Guo Haiming, Professor of Henan Normal University: synthesis of polycyclic fused anisodane by asymmetric dearylation cycloaddition of 2-nitrobenzofuran

The introduction of anisodane skeleton (8-azabicyclo [3.2.1] octane) is widely found in many natural products and drug molecules These compounds play a key role in the clinical treatment of immune, neurological and psychiatric diseases In particular, most of the natural products and drug active molecules are in the form of polycyclic fused anisodane skeleton (Fig 1) The asymmetric synthesis of anisodamine compounds with simple structure is mostly realized by multi-step reaction from chiral raw materials It is a challenging work to construct the complex anisodane skeleton directly by catalytic asymmetric method Recently, Professor Guo Haiming's research group of Henan Normal University constructed a kind of polycyclic fused anisodanes by catalytic asymmetric dearomatization The results were published online in org Lett (DOI: 10.1021/acs.orglett.9b04108) Fig 1 Important drug molecules and natural products containing polycyclic fused anisodane skeleton (source: org Lett.) brief introduction of Professor Guo Haiming's research group Professor Guo Haiming's research group has been committed to the selective structural modification of nucleoside compounds The research group has developed the synthesis methodology of nucleoside selective structural modification by combining the new methods, new reactions, new reagents and new methods in chemical synthesis, and has made outstanding achievements in the selective modification of purine compounds at C6, C8, N9 and pyrimidine at n-1 He edited a monograph "chemical modification of nucleoside bases", which was published by Science Press and supported by the national science and technology academic works publishing fund In the structural modification of purine compounds, it was found that the N7 = C8 position of purine ring can react with D-A cyclopropane to form a de aromatization ring addition reaction After that, a series of catalytic asymmetric de aromatization reactions of purine and benzoxazole compounds were developed in cooperation with youshuli (angel Chem Int ed., 2016, 55, 14111; Chem, 2019, 5, 156; org Chem Front, In 2019, 6, 863, etc.), breakthroughs have also been made in the construction of chiral tricyclic purines and tricyclic benzoxazoles Guo Haiming, professor and doctoral supervisor of Henan Normal University, deputy director of Henan Key Laboratory of organic functional molecules and drug innovation, and executive director of Henan Pharmaceutical Association Since independent work, he has published more than 80 papers in SCI journals as the first or corresponding author It has 15 authorized invention patents, 1 second prize of national science and technology progress and 2 first prize of science and technology progress of Henan Province as the main finisher In 2017, he was selected as the leading talent of the national ten thousand talents plan; in 2016, he was selected as the national young and middle-aged leading talent of scientific and technological innovation; in 2016, he was selected as the expert enjoying the special allowance of the State Council; in 2015, he was selected as the National candidate of the one million talents project, and was awarded as the national outstanding contribution young and middle-aged expert; in 2009, he was selected as the winner of the new century excellent talents support plan of the Ministry of education Leading scientific research achievements: the synthesis of polycyclic fused anisodane compound by asymmetric dearomatization cycloaddition of 2-nitrobenzofuran is the structural parent nucleus of many natural products and drug active molecules Asymmetric synthesis of anisodamine compounds with simple structure is usually carried out by multi-step reaction with chiral compounds as raw materials It is a challenging work to construct the complex anisodane skeleton directly by catalytic asymmetric method On the basis of the previous study on the asymmetric dearylation of heteroaromatic compounds such as purine, the research group tried to use the asymmetric [3 + 2] cycloaddition dearylation of 2-nitrobenzofuran and imine ylide to synthesize polycyclic fused anisodane compounds (Fig 2) The results show that in the presence of the Chiral Biphenyl diphosphonate ligand L9, the bivalent copper catalyst has better catalytic activity than the common monovalent copper catalyst, and the target product can be obtained with high yield and high stereoselectivity at a low catalyst dosage of 1% The template reaction can be enlarged to gram scale, and the amount of catalyst can be reduced to 5 / 1000 Fig 2 Asymmetric de aromatization of 2-nitrobenzofuran and ylide (source: org Lett.) in order to investigate the substrate application scope of the synthesis method, the author investigated a series of imine substrates with different groups (Fig 3) Firstly, the electronic effect of indole aromatic ring and the different substituents of ester group and alkyl group of carboline were investigated These substrates can react smoothly After that, the author investigated the different positions of nitrobenzofuran, and found that both electron donor and electron acceptor groups had good compatibility Subsequently, the practicability of the reaction was studied (Fig 4) It is found that the functional groups of the products can be transformed well, and the EE values of the derivatives can be maintained Figure 3 Study on the application scope of substrate (source: org Lett.) Figure 4 Gram level reaction and functional group transformation (source: org Lett.) to sum up, the author first reported A series of polycyclic fused anisodane compounds were synthesized by asymmetric dearylation cycloaddition of 2-nitrobenzofuran and ylide The product has excellent yield and stereoselectivity This achievement was recently published in org Lett The authors of this paper are: Zhen Wang, Dong Chao Wang, * Ming Sheng Xie, GUI Rong Qu, and Hai Ming Guo * 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 website, chembeangoapp, chembeango official micro blog, CBG information wechat subscription number and other platforms jointly launch the column of "people and scientific research", approach the representative research groups in China, pay attention to their research, listen to their stories, record their demeanor, and explore their scientific research spirit.