
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So, then what is asymmetric catalysis and most important why is relevant for the synthesis of chiral compounds?</div>
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To get started, firstly, we should define the term asymmetric catalysis.</div>
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<u><b>Catalysis </b></u>is the increase in the rate of a chemical reaction due to the participation of an additional substance called a catalyst. By using a catalyst, the chemical reaction occur faster and require less activation energy. Because catalysts are not consumed after promoting the reaction, they can further catalyse the reaction of further quantities of reactant. Therefore, often only tiny amounts are required.</div>
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The term <b><u>asymmetric </u></b>when linked to catalysis refers to the phenomenon whereby a chiral catalyst promotes the conversion of an achiral substrate to a chiral product with a preference for the formation of one of the mirror image isomers (enantiomers).</div>
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In simple words, the rate of a chemical reaction is increased biasing the process towards the formation of just only one single enantiomer.</div>
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Historically, enantiomerically enriched compounds were generated either by chemical transformation of an enantiomerically enriched precursor, often derived directly or indirectly from nature's chiral pool, or by resolving an equimolar (racemic) mixture of the two enantiomers. Both of these approaches suffer from potentially severe drawbacks, the former in requiring stoichiometric amounts of a suitable precursor and the latter in typically yielding only up to 50% of the desired enantiomer.</div>
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Asymmetric catalysis, in which each molecule of chiral catalyst, by virtue of being continually regenerated, can yield many molecules of chiral product, has significant potential advantages over these older procedures. Indeed, enantiomerically pure compounds are produced in nature by such chirality transfer from enzymes.</div>
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Both from a conceptual and chemical efficiency point of view, the use of enantiomerically pure (chiral) catalysts instead of stoichiometric chiral auxiliaries is extremely attractive. Ideally, the final product can be obtained in a single step from a substoichiometric amount of chiral inductor (the catalyst) by transmission of the 3D information through organic reactions resulting in a chirality multiplication. In a prototype reaction a prochiral substrate (A) and an achiral reagent (R) react in the presence of a chiral catalyst to give an enantiomerically enriched (or pure) product (P*). The catalyst acts temporarily as a template coordinating starting products (A, R) transferring the chirality from the source of asymmetry to the new stereogenic centre created in the reaction (Figure 1).</div>
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Figure 1. Comparison of strategies based on chiral auxiliaries and chiral catalysts in asymmetric synthesis.</div>
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In the next posts, we will start a journey highlighting how far asymmetric catalysis has evolved and being considered one of the most prominent areas in organic chemistry.<br />
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Fernandohttp://www.blogger.com/profile/12522654073566755853noreply@blogger.com0tag:blogger.com,1999:blog-1819822643050307843.post-18252926681681891682015-02-28T11:54:00.000+01:002015-10-17T11:58:21.239+02:00How can we prepare a chiral compound? PART IV. Asymmetric synthesis.<div class="MsoNormal">
<span lang="EN-GB">In the
previous posts, (see how we can prepare a chiral compound? PART I to PART III, from
15 Dec 2014 onwards) I have shown different approaches to access chiral
compounds.<o:p></o:p></span></div>
<div class="MsoNormal" style="text-align: justify;">
<span lang="EN-GB">Although chiral resolution and chiral pool
synthesis have been used or are currently used as efficient methods for
preparing chiral compounds there is a high demand of new chiral compounds for
pharma, agrochemical, fragrances, fine chemicals and nutrition areas. This
means that even chiral pool (chiral compounds from Nature) and/or resolutions
are quite limited methods to address new challenging synthesis of chiral
compounds. Therefore, innovative approaches to overcome these limitations are desirable.<o:p></o:p></span></div>
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<span lang="EN-GB"><br /></span></div>
<div class="MsoNormal" style="text-align: justify;">
<span lang="EN-GB">The asymmetric (or stereoselective) synthesis
from prochiral substrates (i.e. substrates that will be chiral after a chemical
reaction) is a potent tool that allow the preparation of a broad variety of
enantiopure compounds.<o:p></o:p></span></div>
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<span lang="EN-GB">In order to fully understand the concept behind
asymmetric synthesis we have to review some definitions in organic chemistry
related to chirality:<o:p></o:p></span></div>
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<span lang="EN-GB"><br /></span></div>
<div class="MsoNormal" style="text-align: justify;">
</div>
<ul>
<li><b><u><span lang="EN-GB">Prochiral molecules</span></u></b><span lang="EN-GB"> are those that can be converted
from achiral to chiral in a single step (i.e. one single chemical reaction).</span></li>
<li><b><u><span lang="EN-GB">Stereoisomers</span></u></b><span lang="EN-GB"> are isomeric molecules (from Greek ἰσομερής,
isomerès; isos = "equal", méros = "part") that have the
same molecular formula and sequence of bonded atoms (constitution), but that
differ only in the three-dimensional orientation of their atoms in space.
Importantly, we can differentiate between enantiomers and diastereoisomers.</span></li>
<li><b><u><span lang="EN-GB">Enantiomers</span></u></b><span lang="EN-GB"> are two stereoisomers that are
mirror images of each other, which are non-superimposable. Two compounds that
are enantiomers of each other have the same physical properties.</span></li>
<li><b><u><span lang="EN-GB">Diastereomers</span></u></b><span lang="EN-GB"> are stereoisomers that are not
mirror images of each other. Diastereomers seldom have the same physical
properties.</span></li>
<li>Chemical reactions can be <b><u>stereoselective</u></b> which means that can be selectively directed
to one stereoisomer (enantio- or diastereoisomer) only.</li>
</ul>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiNBUkBbI8CnKnjofxrRKDEKSkwi4IMulM05VvyZd_hqog7qw2Dk_qtzfbn-TNsI4Dg0rX1hRyi1xswfu1nav0pthFbMaRGfzwDmdsc0KblVDv-3iC081ub6BMO4nCdH1F1RDRpmlfFvgU/s1600/fig1.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="232" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiNBUkBbI8CnKnjofxrRKDEKSkwi4IMulM05VvyZd_hqog7qw2Dk_qtzfbn-TNsI4Dg0rX1hRyi1xswfu1nav0pthFbMaRGfzwDmdsc0KblVDv-3iC081ub6BMO4nCdH1F1RDRpmlfFvgU/s400/fig1.jpg" width="400" /></a></div>
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<span lang="EN-GB">Once we have a clear-cut picture of these
definitions it is important to highlight that asymmetric synthesis involves
chemical reactions that introduce one or more elements of chirality in a prochiral
substrate generating stereoisomeric compounds (enantio- or diastereoisomers) in
unequal amounts. The responsible for the asymmetric induction is the so-called
chiral auxiliary (or chiral catalyst in the case of the asymmetric catalysis approach
I am going to explain in next posts).<o:p></o:p></span></div>
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<span lang="EN-GB"><br /></span></div>
<div class="MsoNormal" style="text-align: justify;">
<span lang="EN-GB">A <b>chiral
auxiliary</b> is a chemical compound that is temporarily incorporated into an
organic molecule in order to control the stereochemical outcome of the reaction.
In simple words, we install a chiral molecule that “help” us to obtain our
target compound.<o:p></o:p></span></div>
<div class="MsoNormal" style="text-align: justify;">
<span lang="EN-GB">The asymmetric synthesis methods have evolved
during the years. Early methods for asymmetric synthesis introduced the chiral auxiliary
in the same molecule to be transformed, generating the chiral product
permanently attached to the group responsible for asymmetric induction (<b>diastereoselective synthesis</b>). Then,
the methods further developed to those that remove the chiral auxiliary from
the final chiral product and preferably recover and reuse the chiral auxiliary
in future reactions.<o:p></o:p></span></div>
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<span lang="EN-GB">The first step involves the incorporation
of the chiral auxiliary. From a proquiral compound we move to a stereoisomer.
