一种制备正交O-保护的2-脱氧链霉胺的简短且可扩展的方法。

A short and scalable route to orthogonally O-protected 2-deoxystreptamine.

作者信息

van den Broek Sebastiaan Bas A M W, Gruijters Bas W T, Rutjes Floris P J T, van Delft Floris L, Blaauw Richard H

机构信息

Chiralix B.V., P.O. Box 31070, 6503 CB Nijmegen, The Netherlands.

出版信息

J Org Chem. 2007 Apr 27;72(9):3577-80. doi: 10.1021/jo062369y. Epub 2007 Mar 27.

DOI:10.1021/jo062369y

PMID:17385914

Abstract

A seven-step synthesis of orthogonally O-protected 2-deoxy-streptamine has been developed from readily available neomycin, with an overall yield of 28%. Key chemical transformations include a chemoselective glycosidic bond hydrolysis and two regioselective protective group manipulations involving acetylation and deacetylation. The synthetic route is amenable to scale-up for the production of multigram quantities of enantiopure and orthogonally O-protected 2-deoxystreptamine, a versatile scaffold for the generation of libraries of RNA-targeting ligands.

摘要

已开发出一种从易于获得的新霉素出发，经七步合成正交O-保护的2-脱氧链霉胺的方法，总产率为28%。关键的化学转化包括化学选择性糖苷键水解以及涉及乙酰化和脱乙酰化的两个区域选择性保护基操作。该合成路线适合放大生产多克量的对映体纯且正交O-保护的2-脱氧链霉胺，这是一种用于生成RNA靶向配体文库的通用骨架。