Academician Zhou Qilin of Nankai University and Professor Zhu shoufei's research team: Based on iridium catalyzed asymmetric hydrogenation of α - substituted acrylic acid to synthesize polydeoxypropionate structure

The lead polydeoxypropionate has a continuous 1,3-methylene spacer chiral methyl structure, which widely exists in the natural products of polyketones The natural products with polydeoxypropionate structure often have strong biological activities such as anticancer, antibacterial, cell inhibition, insect hormone activity and so on Therefore, the synthesis of this kind of structure has been the focus of chemists Iterative synthesis, that is, after a series of reaction cycles, the same functional group is repeatedly constructed to introduce multiple repeated chiral centers, which is widely used in the synthesis of natural products of polyketones At present, most of the developed asymmetric iterative methods rely on the induction of chiral cofactors or reagents, and there are only a few examples of asymmetric catalysis Recently, academician Zhou Qilin of Nankai University and Professor Zhu shoufei's research team developed a new strategy for the synthesis of polydeoxypropionate with high yield, high stereoselectivity, simple operation and even no column chromatography based on the asymmetric catalytic hydrogenation of α - substituted Acrylate Catalyzed by iridium In this method, the amount of catalyst can be reduced to 1 / 10000 at least, and sensitive metal reagent is not needed Phthioceranic acid, a natural product, and the key intermediates of ionomycin and borrelidin (DOI: 10.1021 / ACS Orglett 8b01193) were synthesized with the highest yield Prof Zhou Qilin, organic chemist, Professor of Nankai University, academician of Chinese Academy of Sciences He graduated from the Department of chemistry, Lanzhou University in 1982, and was admitted to Shanghai Institute of organic chemistry, Chinese Academy of Sciences in the same year In 1987, he received a doctor's degree From 1988 to 1996, he worked as a postdoctoral student in East China University of science and technology, Max Planck Institute in Germany, Basel University in Switzerland and Trinity University in the United States From 1996 to 1999, he served as associate professor, professor and doctoral supervisor of East China University of science and technology In 1997, he was supported by the national fund for Distinguished Young Scholars In 1999, he was employed as a distinguished professor in the "Yangtze River scholars Award Program" of the Ministry of education and a professor in the school of chemistry of Nankai University He was elected academician of the Chinese Academy of Sciences in 2009 In 2010, he was elected vice president of China Chemical Association In 2013, he was elected to the Royal Society of chemistry Professor Zhou Qilin is mainly engaged in organometallic chemistry, organic synthesis methodology, asymmetric catalysis, bioactive compounds and chiral drug synthesis He developed a new class of chiral spiro catalysts This kind of catalyst has shown excellent catalytic efficiency and enantioselectivity in many asymmetric synthesis reactions It is called "Zhou's catalyst" by domestic and foreign counterparts, which has an important influence in the world and has been successfully used in the production of a variety of chiral drugs He has published more than 240 research papers, 14 books (chapters) and 13 invention patents In 2005, he won the "organic synthesis Creation Award" of Organic Chemistry Committee of China Chemical Society, in 2006, he won the "Huang yaozeng Metal Organic Chemistry Award" of China Chemical Society, in 2007 and 2013, he won the "first prize of natural science" of Tianjin, in 2007, he won the "lecture award of Japan academic revitalization society", in 2010, he won the "contribution award of Chinese overseas Chinese community (innovative talents)", in 2012, he won the "chirality" of China Chemical Society Academic Award ", won the" chemical Contribution Award "of China Chemical Society in 2018 It was rated as "Tianjin model worker", "Tianjin excellent science and technology worker" and "national excellent science and technology worker" At present, he is the editor in chief of the Journal of chemistry, deputy editor in chief of ccscs, organic chemistry, acc.chem Res., angelw.chem Int ed., chem SCI., J org Chem., adv synth Catalyst., J mol.catalyst Chem., asianj Org Chem, tetrahedron, tetrahedron lett, Helvetica Acta, topical Editorial Committee and consultant Editorial Committee of journals and series such as organotallic chemistry Prof Zhu shoufei profile Prof Zhu shoufei, Professor of Nankai University, doctoral supervisor, winner of national fund for Distinguished Young Scholars, and leader of national "ten thousand talents plan" In 2000 and 2005, he obtained bachelor's degree and doctor's degree from school of chemistry, Nankai University; in 2012 ‒ 2013, he worked as a postdoctoral student in Tokyo University, Japan; since 2005, he has worked in the Institute of elemental organic chemistry, School of chemistry, Nankai University Professor Zhu shoufei is mainly engaged in the research of catalytic organic synthesis chemistry, focusing on several kinds of important organic synthesis reactions with hydrogen transfer as the key step The main achievements are as follows: 1) the concept of "chiral proton shuttle" is proposed, which provides a new solution for asymmetric proton transfer reaction catalyzed by metal It is called "promising future research field", and it is for domestic and foreign It was adopted by many research