Then, a second chemical reaction is carried out on the stereoisomer. The
chirality present in the auxiliary can bias the stereoselectivity of this
reaction towards one diastereoisomer only (diastereoselective synthesis). Finally,
the chiral auxiliary can then be cleaved from the substrate and is typically
recovered for future uses, ideally, without any loss of performance during the
diastereoselective reaction.<o:p></o:p></span></div>
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<span lang="EN-GB"><br /></span></div>
<div class="separator" style="clear: both; text-align: center;">
<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg90lsnDm4Y4qu-rUn6isdZpruAtJydgnw0mLTQEvJ5aJFunPVdXOoEVTo2Az4D_L6cqBvCkKj_uDVlivZThHtWgVXTSvHipftVGfgFPZzbGFJLhM91iL04TtxaFtctyVWax7Tpyl4M6BQ/s1600/chiral+auxiliary.png" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="141" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg90lsnDm4Y4qu-rUn6isdZpruAtJydgnw0mLTQEvJ5aJFunPVdXOoEVTo2Az4D_L6cqBvCkKj_uDVlivZThHtWgVXTSvHipftVGfgFPZzbGFJLhM91iL04TtxaFtctyVWax7Tpyl4M6BQ/s400/chiral+auxiliary.png" width="400" /></a></div>
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<span lang="EN-GB"><br /></span></div>
<div class="MsoNormal" style="text-align: justify;">
<span lang="EN-GB">The next step was to use a chiral reagent
(instead of the so-called auxiliary) and directly control the stereochemical
outcome of the reaction. </span>Nowadays, it is used a chiral catalyst to control the stereochemical outcome of the reaction.</div>
Fernandohttp://www.blogger.com/profile/12522654073566755853noreply@blogger.com3tag:blogger.com,1999:blog-1819822643050307843.post-73050256072435683002015-01-31T09:00:00.000+01:002017-12-03T16:42:34.672+01:00How can we prepare a chiral compound? PART III. Chiral pool synthesis.<div style="text-align: justify;">
In the previous post (see post How can we prepare a chiral compound? PART II, 31 Dec 2014) I have shown that one of the main approaches to access chiral compounds is the chiral resolution of racemic mixtures.</div>
<div style="text-align: justify;">
Another alternative available for obtaining chiral compound is carrying out synthetic transformations from an enantiomerically pure starting compound. In the specific case of using simply available natural compounds as starting materials, it is called <b><u>chiral pool synthesis</u></b>. This method is particularly interesting when the desired final product and the chiral compound used as starting material are structurally similar, i.e. the chiral natural product as starting material is wholly or partially built into the target molecule.<br />
The main compounds from the chiral pool that have been used for this purpose are α-amino acids, hydroxyacids, carbohydrates and terpenes. These natural compounds have some advantageous properties: their optical purity is normally close to 100% they are in general non-toxic and many are inexpensive starting materials.</div>
<div style="text-align: justify;">
However, this strategy may not be especially helpful if the desired molecule does not bear a great resemblance to inexpensive enantiopure natural products. Otherwise, a long, probably difficult synthesis involving many steps may be required. In addition, it may be challenging to find a suitable enantiopure starting material, so other approaches may prove more fruitful.</div>
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<b><span lang="EN-GB"><br /></span></b></div>
<div class="MsoNormal">
<b><span lang="EN-GB"><u>Organic chemistry is like playing with Lego®</u><o:p></o:p></span></b></div>
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<span lang="EN-GB"><br /></span></div>
<div>
There is a high demand for ready access to chiral drugs in the pharma industry and chiral pool synthesis has been used for this purpose in some of the current well-known drugs.<br />
Organic chemistry bring us the possibility to mimic Nature in order to have access to these natural compounds (with therapeutic properties) or modified and improved efficacy compounds. Easily and giving an example linked to our daily lives, organic synthesis resembles playing Lego®. Organic chemists have a huge toolbox filled with small Lego® bricks (our building blocks). Smart combination and assembly of these Lego® bricks let us to build up more complex structures (our targeted drug). In particular, the chiral pool synthesis rummages in Nature to find these tiny chiral blocks that fit the complex structure we want to build up by means of chemical reactions.</div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEimg2w_PXdRNlRmrx6KvFyFx8tkWSmYrOkaExnJgK74e9r6x2RMkalBTyUDMAFuxSA8L6s9lCognbm-7Kj4UFBqtjOvY0kbnxQNITL0x8pNg-EaAYI6yZislglvDKi0DvfStdUFZ1nb_34/s1600/fig1.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="165" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEimg2w_PXdRNlRmrx6KvFyFx8tkWSmYrOkaExnJgK74e9r6x2RMkalBTyUDMAFuxSA8L6s9lCognbm-7Kj4UFBqtjOvY0kbnxQNITL0x8pNg-EaAYI6yZislglvDKi0DvfStdUFZ1nb_34/s1600/fig1.jpg" width="400" /></a></div>
<div>
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<b><span lang="EN-GB"><br /></span></b></div>
<div class="MsoNormal" style="text-align: justify;">
<b><u>Chiral pool synthesis</u></b> is a strategy that aims to improve the efficiency of organic synthesis. It starts the synthesis of a complex enantiopure chemical compound from a stock of readily available enantiopure substances. Let me have a look to two examples of chiral pool synthesis to illustrate the usefulness of this methodology. </div>
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The drug <u>Imipenem</u> is a beta-lactam antibiotic for intravenous use administered in hospitals for the treatment of several bacterial infections. It is on the World Health Organization's List of Essential Medicines, a list of the most important medications needed in a basic healthcare system. It was discovered by Merck scientists when searching for a more stable version of the natural product thienamycin, which is produced by bacterium.</div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiktQEXFVnjM74UCF2uRvLlfZDMWNV8261JHzs_OjpCZJWWIQPhGr_64UO43rupnBUATnFBiq_RYn2vz4SYixXD3RskPtenhYt8De1MLOg4nJTtQioEqVONGpB7zapbblki2GHaV35SDsU/s1600/fig1_2.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="115" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiktQEXFVnjM74UCF2uRvLlfZDMWNV8261JHzs_OjpCZJWWIQPhGr_64UO43rupnBUATnFBiq_RYn2vz4SYixXD3RskPtenhYt8De1MLOg4nJTtQioEqVONGpB7zapbblki2GHaV35SDsU/s1600/fig1_2.jpg" width="400" /></a></div>
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The pharma company Merck markets the drug Imipenem (in combination with cilastatin to enhance its therapeutic effect) under the trade names Primaxin® or Tienam®. The synthesis of Imipenem is carried out by using aspartic acid as starting material. Aspartic acid is one of the 20 existing natural aminoacids present in Nature (our chiral pool) commonly used in chiral pool synthesis due to its ready availability, low cost and simple structure. From aspartic acid through several chemical reactions the structure of Imipenem is built up (highlighted in red the fragment coming from the starting material incorporated into the final molecule).</div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhJQh1WvwfAVPoHcSP7PUjOA5OXvSI0HcCzKT04-pVQvSKaPPnMAfBarrjz3qUYEJcgV7_CFMx7iM06Ss-duAsjwS2NPLmQOY4UcDJsfDbPC3MQgi_vaX8jDm7OyaUJM0RnhXGwpBAIRCw/s1600/fig1_3.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="116" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhJQh1WvwfAVPoHcSP7PUjOA5OXvSI0HcCzKT04-pVQvSKaPPnMAfBarrjz3qUYEJcgV7_CFMx7iM06Ss-duAsjwS2NPLmQOY4UcDJsfDbPC3MQgi_vaX8jDm7OyaUJM0RnhXGwpBAIRCw/s1600/fig1_3.jpg" width="400" /></a></div>
