Zhai Hongbin & Cheng bin, School of chemistry and chemical engineering, Lanzhou University

Indole alkaloids are a kind of natural organic small molecules with indole structure isolated from litmus plants of Oleaceae Many of them have become star molecules because of their unique structure and important biological activity and are favored by many synthetic chemists Recently, Zhai Hongbin and Cheng bin research team of School of chemistry and chemical engineering of Lanzhou University published an article titled "collective totalsynthesis of (−) - lundurines a − C" in org Lett., a famous journal of organic chemistry, and reported their important progress in the study of total synthesis of these alkaloids (doi: 10.1021 / ACS Orglett 8b00210) Brief introduction of Zhai Hongbin & Cheng bin scientific research team: at present, the scientific research team takes the integration of natural products with important biological activities as the core, devotes to developing novel organic synthesis methods and strategies, and pursues the simple, efficient and cluster synthesis of target compounds At the same time, the team also carried out heterocyclic and pharmaceutical chemistry research The research group has been recruiting postdoctors and research assistants for a long time We warmly welcome students who have enthusiasm for research and are looking forward to making significant achievements in related fields to join in the exploration of organic chemistry Brief introduction to Professor Zhai Hongbin, Professor, doctoral supervisor and project leader of School of chemical biology and biotechnology, Shenzhen Graduate School, Peking University In 1985, he graduated from Peking University; in 1988, he graduated from Peking Union Medical College (former China Union Medical University) / Chinese Academy of Medical Sciences; in 1995, he received his pH Researcher of Shanghai Institute of organic chemistry, Professor of Lanzhou University from 2010 to 2015, director of State Key Laboratory of functional organic molecular chemistry, and professor of Shenzhen Graduate School of Peking University (Nanguo Yanyuan) since 2015 In 1999, he was supported by the Hundred Talents Program of the Chinese Academy of Sciences, in 2006, by the National Science Fund for Distinguished Young Scholars, in 2009, he was selected as the national candidate for the new century million talents project, in 2012, he enjoyed the special allowance of the State Council, in 2015, he was selected as the national leader of Shenzhen, in 2016, he was selected as the innovation talent promotion plan of the Ministry of science and technology, and in 2017, he was selected as the science and technology innovation leader of the 10000 Talents Program of the Ministry of science and technology The research fields are total synthesis of natural products and organic synthesis methodology Brief introduction to associate professor Cheng bin, associate professor, School of chemistry and chemical engineering, Lanzhou University He graduated from Huaibei Normal University in 2000, studied in Shanghai Institute of organic chemistry, University of science and technology of China (co training, tutor: Professor Zhai Hongbin) from 2004 to 2009, and obtained a doctor of Science degree From September 2009 to April 2012, he worked as an assistant researcher in Shanghai Institute of organic chemistry From October 2014 to October 2015, I worked as a visiting scholar at the University of Utah (Tutor: Matthew S sigma) Since May 2012, he has worked in the school of chemistry and chemical engineering of Lanzhou University and the State Key Laboratory of functional organic molecular chemistry Cutting edge scientific research achievements: (−) - cluster high-efficiency total synthesis of lundurines a-c kopsia tenuis, which grows in Malay Peninsula, has been used as folk medicine and is an important source of many biologically active alkaloids In the past century, hundreds of alkaloids with complex structures have been isolated and identified, many of them have very important biological activities Therefore, more and more synthetic chemists at home and abroad pay attention to this kind of organic natural products (−) - lundurines A-D is the most unique four indole alkaloids (Fig 1) They all contain a five substituted cyclopropane and dihydroindole structure, and almost all the chiral centers in the whole molecule are concentrated on this cyclopropane It is worth noting that such a special structure is unique among all natural products It was found that (- lundurines B and D were toxic to B16 melanoma cells and could reverse the resistance of vincristine resistant KB cells Fig 1 Recently, Zhai Hongbin and Cheng bin of the school of chemistry and chemical engineering of Lanzhou University reported the cluster high-efficiency total synthesis of (- - lundurinesa – C They used optically pure l-pyroglutamate as the chiral source to construct the first chiral quaternary carbon, and induced the construction of three other chiral centers The pyrrolidone ring was constructed by tandem reduction amination / internal amidation, and the connection between the left chromol segment and the right amino acid ester segment was realized Then, the intermediate eight membered ring was constructed by the intramolecular C-H alkylation of indole 2 Catalyzed by palladium After completing the construction of 6 / 5 / 8 / 5 tetracycline framework, they constructed the core penta substituted cyclopropane structure by using sulfonylhydrazone to generate intramolecular form of [3 + 2] cycloaddition / removal of one molecule nitrogen under the promotion of Lewis acid Finally, the oxidation state of pyrrolidone ring was adjusted according to the needs of the author After 15-16 steps, the total synthesis of (−) - lunduriesa – C was realized The whole synthesis step was simple and efficient Using the cheap optically pure chiral source L-pyroglutamic acid as the starting compound (Fig 2), the author synthesized aldehyde19 by the route reported in the literature, and then the stork − Zhao − Wittig olefinization reaction took place to obtain alkenyliodine 18 with high Z / E ratio In the same condition, the latter can be converted into amine 20, thus realizing the reuse of lactam 21 On the other hand, after n-methoxycarbonylation and desilication of 5-methoxychromol TBS ether, chromol 22 was obtained, IBX was oxidized to corresponding aldehyde, and the intramolecular c-h-linked alkenylation precursor 16 was obtained by reductive amination / internal amidation reaction with amine 20 Fig 2 Synthesis of C-H alkenylation precursor 16 (source: org Lett.) after obtaining 16, the author screened a series of reaction conditions (Table 1), including reaction temperature and palladium divalent catalyst Finally, it was found that the tetracyclic compound 15 could be obtained with the highest yield of 58% under the conditions of PD (TFA) 2, acok and 90oC Table 1 Optimization of intramolecular C-H bond alkenylation conditions (source: org Lett.) after that, the author started functional group transformation on the side chain of ester group After reduction of ester group by NaBH4, double construction of hydrogenation reduction, Albright Goldman oxidation and two-step homology operation, aldehyde 25 was obtained After condensation with sulfonylhydrazine, cyclopropane precursor 14 was obtained According to the work of echavarren group (J am Chem SOC 2016, 138, 3671 − 3674), sulfonylhydrazone 14 was formed by intramolecular [3 + 2] cycloaddition to pyrazoline intermediate 26 under the promotion of ET 2 O ＜ BF 3 Lewis acid The compound is very unstable and will immediately remove one molecule of nitrogen to obtain cyclopropane product 27 Finally, the oxidation state of pyrrolidone ring was adjusted The α - position deprotonation of (−) - lunduric C was obtained by the direct reduction of lactam with me 2S · BH 3, and then (−) - lundurine a was obtained by the oxidation of 27 with Mukaiyama oxidant Finally, the synthesis of (−) - lundureb was completed by O-methylation of unsaturated lactam and reduction of NaBH 4 Figure 3 (source: org Lett.) the research work was recently published in org Lett (org Lett., 2018, 20, 1509 – 1512), mainly completed by Xu Wei, a doctoral student 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 demeanor, and explore their scientific research spirit.