通过9-(2-甲苯磺酰基乙烯基)-9H-嘌呤的不对称[3+2]环加成反应合成氮杂环核苷类似物

Synthesis of Azacyclic Nucleoside Analogues via Asymmetric [3 + 2] Cycloaddition of 9-(2-Tosylvinyl)-9H-purines.

作者信息

Zhang Dan-Jie, Xie Ming-Sheng, Qu Gui-Rong, Gao Yao-Wei, Guo Hai-Ming

机构信息

Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, School of Chemistry and Chemical Engineering, Henan Normal University , Xinxiang, Henan 453007, P. R. China.

出版信息

Org Lett. 2016 Feb 19;18(4):820-3. doi: 10.1021/acs.orglett.6b00108. Epub 2016 Feb 4.

DOI:10.1021/acs.orglett.6b00108

PMID:26844591

Abstract

With 9-(2-tosylvinyl)-9H-purines as the dipolarophiles, a series of chiral azacyclic nucleosides with four continuous stereocenters were obtained in 86-99% yields, >20:1 dr, and 94 → 99% ee via the Cu(I)-catalyzed asymmetric [3 + 2] cycloaddition. Both (E)- and (Z)-9-(2-tosylvinyl)-9H-purines were suitable dipolarophiles, enriching the structure diversity of azacyclic nucleosides. Furthermore, when α-methyl imino ester was explored, the corresponding azacyclic nucleoside with a chiral quaternary stereocenter could also be afforded with excellent results.

摘要

以9-(2-甲苯磺酰基乙烯基)-9H-嘌呤作为亲偶极体，通过铜(I)催化的不对称[3 + 2]环加成反应，以86 - 99%的产率、>20:1的非对映体比例和94→99%的对映体过量得到了一系列具有四个连续立体中心的手性氮杂环核苷。(E)-和(Z)-9-(2-甲苯磺酰基乙烯基)-9H-嘌呤都是合适的亲偶极体，丰富了氮杂环核苷的结构多样性。此外，当探索α-甲基亚氨基酯时，也能以优异的结果得到具有手性季碳立体中心的相应氮杂环核苷。