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The drug <u>Oseltamivir </u>is marketed under the trade name Tamiflu® by the pharma company Hoffmann-La Roche. It is an antiviral medication used to prevent and treat influenza A and influenza B (flu). It is also on the World Health Organization's List of Essential Medicines. Its commercial production starts from the molecule shikimic acid harvested from Chinese star anise (<i>Illicium verum</i>) with a limited worldwide supply (highlighted in red the fragment coming from the starting material incorporated into the final molecule).</div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEj1gEXe1-QtGMgPG4_DonuG6VFNMcHNLlCvzr2a6jeIFBxay7w_sqInENheOPkDb7KWKA4DWQbI3qNXU8FlHon7aUsMRBb097Atl_iyiH_Ho0CIhtElu4AjW-6xSu__mPdze5M2HKRtL-o/s1600/fig1_4.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="162" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEj1gEXe1-QtGMgPG4_DonuG6VFNMcHNLlCvzr2a6jeIFBxay7w_sqInENheOPkDb7KWKA4DWQbI3qNXU8FlHon7aUsMRBb097Atl_iyiH_Ho0CIhtElu4AjW-6xSu__mPdze5M2HKRtL-o/s1600/fig1_4.jpg" width="400" /></a></div>
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<div style="text-align: justify;">
Due to the limited supply of shikimic acid, searches for alternative synthetic routes preferably not requiring shikimic acid are underway and to date several other alternatives routes have been proposed.<br />
Both examples, Imipenem and Oseltamivir, show us how we can take advantatge of the chiral pool for obtaining chiral drugs very useful for treating diseases.</div>
</div>
Fernandohttp://www.blogger.com/profile/12522654073566755853noreply@blogger.com2tag:blogger.com,1999:blog-1819822643050307843.post-57506087804314820352014-12-31T09:00:00.000+01:002015-01-02T16:12:46.910+01:00How can we prepare a chiral compound? PART II. Resolution of racemates.<div style="text-align: justify;">
As shown in the previous post (see how can we prepare a chiral compound? PART I, 15 Dec 2014) one of the main approaches to access chiral compounds is the so-called chiral (or optical, or classical) resolution of racemic mixtures.</div>
<div style="text-align: justify;">
The <b>classical resolution</b> involves the physical separation of the pair of enantiomers contained in a racemic mixture (i.e. a 50/50 mixture of both enantiomers). The isolation of one of the enantiomer from the racemic mixture is achieved by using a physical method (e.g. crystallization) combined with a chemical reaction in some cases.</div>
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<b><u>Obtaining chiral compounds with tweezers!</u></b></div>
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<div style="text-align: justify;">
Louis Pasteur performed the first optical resolution in 1848, and was able to manually separate two kinds of crystals of racemic tartaric acid salts by using magnifying glasses and tweezers. This fact represented the discovery of molecular chirality and the <b>spontaneous resolution</b>. The process consists of crystallizing a supersaturated solution of racemic sodium ammonium tartrate below 28 ºC. Then, he was able to identify the different shapes of the crystals for each enantiomer. In this case, there is no chemical reaction involved in the resolution. In spite of the simplicity of this separation technique, it is limited to <b>conglomerates</b>. In fact, just only 5-10% of all racemates are known to crystallize as mixtures of enantiopure crystals.</div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiEEsC0QpDUNDawL748ajy-TReWlJXHoPIaTciVNa_UhWUH7390tGbtX_OZMjT1KbsaMdt9aSk8_9kosykreTdM2GlchRP112u1aH_WkW8z9j9xqD6u4LZ9D02way9swTev7BOiDFdpGf0/s1600/fig11.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiEEsC0QpDUNDawL748ajy-TReWlJXHoPIaTciVNa_UhWUH7390tGbtX_OZMjT1KbsaMdt9aSk8_9kosykreTdM2GlchRP112u1aH_WkW8z9j9xqD6u4LZ9D02way9swTev7BOiDFdpGf0/s1600/fig11.jpg" /></a></div>
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Another interesting process is the so-called <b>preferential crystallization</b> (also called <b>resolution by entrainment</b>). Again, Pasteur in 1882 demonstrated that by seeding a supersaturated solution of sodium ammonium tartrate with one of its enantiomers crystallized preferably the same enantiomer he used as a seed.</div>
<div style="text-align: justify;">
Again, there is no chemical reaction involved; we just only take advantage of the different solubility of one enantiomer compared to the other. This means that the crystallization rate of one enantiomer is faster than the other one, crystallizing out from the solution. The microscopic nature of the process of crystallization let us identify that in some specific examples enantiomers can self-recognize better than recognize each other yielding the pure enantiomers in the solid state separately.</div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhLAe3FDKhc4vIACTUIxDhRz6rBECtYeL1Fj1NtS-TiOwwyhTzI5dQRB3wbvSbJ4oB0rtJbBWmKshmeh5w8vhf09j7_pDrwFDX10MN2RrbVkbVrgNaKkuKx2l56sJOYoW70CgHhgdR4uBI/s1600/fig12.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhLAe3FDKhc4vIACTUIxDhRz6rBECtYeL1Fj1NtS-TiOwwyhTzI5dQRB3wbvSbJ4oB0rtJbBWmKshmeh5w8vhf09j7_pDrwFDX10MN2RrbVkbVrgNaKkuKx2l56sJOYoW70CgHhgdR4uBI/s1600/fig12.jpg" /></a></div>
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Crystallization of conglomerates and resolution by entrainment are reliable processes for the obtention of chiral compounds at the pharma industry mainly because they are easy and economical to implement and scale-up. However, the maximum yield for these processes is 50% (we "lose" the enantiomer we are not interested in) . In addition, our chiral compound of interest should crystallize as conglomerate and as stated above this is restricted to ca. 10% of chiral compounds.</div>
<br />
<b><u>Crystallization of diastereomeric salts</u></b><br />
<br />
<div style="text-align: justify;">
Notably, the vast majority of resolutions involve the conversion of a racemate, by treatment with an enantiomer of a chiral substance (the so-called chiral resolving agent), into diastereomeric salts. Diastereoisomers differ from enantiomers that the latter have the same physical properties. The different solubility of diastereoisomers allow the separation of both products and subsequent treatment with an acid or a base give access to both pure enantiomers. Derivatization to diastereoisomers is possible by salt formation between an amine and a carboxylic acid. The method was introduced (again) by Louis Pasteur in 1853 by resolving racemic tartaric acid with optically active (+)-cinchotoxine.</div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiq5TujkasFbX8Kr3X1XcZsEHFJzsSDZFJ2ayMfK8L9AS-srv_shoFKCSRgFtwUnxq-alhFOcK5A4xivKlJSXYaFdPbdOnALVRAOFVCTvVbcJYqg2QcZptm00qnfj95kBE4gI9ivvhKvTQ/s1600/fig13.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiq5TujkasFbX8Kr3X1XcZsEHFJzsSDZFJ2ayMfK8L9AS-srv_shoFKCSRgFtwUnxq-alhFOcK5A4xivKlJSXYaFdPbdOnALVRAOFVCTvVbcJYqg2QcZptm00qnfj95kBE4gI9ivvhKvTQ/s1600/fig13.jpg" height="320" width="270" /></a></div>
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The use of this method circumvents the issue of crystallization as conglomerate, and allows the use of a broad range of chiral resolving agents from the chiral pool. Even chiral synthetic reagents increase the options of finding the most suitable chiral substance to react with our enantiomer of interest. It is considered the most traditional method of resolving racemates, also easily implemented in the chemical industry. However, we still keep the maximum chemical yield for this process up to 50%.</div>
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<b><u>Towards the "perfect" chiral resolution</u></b></div>
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<br /></div>
<div style="text-align: justify;">
Apart from the aforementioned classical resolution process based on physical properties like solubility there are other resolution processes that can led to the separation of both enantiomers with yields above the 50%, ideally up to 100%.</div>
