2'-C-β-氟甲基尿苷的合成。

Synthesis of 2'-C-beta-fluoromethyluridine.

作者信息

Dai Qing, Piccirilli Joseph A

机构信息

Howard Hughes Medical Institute, Department of Biochemistry & Molecular Biology, The University of Chicago, 5841 S. Maryland Ave., MC 1028, Chicago, Illinois 60637, USA.

出版信息

Org Lett. 2003 Mar 20;5(6):807-10. doi: 10.1021/ol027364b.

DOI:10.1021/ol027364b

PMID:12633077

Abstract

[reaction: see text] 2'-C-beta-Fluoromethyluridine (17) represents both a potentially important biological agent and a tool for biochemical analysis. Here we describe the first synthesis of this compound starting from uridine. The key steps include protection of the uracil base with methoxyethoxymethyl (MEM) chloride, conversion to the corresponding 2'-C-alpha-epoxide, and regioselective opening of the oxirane ring with potassium fluoride/hydrogen fluoride. Subsequent acetylation of the 3'- and 5'-hydroxyl groups enables MEM removal using B-bromocatecholborane. Deacetylation generates the parent nucleoside, 2'-C-beta-flurormethyluridine.

摘要

[反应：见正文] 2'-C-β-氟甲基尿苷（17）既是一种潜在的重要生物制剂，也是一种生化分析工具。本文我们描述了从尿苷出发首次合成该化合物的方法。关键步骤包括用甲氧基乙氧基甲基（MEM）氯保护尿嘧啶碱基，转化为相应的2'-C-α-环氧化物，以及用氟化钾/氟化氢对环氧乙烷环进行区域选择性开环。随后对3'-和5'-羟基进行乙酰化，使得能够使用B-溴邻苯二酚硼烷脱除MEM。脱乙酰化生成母体核苷2'-C-β-氟甲基尿苷。