文献类型：期刊文献

英文题名：Diversified ring expansion of saturated cyclic amines enabled by azlactone insertion

作者：Wu, Licheng[1,2];Xia, Hanyu[1,2];Bai, Jiahao[1,2];Xi, Yang[1,2];Wu, Xianqing[1,2];Gao, Li[1,2];Qu, Jingping[1,2];Chen, Yifeng[1,2,3,4]

机构：[1]East China Univ Sci & Technol, Feringa Nobel Prize Scientist Joint Res Ctr, Frontiers Sci Ctr Materiobiol & Dynam Chem, Sch Chem & Mol Engn,Key Lab Adv Mat, Shanghai, Peoples R China;[2]East China Univ Sci & Technol, Feringa Nobel Prize Scientist Joint Res Ctr, Frontiers Sci Ctr Materiobiol & Dynam Chem, Sch Chem & Mol Engn,Joint Int Res Lab Precis Chem, Shanghai, Peoples R China;[3]Chinese Acad Sci, Shanghai Inst Organ Chem, State Key Lab Organometall Chem, Shanghai, Peoples R China;[4]Henan Normal Univ, Sch Chem & Chem Engn, Xinxiang, Peoples R China

年份：2024

卷号：16

期号：12

外文期刊名：NATURE CHEMISTRY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001360213900001)，CCR-EXPANDED(收录号:WOS:001360213900001)】；

基金：We thank the Analysis and Testing Center of East China University of Science and Technology for help with NMR and HRMS analysis. Y.C. thanks B. Feringa (University of Groningen) for insightful discussion. This work was supported by the National Natural Science Foundation of China (22171079, 22371071, 92356301 and T2488302), Sinopec Seeding Program (C0607-0876), Natural Science Foundation of Shanghai (21ZR1480400), Shanghai Municipal Science and Technology Major Project (grant no. 2018SHZDZX03), the Program of Introducing Talents of Discipline to Universities (B16017), the China Postdoctoral Science Foundation (2023TQ0118), Shanghai Sailing Program (23YF1408800) and the Fundamental Research Funds for the Central Universities.

语种：英文

摘要：Saturated N-heterocycles are ubiquitous structures among natural products and biologically active compounds. Therefore, the development of synthetic methods for the construction of N-heterocycles is of great importance in the synthetic community. Altering the ring system of these motifs to analogues with different ring sizes by employing molecular editing techniques would be highly appealing in medicinal chemistry. We present herein the direct insertion of glycine derivatives as two-carbon synthons into unstrained five- or six-membered saturated cyclic amines at predictable sites, enabling the construction of synthetically challenging medium-sized azacycles through sequential Ru-catalysed C-C bond formation, retro-aza-Michael addition and a lactamization process. Upon further derivation, we leverage this homologation platform to realize modular insertion of one- or two-carbon units into the aliphatic rings. The conversion of a single azacycle into up to five others provides a promising toolbox for diversifying existing drug candidates and increasing the prospects for clinical success. Saturated N-heterocycles are ubiquitous structures among natural products and biologically active compounds, but methods to edit the ring size of these substructures are scarce. Now the ring expansion of unactivated cyclic amines has been achieved via sequential Ru-catalysed C-C bond formation, retro-aza-Michael addition and a lactamization process to construct synthetically challenging medium-sized azacycles.