groups and triggered a series of related theoretical studies 2) It has been found that the insertion reaction of catalytic carbene to B-H bond and its asymmetric transformation have been realized, which is considered as "an attractive method for the synthesis of chiral organic boron block", and has been followed up by many research groups 3) A variety of efficient catalysts for olefin hydrogenation and hydrosilylation have been developed, and a variety of important carboxylic acid non steroidal anti-inflammatory drugs and alkaloids have been synthesized efficiently Some of the achievements have been adopted by pharmaceutical companies He published 90 papers, wrote 2 chapters and chapters, and was authorized 5 Chinese patents and applied for 3 international patents He has been selected into the "new century excellent talents support plan" (2010) of the Ministry of education, the "Excellent Youth Science Fund" (2012) of the National Foundation Committee, the "ten thousand talents plan" (2013), the "131" innovative talents training project of Tianjin (Level 1, 2015), the "young and middle-aged leading talents in science and technology innovation" (2015), the "Yangtze River scholars" of the Ministry of science and technology Talent plans and projects such as "Young Scholars (2016)," National Outstanding Youth Fund "(2016)," ten thousand talents plan "(2017) He has won 2 first prizes of Tianjin Natural Science (2007 and 2013, the third adult), youth Chemistry Award of China Chemical Society (2012), Tianjin Youth Science and Technology Award (2014), Asia core programming Awards (2015), Tianjin Youth May 4th Medal (2016) and other awards Leading scientific research achievements: Based on the asymmetric hydrogenation of α - substituted acrylic acid catalyzed by iridium to synthesize polydeoxypropionate, the author found that iridium catalyst modified by phosphine nitrogen ligands with large steric hindrance on phosphine can effectively catalyze α - substituted acrylic acid, obtaining 100% conversion rate and 97% ee value Triethylamine can accelerate the hydrogenation obviously, the reaction can be enlarged to 5g scale, and the amount of catalyst can be reduced to 1 / 10000 Figure 1 Condition optimization of asymmetric hydrogenation (source: organicletters) Then, the author condensed and reduced the hydrogenated product with michaelitic acid, and then introduced α - substituted acrylic acid structure after Mannich like reaction and hydrolysis for hydrogenation Excellent EE and Dr values can be obtained for R or S-type catalysts, which fully shows that the second chiral methyl configuration is completely controlled by the catalyst The yield of the whole iterative process is more than 83%, and the intermediate process does not need column chromatography, because impurities can be removed in the post-processing step of hydrolysis Fig 2 After the introduction of the second chiral methyl group (source: Organic letters) in the first iteration, the author synthesized the ternary deoxypropionate structure widely existing in the natural product structure by using this strategy The target product can also be obtained with high yield and good stereoselectivity Fig 3 In the second iteration, the third chiral methyl (source: Organic letters) was introduced In order to demonstrate the effectiveness of this iterative synthesis process, the author synthesized the key intermediates of the natural products ionomycin and borrelidin The yield and optical purity of the intermediates were effectively improved compared with the synthesis methods in the literature Figure 4 Synthesis of key intermediates of ionomycin and borrelidin (source: Organic letters) Finally, the author synthesized phthioceranic acid, a side chain of lipid structure on the cell wall of Mycobacterium tuberculosis This structure plays an important role in the study of immune response of Mycobacterium tuberculosis infection Therefore, the efficient synthesis of this structure may accelerate the effective development of Mycobacterium tuberculosis vaccine Finally, phthioceranic acid was synthesized in 19 steps and 34% overall yield This is the highest yield reported in the literature Figure 5 Total synthesis of phthioceranic acid (source: organicletters) The research results are published in organic letters (DOI: 10.1021/acs.orglett.8b01193) The first author of this paper is Che Wen, a doctoral student of academician Zhou Qilin of Nankai University The corresponding authors are Professor Zhou Qilin and Professor Zhu shoufei This work has been supported by NSFC, the "111 plan" of the Ministry of education and the "ten thousand people plan" of the state Nowadays, people and scientific research have been paid more and more attention in the economic life China has ushered in the "node of science and technology explosion" Behind the progress of science and technology is the work of countless scientists In the field of chemistry, in the context of the pursuit of innovation driven, international cooperation has been strengthened, the influence of Returned Scholars in the field of R & D has become increasingly prominent, and many excellent research groups have emerged in China For this reason, CBG information adopts the 1 + X reporting mechanism CBG information, chembeango app, chembeango official microblog, CBG wechat subscription number and other platforms jointly launch the column of "people and scientific research", approach the domestic representative research group, pay attention to their research, listen to their stories, record their 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