氨普霉素C8'-差向异构胸腺嘧啶吡喃糖基氨基酸核心的合成。

Synthesis of the C8'-epimeric thymine pyranosyl amino acid core of amipurimycin.

作者信息

Markad Pramod R, Kumbhar Navanath, Dhavale Dilip D

机构信息

Garware Research Centre, Department of Chemistry, Savitribai Phule Pune University (Formerly University of Pune), Pune-411007, India.

出版信息

Beilstein J Org Chem. 2016 Aug 5;12:1765-71. doi: 10.3762/bjoc.12.165. eCollection 2016.

DOI:10.3762/bjoc.12.165

PMID:27559421

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4979907/

Abstract

The C8'-epimeric pyranosyl amino acid core 2 of amipurimycin was synthesized from D-glucose derived alcohol 3 in 13 steps and 14% overall yield. Thus, the Sharpless asymmetric epoxidation of allyl alcohol 7 followed by trimethyl borate mediated regio-selective oxirane ring opening with azide, afforded azido diol 10. The acid-catalyzed 1,2-acetonide ring opening in 10 concomitantly led to the formation of the pyranose ring skeleton to give 2,7-dioxabicyclo[3.2.1]octane 12. Functional group manipulation in 12 gave 21 that on stereoselective β-glycosylation afforded the pyranosyl thymine nucleoside 2 - a core of amipurimycin.

摘要

氨普米星的C8'-差向异构吡喃糖基氨基酸核心2由D-葡萄糖衍生的醇3经13步反应合成，总收率为14%。因此，烯丙醇7经夏普莱斯不对称环氧化反应，随后硼酸三甲酯介导的环氧乙烷环与叠氮化物的区域选择性开环反应，得到叠氮二醇10。10中的酸催化1,2-丙酮叉环开环反应同时导致吡喃糖环骨架的形成，得到2,7-二氧杂双环[3.2.1]辛烷12。对12进行官能团操作得到21，21经立体选择性β-糖基化反应得到吡喃糖基胸腺嘧啶核苷2——氨普米星的一个核心。