<div style="text-align: justify;">
As opposed to chiral resolution, <b>kinetic resolution</b> (KR) does not rely on different physical properties of diastereomeric products, but rather on the different chemical properties of the racemic starting materials.</div>
<div style="text-align: justify;">
In particular, kinetic resolution relies on the different reaction rate of the enantiomers with a chiral non racemic reagent. In this case, the reaction rates should differ enough to recover the less reactive or non-reactive enantiomer. The maximum chemical yield for this process is 50% for each enantiomer and one of them is chemically modified. Kinetic resolution reactions utilizing purely synthetic reagents and catalysts are less common than the use of enzymes although a number of useful synthetic catalysts have been developed achieving excellent performances.</div>
<div style="text-align: justify;">
Again, Louis Pasteur accomplished the first reported kinetic resolution. After reacting aqueous racemic ammonium tartrate with a mold from Penicillium glaucum, he reisolated the remaining tartrate and found it was enantiomerically pure. The chiral microorganisms present in the mold catalyzed the reaction of (<i>R</i>,<i>R</i>)-tartrate selectively, leaving an excess of (<i>S</i>,<i>S</i>)-tartrate.</div>
<div style="text-align: justify;">
<br /></div>
<div style="text-align: justify;">
As you can observe from the methods above the maximum chemical yield for the enantiomer of interest is 50%. In order to avoid this “loss” of material there is a type of kinetic resolution called <b>dynamic kinetic resolution</b> (DKR) where 100% of a racemic compound can be converted into an enantiopure compound. The same principles of KR applies to DKR. In addition, DKR utilizes a chemical reaction to interconvert the (R) and (S) enantiomers throughout the reaction process (this is called epimerization). At this point, the catalyst can selectively react with a single enantiomer, leading to almost 100% chemical yield.</div>
<div style="text-align: justify;">
<br /></div>
<div class="separator" style="clear: both; text-align: center;">
<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjVXqehWGxMyIcK11r1spHMVExtYMe60ZkboMFmS8-2KJUJzt5NbvfhWI_lJmSJpphAXRoX7h01JwUZ4uZrEnVV6Ul6OBxiTKVPNy2KYfm664LySatAzdOwdqLHXIsVwacGKcaKufcpj10/s1600/fig14.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjVXqehWGxMyIcK11r1spHMVExtYMe60ZkboMFmS8-2KJUJzt5NbvfhWI_lJmSJpphAXRoX7h01JwUZ4uZrEnVV6Ul6OBxiTKVPNy2KYfm664LySatAzdOwdqLHXIsVwacGKcaKufcpj10/s1600/fig14.jpg" /></a></div>
<div style="text-align: justify;">
<br /></div>
<div style="text-align: justify;">
It is necessary to consider the practicality of utilizing resolutions (classical or kinetic ones) for the preparation of enantiopure products. Even for a chiral molecule, which can be attained through other methods, the racemate may be significantly less expensive than the enantiopure material, resulting in heightened cost-effectiveness even with the inherent "loss" of 50% of the material. The main important aspects to evaluate the effectiveness of these methodologies are: </div>
<div style="text-align: justify;">
<ul>
<li>Inexpensive racemate (and chiral catalyst in KR, DKR). </li>
<li>No appropriate enantioselective synthesis available. </li>
<li>Straightforward separation of starting material and the target enantiomer. </li>
<li>Resolution proceeds selectively at low catalyst loadings (i.e. using small amounts of catalyst).</li>
</ul>
</div>
<div style="text-align: justify;">
To date, a number of catalysts for kinetic resolution have been developed that satisfy most, if not all of the above criteria, making them highly practical for use in organic synthesis of chiral compounds.</div>
Fernandohttp://www.blogger.com/profile/12522654073566755853noreply@blogger.com1tag:blogger.com,1999:blog-1819822643050307843.post-62189918499047377332014-12-15T09:00:00.000+01:002017-01-16T16:38:34.335+01:00How can we prepare a chiral compound? PART I<div class="MsoNormal" style="text-align: justify;">
<span lang="EN-GB">In past blog entries I have shown that
chirality is an important property of molecules. In molecules intended to be
used as drugs, chirality may be extremely important since the biological effect
directly depending on the stereochemistry of the compound (e.g. the thalidomide).</span><br />
<span lang="EN-GB">The administration
of enantiopure drugs brings benefits in terms of improved efficacy, and reduced
toxicity. Consequently, it is not strange that 7 out of the top 10 most
selling-drugs worldwide in 2010 are commercialized as enantiopure forms. <o:p></o:p></span>Therefore, it is relevant to have synthetic methods to access these chiral compounds obtaining just only the enantiomer we are interested in.</div>
<div class="MsoNormal" style="text-align: justify;">
<span lang="EN-GB"><br /></span></div>
<div class="MsoNormal">
<span lang="EN-GB"><b><u>Let’s "cook" chiral molecules!</u></b><o:p></o:p></span></div>
<div class="MsoNormal">
<span lang="EN-GB"><br /></span></div>
<div class="MsoNormal" style="text-align: justify;">
The
synthesis of chiral compounds is addressed by an area of chemistry called
enantioselective synthesis. Simply: it is the synthesis of a compound by a
method that favours the formation of a specific enantiomer. Enantioselective
synthesis is a key process in modern chemistry and is particularly important in
the field of pharmaceuticals. It has also a prominent role in the food,
agrochemical, and perfumery industries.</div>
<div class="MsoNormal" style="text-align: justify;">
<br /></div>
<div class="separator" style="clear: both; text-align: center;">
<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjWi2kygZuixwHXlJIjVKE6ys_epFYbYsrsuTuQ2Sbx9qO8dA4CyCCHWqBZgJ4ct1Keq5Tfi4-8lZItF5xSGfOcdd1Smqb5PEPTy-3FKmnIOfsarTXqy-GUY6P60QgqQnTGJvRVG88Gil8/s1600/Chemistry-enthusiast.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="212" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjWi2kygZuixwHXlJIjVKE6ys_epFYbYsrsuTuQ2Sbx9qO8dA4CyCCHWqBZgJ4ct1Keq5Tfi4-8lZItF5xSGfOcdd1Smqb5PEPTy-3FKmnIOfsarTXqy-GUY6P60QgqQnTGJvRVG88Gil8/s1600/Chemistry-enthusiast.jpg" width="320" /></a></div>
<div class="MsoNormal" style="text-align: justify;">
<br /></div>
<div class="MsoNormal" style="text-align: justify;">
<span lang="EN-GB">On the other hand, we must recognize that the
social demands on the current chemistry are increasingly higher. Selectivity should
be applied to every single stage of chemical production. It is useless to
produce the enantiomer with no biological effect (and/or toxic effects). In
fact, it is considered waste, so it is worth focusing on obtaining the useful
enantiomer only. Chemical waste is not a trivial issue considering that usually
chemical synthesis is scaled-up (e.g. production of pharmaceuticals or
agrochemicals) and this may be very costly in industrial processes where the
economic aspects are crucial.<o:p></o:p></span><br />
<span lang="EN-GB"><br /></span></div>
<div class="MsoNormal" style="text-align: justify;">
<span lang="EN-GB"><b>Chirality cannot be created in molecules by a
random chemical process.</b> When a random chemical reaction is used to prepare
molecules having chirality, there is an equal opportunity to prepare the
left-handed isomer as well as the right-handed isomer. In addition, and more
relevant, the preferential formation in a chemical reaction of one enantiomer
over the other is result of the influence of a chiral feature present in the
substrate, reagent, catalyst or environment. Chemical synthesis of a chiral
molecule from simpler non-chiral precursors usually produces equal amounts of
both enantiomers. For this reason, <b>we strictly need a source of chirality</b>.<o:p></o:p></span></div>
<div class="MsoNormal">
<span lang="EN-GB"><br /></span></div>
