2'-C-β-甲基鸟苷的高效合成

Efficient synthesis of 2'-C-beta-methylguanosine.

作者信息

Li Nan-Sheng, Piccirilli Joseph A

机构信息

Howard Hughes Medical Institute, Department of Biochemistry & Molecular Biology, University of Chicago, Chicago, Illinois 60637, USA.

出版信息

J Org Chem. 2006 May 12;71(10):4018-20. doi: 10.1021/jo0602165.

DOI:10.1021/jo0602165

PMID:16674089

Abstract

2'-beta-Methyl nucleosides have potential value as therapeutic agents and as nucleoside analogues for exploring RNA biology. Here we develop a strategy for efficient synthesis for 2'-C-beta-methylguanosine (3). Starting from 1,2,3,5-tetra-O-benzoyl-2-C-beta-methyl-d-ribofuranose (1) and N2-acetylguanine, we obtained the title compound in two steps (78% overall yield) with high stereoselectivity (beta/alpha > 99:1) and high regioselectivity (N9/N7 > 99:1). Extension of this strategy to the classic synthesis of guanosine also resulted in high stereoselectivity (beta/alpha = 99:1) and improved regioselectivity (N9/N7 = 97:3).

摘要

2'-β-甲基核苷作为治疗剂和用于探索RNA生物学的核苷类似物具有潜在价值。在此，我们开发了一种高效合成2'-C-β-甲基鸟苷（3）的策略。从1,2,3,5-四-O-苯甲酰基-2-C-β-甲基-D-核糖呋喃糖（1）和N2-乙酰鸟嘌呤开始，我们通过两步反应得到了目标化合物（总收率78%），具有高立体选择性（β/α>99:1）和高区域选择性（N9/N7>99:1）。将该策略扩展到鸟苷的经典合成中，也得到了高立体选择性（β/α=99:1）和改进的区域选择性（N9/N7=97:3）。