耶鲁大学Seth B. Herzon课题组近日取得一项新成果。经过不懈努力，他们发展了合成含碱性氮的α-或β-脱氧氨基糖苷的普适方法。2021年2月8日出版的《美国化学会杂志》发表了这项成果。

在本文中，该课题组提出了一种从常见前体合成α-或β-2,3,6-三脱氧-3-氨基-和2,4,6-三脱氧-4-氨基的O-糖苷的方法。他们的策略首先对噻吩糖苷供体还原性锂化，然后对生成的异头阴离子用2-甲基四氢吡喃过氧化物进行捕获。研究团队将此策略应用于以伯/仲过氧化物为亲电子试剂的α-和β-山梨糖胺，吡咯烷胺，二十二胺和香豆素衍生物的合成中。

α-连接的产物收率为60-96%，选择性>50:1. β-连接的产物收率为45-94%，手性选择性为1.7→50:1。与带有eq氨基取代基的供体相反，带有ax氨基取代基的供体在低温下更倾向于生成β-产物。该工作建立了合成含碱性氮的O-糖苷的普适策略。

据悉，由于氨基与路易斯酸促进剂的竞争性配位，通过传统的路易斯酸引入含碱性氮的糖苷具有一定挑战性。另外，由于许多氨基糖苷缺乏C2取代基，因此经常在反应中生成O-糖苷的非对映异构混合物。

附：英文原文

Title: General Method for the Synthesis of α- or β-Deoxyaminoglycosides Bearing Basic Nitrogen

Author: Kevin M. Hoang, Nicholas R. Lees, Seth B. Herzon

Issue&Volume: February 8, 2021

Abstract: The introduction of glycosides bearing basic nitrogen is challenging using conventional Lewis acid-promoted pathways owing to competitive coordination of the amine to the Lewis acid promoter. Additionally, because many aminoglycosides lack a C2 substituent, diastereomeric mixtures of O-glycosides are often produced. Herein, we present a method for the synthesis of α- or β- 2,3,6-trideoxy-3-amino- and 2,4,6-trideoxy-4-amino O-glycosides from a common precursor. Our strategy proceeds by the reductive lithiation of thiophenyl glycoside donors and trapping of the resulting anomeric anions with 2-methyltetrahydropyranyl peroxides. We apply this strategy to the synthesis of α- and β-forosamine, pyrrolosamine, acosamine, and ristosamine derivatives using primary and secondary peroxides as electrophiles. α-Linked products are obtained in 60–96% yield and with >50:1 selectivity. β-Linked products are obtained in 45–94% yield and with 1.7–>50:1 stereoselectivity. Contrary to donors bearing an equatorial amine substituent, donors bearing an axial amine substituent favored β-products at low temperatures. This work establishes a general strategy to synthesize O-glycosides bearing a basic nitrogen.

DOI: 10.1021/jacs.0c11262

Source: https://pubs.acs.org/doi/10.1021/jacs.0c11262