<div class="MsoNormal">
<span lang="EN-GB">The three
main approaches to access chiral compounds are:<o:p></o:p></span></div>
<div class="MsoNormal">
<span lang="EN-GB"><br /></span></div>
<div class="MsoNormal">
<span lang="EN-GB"><u>Chiral (or
optical) resolution of racemic mixtures:</u><o:p></o:p></span></div>
<div class="MsoNormal">
<span lang="EN-GB"><u><br /></u></span></div>
<div class="MsoNormal" style="text-align: justify;">
<span lang="EN-GB">Namely, physical separation of the pair of
enantiomers contained in a 50/50 mixture. This involves the isolation of one
enantiomer from the racemic mixture by any of a number of methods. Where the cost
in time and money of making such racemic mixtures is low, or if both
enantiomers may find use, this approach may remain cost-effective.<o:p></o:p></span></div>
<div class="MsoNormal" style="text-align: justify;">
<span lang="EN-GB"><br /></span></div>
<div class="separator" style="clear: both; text-align: center;">
<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhH9TuemfBaTFTggj4CpHORGEsr7m635mv-4mkRAGFu8vA8S36-ky14F9FWeJanGbxAkE0thbK6kR2hFn-fwyO50IsHaj-lLnsp9ZLO_fm-6ODUysc63sT2oCMH_bytkG12AaHkT3f25pI/s1600/fig8.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhH9TuemfBaTFTggj4CpHORGEsr7m635mv-4mkRAGFu8vA8S36-ky14F9FWeJanGbxAkE0thbK6kR2hFn-fwyO50IsHaj-lLnsp9ZLO_fm-6ODUysc63sT2oCMH_bytkG12AaHkT3f25pI/s1600/fig8.jpg" /></a></div>
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<span lang="EN-GB"><br /></span></div>
<div class="MsoNormal" style="text-align: justify;">
<span lang="EN-GB"><br /></span></div>
<div class="MsoNormal">
<span lang="EN-GB"><u>Synthetic
transformations from an enantiomerically pure starting compound:</u><o:p></o:p></span></div>
<div class="MsoNormal">
<span lang="EN-GB"><br /></span></div>
<div class="MsoNormal">
<div style="text-align: justify;">
<span lang="EN-GB">In the
particular case of using an easily available natural compound as starting material it is called chiral
pool synthesis. This methodology is more useful when the desired final product and
the chiral compound used are structurally similar. Carbohydrates, amino acids,
hydroxy acids and terpenes integrate the chiral pool arsenal.<o:p></o:p></span></div>
</div>
<div class="MsoNormal">
<span lang="EN-GB"><br /></span></div>
<div class="separator" style="clear: both; text-align: center;">
<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEi420omoqWTiq57_1DrZZ6Upt6ISAJWMnu5H01PZEaQdbASkJXI3nLGVAEVFR_m246ylZ93alou47RlFC0eBi5Ma-f-H5ccKzK5820dUHrEabhyPuIOO12xqLTr8SUHal01nSOz4tTr_Wk/s1600/fig9.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEi420omoqWTiq57_1DrZZ6Upt6ISAJWMnu5H01PZEaQdbASkJXI3nLGVAEVFR_m246ylZ93alou47RlFC0eBi5Ma-f-H5ccKzK5820dUHrEabhyPuIOO12xqLTr8SUHal01nSOz4tTr_Wk/s1600/fig9.jpg" /></a></div>
<div class="MsoNormal">
<span lang="EN-GB"><br /></span></div>
<div class="MsoNormal">
<span lang="EN-GB"><br /></span></div>
<u>Stereoselective synthesis:</u><br />
<div>
<br /></div>
<div>
This approach involves the use of a prochiral substrate and an enantiopure reagent as a source of chirality, in stoichiometric (auxiliary) or substoichiometric (catalytic) amounts, which is not included in the final product.</div>
<div>
<br /></div>
<div class="separator" style="clear: both; text-align: center;">
<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgag_yQjkJWE2GhsjL2a1zx0BR_W7c_yiHRWTb2w1AklnDFPA1YzvYVHb1AWr31JzeViZJCpt3AWvQGRciMti5b6rl9IRV-ndlYXcapBgVMKL_tcsI_Y1mfA-Fe-wnEsSlCMPos2yLcmps/s1600/fig10.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgag_yQjkJWE2GhsjL2a1zx0BR_W7c_yiHRWTb2w1AklnDFPA1YzvYVHb1AWr31JzeViZJCpt3AWvQGRciMti5b6rl9IRV-ndlYXcapBgVMKL_tcsI_Y1mfA-Fe-wnEsSlCMPos2yLcmps/s1600/fig10.jpg" /></a></div>
<div class="separator" style="clear: both; text-align: justify;">
<br /></div>
<div class="separator" style="clear: both; text-align: justify;">
In the next blog entries we are going to have a close look to these three different approaches to have access to chiral compounds highlighting pros and cons of each method.</div>
Fernandohttp://www.blogger.com/profile/12522654073566755853noreply@blogger.com0tag:blogger.com,1999:blog-1819822643050307843.post-42758096000549437672014-12-01T09:00:00.000+01:002014-12-01T09:00:07.982+01:00The thalidomide disaster and why chirality is important in drugs.<div class="MsoNormal">
<div style="text-align: justify;">
<span lang="EN-GB">In past
blog entries I have shown that enantiomers are optical isomers which are
nonsuperimposable mirror-image structures. A mixture of equal portions (50/50)
of the (+) and (-) enantiomers is called a racemic mixture. The chirality of a
compound is very important when interacting with a chiral medium as the human
body, the biological effect directly depending on the stereochemistry of the compound
and the receptor in the body. Thus, a single-enantiomer drug can be pharmacologically
interesting whereas its mirror image can be inactive or display a different
desirable or non-desirable activity.<o:p></o:p></span></div>
</div>
<div class="MsoNormal">
<div style="text-align: justify;">
<span lang="EN-GB">The
thalidomide disaster is one of the darkest episodes in pharmaceutical research
history. Chirality of molecules played a crucial role in this story and underscored
its importance in organic synthesis of pharmaceuticals.<o:p></o:p></span></div>
</div>
<div class="MsoNormal">
<div style="text-align: justify;">
<span lang="EN-GB">In 1957, a
pharmaceutical company in West Germany introduced a new drug to the market. It
was called thalidomide. The drug was sold in several countries as a sedative
and sleeping drug for pregnant women. The thalidomide is a chiral molecule. However,
the drug was made and marketed as a racemic mixture of the (+)-(<i>R</i>)-thalidomide and (-)-(<i>S</i>)-thalidomide.<o:p></o:p></span></div>
</div>
<div class="MsoNormal">
<span lang="EN-GB"><br /></span></div>
<div class="separator" style="clear: both; text-align: center;">
<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg1oMwqYWQbXy2nSLWIQnPXWY_8v-BkdFOcoL9dmy5WjzGL3XFltd3gULRVAm2RtWZ2XVJyRtHpIjW8QQ_d8X98y88B4qGifSQjDcWmwsEzBXvhAh9YQZInRzbQMdnHXuDHLTcECRqsW6w/s1600/fig7.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg1oMwqYWQbXy2nSLWIQnPXWY_8v-BkdFOcoL9dmy5WjzGL3XFltd3gULRVAm2RtWZ2XVJyRtHpIjW8QQ_d8X98y88B4qGifSQjDcWmwsEzBXvhAh9YQZInRzbQMdnHXuDHLTcECRqsW6w/s1600/fig7.jpg" height="71" width="320" /></a></div>
<div class="MsoNormal">
<span lang="EN-GB"><br /></span></div>
<div class="MsoNormal">
<span lang="EN-GB"><br /></span></div>
<div class="MsoNormal">
<div style="text-align: justify;">
Tragically,
thalidomide was found to have serious side-effects; thousands of babies were
born with missing or abnormal arms, hands, legs, or feet. It was banned by many
countries in 1961. Nowadays scientists know that it is the (-)-(<i>S</i>)-thalidomide that caused the severe
side-effects. (+)-(<i>R</i>)-thalidomide is
a sedative, but (-)-(<i>S</i>)-thalidomide
is a teratogen (i.e., a drug that can harm a foetus in the womb).</div>
</div>
<div class="separator" style="clear: both; text-align: center;">
<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEikhyphenhyphendxBLrPvcEHUmXGIGV4m2GDAX9IZM6HkdqLbswNmaDA3m576C-ELWlY-uLZrf7eDjgA_wiTD8rvsaajRxaQiuKZKv1YnUrEjB6Ebb6-0olHb0dpmEvQfPAeJl8mO0z5IPuXIc1fuYQ/s1600/foetus.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEikhyphenhyphendxBLrPvcEHUmXGIGV4m2GDAX9IZM6HkdqLbswNmaDA3m576C-ELWlY-uLZrf7eDjgA_wiTD8rvsaajRxaQiuKZKv1YnUrEjB6Ebb6-0olHb0dpmEvQfPAeJl8mO0z5IPuXIc1fuYQ/s1600/foetus.jpg" /></a></div>
<div class="MsoNormal">
<span lang="EN-GB"><br /></span></div>
<div class="MsoNormal">
<div style="text-align: justify;">
Thus, (-)-(<i>S</i>)-thalidomide is the unwanted
enantiomer. You might think that pharma companies can simply purify the racemic
mixture and give patients only the (+)-(<i>R</i>)-thalidomide.
Unfortunately, the answer is not that simple in this specific case. Human liver
contains an enzyme that can convert (+)-(<i>R</i>)-thalidomide
to (-)-(<i>S</i>)-thalidomide. Therefore,
even administration of enantiomerically pure (+)-(<i>R</i>)-thalidomide results in a racemic mixture. It is said that in the
human body thalidomide undergoes racemization.</div>
</div>
<div class="MsoNormal">
<div style="text-align: justify;">
<span lang="EN-GB">This
disaster was a driving force behind requiring strict testing of drugs before
making them available to the public. Now there is rigorous testing before
launching new drugs into the market. The ban of thalidomide was lifted in 1985
by the World Health Organization. Today, thalidomide is used experimentally in
all continents to treat various cancers and inflammatory diseases.<o:p></o:p></span></div>
</div>
<div>
<div style="text-align: justify;">
<br /></div>
</div>
<div style="text-align: justify;">
Despite of the fact of the racemization of thalidomide in the body, this example illustrates the importance of obtaining just only one single enantiomer. In fact, in the pharmaceutical field, chirality of molecules is placed in an extremely relevant position. The administration of enantiopure drugs (i.e. a pharmaceutical that is available in one specific enantiomeric form) brings benefits in terms of improved efficacy, and reduced toxicity. These advantages forced pharmaceutical companies and health authorities to place stereochemically pure substances in a privileged position.</div>
<div style="text-align: justify;">
The large demand of enantiopure products has broken out the progress of chemical synthesis. Nowadays, the number of synthetic methods available for the preparation of chiral molecules has permitted to efficiently gain access to a myriad of enantiomerically pure compounds.</div>
Fernandohttp://www.blogger.com/profile/12522654073566755853noreply@blogger.com1tag:blogger.com,1999:blog-1819822643050307843.post-53137323338160038132014-11-15T09:00:00.000+01:002014-11-15T09:00:07.334+01:00Chiral molecules in everyday life: from natural compounds to pharmaceuticals.<div class="MsoNormal">
<span lang="EN-GB">Nature is
chiral exemplified by the fact that molecules of living organisms (both plants
and animals) such as amino acids, peptides, proteins, enzymes, carbohydrates
and nucleic acids are chiral. However, not only these biomolecules are chiral
but also many other molecules we find on a daily basis are chiral. Most of
these molecules are artificial coming from the human activity who synthesized
these compounds in order to be used as agrochemicals, or pharmaceuticals just
only to cite two relevant applications.<o:p></o:p></span><br />
<br />
<div class="separator" style="clear: both; text-align: center;">
<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhTif47qUsiBEYNhvj9LUW8cQbybLgDa-AXCAFr8YZRfzrpKXuuL7nMHYc4GePzlaZPKcFRdtKlpU6gl8vil8LheKm8VpfCzpl0Hvt1YVRQwevmSVrZn6DO05EguC42ntzeYh7QkJ_UA8U/s1600/Enantiomer-Buddies.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhTif47qUsiBEYNhvj9LUW8cQbybLgDa-AXCAFr8YZRfzrpKXuuL7nMHYc4GePzlaZPKcFRdtKlpU6gl8vil8LheKm8VpfCzpl0Hvt1YVRQwevmSVrZn6DO05EguC42ntzeYh7QkJ_UA8U/s1600/Enantiomer-Buddies.jpg" height="267" width="320" /></a></div>
<br /></div>
<div class="MsoNormal">
<span lang="EN-GB"><br /></span>
<span lang="EN-GB">Independently
of its origin (natural or artificial) these chiral molecules (namely, their
enantiomers) may have different biological activity. This can be illustrated by
means of the following examples:</span><br />
<span style="text-align: justify;"><br /></span>
<span style="text-align: justify;">The
enantiomers of limonene, both formed naturally, smell differently. One of the
enantiomers (</span><i style="text-align: justify;">S</i><span style="text-align: justify;">)-limonene smells of lemon while its mirror image compound
(</span><i style="text-align: justify;">R</i><span style="text-align: justify;">)-limonene smells of oranges. We distinguish between these two enantiomers because our nasal receptors are also made up of chiral molecules that recognise the difference.</span></div>
<div class="MsoNormal">
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<div style="text-align: justify;">
<span lang="EN-GB"><br /></span>
</div>
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<div style="text-align: justify;">
Chirality also
plays a role on odorants such as (4<i>S</i>)-(+)-carvone, which has a distinct caraway
odour, as compared to (4<i>R</i>)-(-)-carvone which has a characteristically sweet
spearmint odour. Again our nasal receptors let us to allow us to distinguish
the difference in smell.</div>
</div>
<div class="MsoNormal">
<span lang="EN-GB"><br /></span></div>
<div align="center" class="MsoNormal" style="text-align: center;">
<div class="separator" style="clear: both; text-align: center;">
<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEi81cMZqpr9jN_XwFmHOfIXY1_NYf6s1tqlSMyvLAeXMPAReURu9zu07XsytN2XZCm0HlOYM6EivVvNN1KWtgruPdA0tkO2EK6cPuMYWFSIHkS2kvsKoqYCuMQQNlTtSnp4KQS338GXnmc/s1600/fig2.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEi81cMZqpr9jN_XwFmHOfIXY1_NYf6s1tqlSMyvLAeXMPAReURu9zu07XsytN2XZCm0HlOYM6EivVvNN1KWtgruPdA0tkO2EK6cPuMYWFSIHkS2kvsKoqYCuMQQNlTtSnp4KQS338GXnmc/s1600/fig2.jpg" height="99" width="400" /></a></div>
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</v:imagedata></v:shape><span lang="EN-GB"><o:p></o:p></span></div>
<div class="MsoNormal">
<div style="text-align: justify;">
<span lang="EN-GB">These two
odorants possess different odours due to the role of chirality on bioactivity,
in this case a different 3-D fit on an odour receptor and/or on different odour
receptors. Although the role of chirality in odour perception is still a rather
modern area of interest, it should be noted that more than 285 enantiomeric
pairs (570 enantiomers) are known to exhibit either differing odours or odour
intensities.<o:p></o:p></span></div>
<div style="text-align: justify;">
<span lang="EN-GB"><br /></span></div>
</div>
<div class="MsoNormal">
<div style="text-align: justify;">
<span lang="EN-GB">Insects use
chiral chemical messengers (called pheromones) as sex attractants. Similarly to
odorants, in the case of insect pheromones chirality can influence the degree
of attractiveness of the insect. (<i>S</i>)-Olean is the female-attracting sex
pheromone of the olive fruit fly (Bactrocera oleae Gmelin). On the other hand,
the (<i>R</i>)-enantiomer attracts males of the species.<o:p></o:p></span></div>
<span lang="EN-GB"><br /></span>
<br />
<div class="separator" style="clear: both; text-align: center;">
<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjlCylrrO-1jy9QKzxz_SQvlpj7OEJtFulWbwNfK64uAkRcTVmOHUPB6gHAdlKC1ahqTZgi95GhT5p1gsqODS3tdMXNkGJd_oJ_sQHtiO4gJqNlBDW3B66W_grFv4wQ5hjxDCiqE5zsPaw/s1600/fig3.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjlCylrrO-1jy9QKzxz_SQvlpj7OEJtFulWbwNfK64uAkRcTVmOHUPB6gHAdlKC1ahqTZgi95GhT5p1gsqODS3tdMXNkGJd_oJ_sQHtiO4gJqNlBDW3B66W_grFv4wQ5hjxDCiqE5zsPaw/s1600/fig3.jpg" /></a></div>
<span lang="EN-GB"><br /></span></div>
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<div class="MsoNormal">
<div style="text-align: justify;">
<span lang="EN-GB">The same
principals are important for herbicides and pesticides containing chiral molecules.
For example, the (<i>R</i>)-(+)-enantiomer of the herbicide dichlorprop is the active
enantiomer in killing the weeds, while the (<i>S</i>)-(-)-enantiomer is inactive as an
herbicide.<o:p></o:p></span></div>
<span lang="EN-GB"><br /></span>
<br />
<div class="separator" style="clear: both; text-align: center;">
<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhJIEXDmXEbzHKAtRgYa0chgGWWiCB0jKQbXevSCNi22d1oc708gDpma7lqGdArFX6en_ePC3UfYiebNyEHtP505M_pS1MqZBiONCJnvL3hAx1VOkEdr-CcTJtWf_pbk8Z4CsJiqUg0rGA/s1600/fig4.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhJIEXDmXEbzHKAtRgYa0chgGWWiCB0jKQbXevSCNi22d1oc708gDpma7lqGdArFX6en_ePC3UfYiebNyEHtP505M_pS1MqZBiONCJnvL3hAx1VOkEdr-CcTJtWf_pbk8Z4CsJiqUg0rGA/s1600/fig4.jpg" /></a></div>
<span lang="EN-GB"><br /></span></div>
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<div class="MsoNormal">
<div style="text-align: justify;">
<span lang="EN-GB">Thus,
biology is very sensitive to chirality and the activity of pharmaceuticals
depends on which enantiomer is used. Most drugs consist of chiral molecules.
And since a drug must match the receptor in the cell, it is often only one of
the enantiomers that is of interest.<o:p></o:p></span></div>
</div>
<div class="MsoNormal">
<div style="text-align: justify;">
<span lang="EN-GB">One of the
earliest known uses of a chiral compound to cure a disease is the case of
Quinine (and other Cinchona alkaloids). These compounds possess anti-malarial
properties and were used as a medicine since the XVII century. Cinchona
extracts and quinine are also used in tonic waters, which were popularized in
the British colonies as both a malaria prophylactic and for enjoyment in the
form of a “Gin & Tonic”. Tonic water is now one of the largest industrial
uses of quinine.<o:p></o:p></span></div>
<div style="text-align: justify;">
<span lang="EN-GB"><br /></span>
</div>
<div class="separator" style="clear: both; text-align: center;">
<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjsj3K_Wu1v7dL_G_OonqOASYo_axtzRklTxNhWvg7vlSxrQsZqfG4qfydaEPPUcoBi5yBf6xGeXeV0WdSsq_4xjLOb96S-NvimnVhUYHjB9KLQf3lRm_F_9gBK2M8_Vte98VFh_8FJDWQ/s1600/fig5.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjsj3K_Wu1v7dL_G_OonqOASYo_axtzRklTxNhWvg7vlSxrQsZqfG4qfydaEPPUcoBi5yBf6xGeXeV0WdSsq_4xjLOb96S-NvimnVhUYHjB9KLQf3lRm_F_9gBK2M8_Vte98VFh_8FJDWQ/s1600/fig5.jpg" /></a></div>
<span lang="EN-GB"><br /></span>
<span lang="EN-GB"><br /></span></div>
<div align="center" class="MsoNormal" style="text-align: center;">
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<div class="MsoNormal">
<div style="text-align: justify;">
<span lang="EN-GB">Another
early use of a chiral compound to cure a disease is the case of Vitamin C
(albeit from foodstuffs). Natural Vitamin C (chemically named (+)-ascorbic
acid) has anti-scurvy activity and shows strong anti-oxidant properties.<o:p></o:p></span></div>
<span lang="EN-GB"><br /></span>
<br />
<div class="separator" style="clear: both; text-align: center;">
<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjHzaQ6ZcD4-EQ9yHmvOTa6tFNNYUtL5ZA2UBPy76mV6gi8gizEvZFWRtQE0_agShzHxvNuGkEVl0gMglSApGYdDfSVR3TUSpGrQ0OXOaW5hLRnfkMSFMRO-uujTnLSzGNUPQSw5Vyz71w/s1600/fig6.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjHzaQ6ZcD4-EQ9yHmvOTa6tFNNYUtL5ZA2UBPy76mV6gi8gizEvZFWRtQE0_agShzHxvNuGkEVl0gMglSApGYdDfSVR3TUSpGrQ0OXOaW5hLRnfkMSFMRO-uujTnLSzGNUPQSw5Vyz71w/s1600/fig6.jpg" height="121" width="320" /></a></div>
<span lang="EN-GB"><br /></span>
<br />
<div style="text-align: justify;">
<span lang="EN-GB">In certain cases,
one of the enantiomers may even be harmful. This was the case, for example,
with the drug thalidomide, which was sold in the 1960s to pregnant women. One
of the enantiomers of thalidomide helped against nausea, while the other one
could cause fetal damage.</span></div>
<br />
<br />
<div class="separator" style="clear: both; text-align: center;">
<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhrEL_qknVNSqeY5H7Jp0ZpQGTd2JhiGCz9lt7F_Ggm8ag69k2F_O-z_2CX6giv7MYXl3e8U0XoopqR9ZvXGFi67wASpPZptRIq82hESLg2azsxLz9auzVxDGp8Mes-TcRWN6elrbGSwaM/s1600/fig7.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhrEL_qknVNSqeY5H7Jp0ZpQGTd2JhiGCz9lt7F_Ggm8ag69k2F_O-z_2CX6giv7MYXl3e8U0XoopqR9ZvXGFi67wASpPZptRIq82hESLg2azsxLz9auzVxDGp8Mes-TcRWN6elrbGSwaM/s1600/fig7.jpg" height="89" width="400" /></a></div>
<br /></div>
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<br />
<div class="MsoNormal">
<div style="text-align: justify;">
<span lang="EN-GB">Since the
two enantiomers of a chiral molecule often have very different effects on
cells, it is important to be able to produce each of the two forms pure. These are
key processes in modern chemistry and is particularly important in the field of
pharmaceuticals.<o:p></o:p></span></div>
</div>
Fernandohttp://www.blogger.com/profile/12522654073566755853noreply@blogger.com5tag:blogger.com,1999:blog-1819822643050307843.post-10503667458243528432014-11-01T09:00:00.000+01:002014-11-01T16:28:55.075+01:00What is chirality? Importance in Nature.<div class="MsoNormal">
<b><u>It is all about symmetry!</u></b></div>
<div class="MsoNormal">
<span style="font-family: inherit;"><br /></span></div>
<div style="text-align: justify;">
Chirality is a property of asymmetry of objects. The word chirality is derived from the Greek word χειρ (kheir), which means "hand".</div>
<div class="MsoNormal">
<div style="text-align: justify;">
<span lang="EN-GB"><span style="font-family: inherit;">An object (or
a system) is chiral if it is not identical to its mirror image, that is, it
cannot be superposed onto it. A chiral object and its mirror image are called
enantiomorphs (Greek opposite forms) or, when referring to molecules,
enantiomers. A non-chiral object is called achiral and can be superposed on its
mirror image.<o:p></o:p></span></span><br />
<span lang="EN-GB"><span style="font-family: inherit;"><br /></span></span></div>
</div>
<div class="MsoNormal">
<div style="text-align: justify;">
<span lang="EN-GB"><span style="font-family: inherit;">Human hands
are perhaps the most universally recognized example of chirality in the real
world. The left hand is a non-superimposable mirror image of the right hand; no
matter how the two hands are oriented, it is impossible for all the major
features of both hands to coincide.</span></span></div>
</div>
<div class="MsoNormal">
<div style="text-align: justify;">
<span lang="EN-GB"><span style="font-family: inherit;">In
chemistry, chirality usually refers to molecules. A chiral molecule is a type
of molecule that has a non-superposable mirror image. Achiral molecules are
symmetrical, identical to their mirror image. These two mirror images of a
chiral molecule are called enantiomers or optical isomers. Pairs of enantiomers
are often designated as "right-" and "left-handed".<o:p></o:p></span></span></div>
</div>
<div class="MsoNormal">
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEi83jN6BtrNeXW-C-A0myUlSwVrrVSe0f5jXjt32Fd292VL9g15CrMEYJ6UPe4I0GqXjTjNtUx7H8vvYwY-HZcPVxPWHnXrD4oM5jnoa4eI10AzlVYI8y8_qfkj8rjq2vrc28mgs_l8HCU/s1600/chirality.png" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEi83jN6BtrNeXW-C-A0myUlSwVrrVSe0f5jXjt32Fd292VL9g15CrMEYJ6UPe4I0GqXjTjNtUx7H8vvYwY-HZcPVxPWHnXrD4oM5jnoa4eI10AzlVYI8y8_qfkj8rjq2vrc28mgs_l8HCU/s1600/chirality.png" height="217" width="320" /></a></div>
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<span lang="EN-GB"><span style="font-family: inherit;"><b><u>Nature is
chiral</u></b><o:p></o:p></span></span></div>
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<span style="font-family: inherit; text-align: justify;">One may
well think that both forms of chiral molecules ought to be equally common in
nature. But when we study the molecules of the cells in close-up, it is evident
that nature mainly uses one of the two enantiomers. That is why we have – and
this applies to all living material, both vegetable and animal – amino acids,
and therefore peptides, enzymes and other proteins, only of one of the mirror
image forms. Carbohydrates and nucleic acids like DNA and RNA are other
examples.</span></div>
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Thus the enzymes in our cells are chiral, as are other receptors that play an important part in cell machinery. This means that they prefer to bind to one of the enantiomers. In other words, the receptors are extremely selective; only one of the enantiomers fits the receptor's site like a key that fits a lock.</div>
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Since the two enantiomers of a chiral molecule often have totally different effects on cells, it is important to be able to produce each of the two forms pure. Chemistry brings us solutions to achieve this goal.</div>
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For more info, see also an interesting video "What is chirality and how did it get in my molecules?" at <a href="http://ed.ted.com/lessons/michael-evans-what-is-chirality-and-how-did-it-get-in-my-molecules">http://ed.ted.com/lessons/michael-evans-what-is-chirality-and-how-did-it-get-in-my-molecules</a></div>
Fernandohttp://www.blogger.com/profile/12522654073566755853noreply@blogger.com2tag:blogger.com,1999:blog-1819822643050307843.post-23568882298306090862014-10-31T09:00:00.000+01:002014-10-31T16:13:33.922+01:00Presentation of the REMOTEcat blog.<div class="MsoNormal" style="mso-layout-grid-align: none; mso-pagination: none; text-align: justify; text-autospace: none;">
<span lang="EN-GB">REMOTEcat is the acronym for the project entitled
"Asymmetric organocatalysts for remote functionalization strategies" funded
by the People Programme (Marie Curie Actions) of the EU. Currently, I am
carrying out this project at the <a href="http://chem.au.dk/en/research/research-areas/organicchemistry/catalysis/" target="_blank">Center for Catalysis</a> (<a href="http://chem.au.dk/en/" target="_blank">Department of Chemistry</a>, <a href="http://www.au.dk/en/" target="_blank">Aarhus University</a>,
Denmark) under the supervision of </span><span lang="EN-GB">Prof. Karl Anker </span><span lang="EN-GB">Jørgensen</span><span lang="EN-GB">.</span><br />
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In line with <a href="http://ec.europa.eu/programmes/horizon2020/en/h2020-section/responsible-research-innovation" target="_blank">EU research & innovation policy</a>, REMOTEcat assumes
that responsible research implies an effort to the scientific promotion of
science encouraging public participation and understanding of science. The goal
is to create awareness among the public about the research work performed in
the Marie Curie Action and their implications in society.<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjgB6cZEYmjMtk_PVMML2gAE_6Dc22n5T3j9_o1lxUcShBGgrpcMHVMV-KWBZ-1obmlryOgxH0IkgbPnG0gES9AJSYKOGuJ-C3J3yas1DNJCkRoqLI7vgyb89QpL6KvYxGe7m7RXhx4uEw/s1600/WORDLE_RRI+cloud_0.png" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjgB6cZEYmjMtk_PVMML2gAE_6Dc22n5T3j9_o1lxUcShBGgrpcMHVMV-KWBZ-1obmlryOgxH0IkgbPnG0gES9AJSYKOGuJ-C3J3yas1DNJCkRoqLI7vgyb89QpL6KvYxGe7m7RXhx4uEw/s1600/WORDLE_RRI+cloud_0.png" height="136" width="200" /></a></div>
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<b><u>About the project</u></b><br />
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<span style="text-align: justify;">REMOTEcat is a chemistry project. In particular,
organic chemistry, and in more detail, asymmetric organocatalysis.</span></div>
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Many chemical processes would not occur (at least, not at a rate that has any practical application) without catalysts. Catalysts (i.e. a substance that modifies the rate of a chemical reaction) have thus become indispensable in a wide range of industrial reactions. But the study of these systems can offer much more: it can change our understanding of fundamental chemical concepts and challenge us to rethink the “rules” of the chemical world.</div>
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In general, enantioselective catalysis (usually known as asymmetric catalysis) mostly refers to the use of chiral metal catalysts. It is very commonly encountered, as it is effective for a broader range of transformations than any other synthetic methods. Small organic molecules without metals can also exhibit catalytic properties, In the early 2000s, these organocatalysts were considered "new generation" and are competitive to traditional metal-containing catalysts.</div>
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Research in the area of organocatalysis moves at breathtaking speed: many catalytic reactions now considered to be “standard issue” by organic chemists were almost unthinkable just 10 years ago. The ability to synthesize and selectively modify small organic molecules is crucial for many applications, including drug discovery and the search for new materials. The development of new organocatalysts often makes it possible to generate previously unattainable compounds, which could have unique physical, chemical or biological properties.</div>
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<u style="text-align: justify;"><b>Why am I launching this blog?</b></u></div>
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Probably, there are too many weird words in just only a few lines above. However, do not be concerned
about this. The idea of launching this blog is to build bridges between the
research I am doing and non-specialists. It is science for non-scientists.</div>
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<span lang="EN-GB">What I would like to do is
to introduce the basic concepts of organic chemistry involved in the project through
case examples and situations of our daily lives. Gradually, and later on, going
into more details about the research carried out in the project </span><span lang="EN-GB">in the most entertaining manner possible
and understandable to everyone.<o:p></o:p></span></div>
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Hope you find interesting and understandable the contents of the blog. Any comments or suggestions for their improvement are welcome.<br />
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<b><u>About me</u></b><br />
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LinkedIn: <a href="http://dk.linkedin.com/pub/fernando-tur/2a/1a8/535/">dk.linkedin.com/pub/fernando-tur/2a/1a8/535/</a></div>
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ResearchGate: <a href="https://www.researchgate.net/profile/Fernando_Tur">https://www.researchgate.net/profile/Fernando_Tur</a></div>
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Twitter: @fernando_tur</div>
Fernandohttp://www.blogger.com/profile/12522654073566755853noreply@blogger.com0