Probing the ribosomal RNA A-site with functionally diverse analogues of paromomycin - synthesis of ring I mimetics

被引：10

作者：

Hanessian, Stephen

Adhikari, Susanta

Szychowski, Janek

Pachamuthu, Kandasmy

Wang, Xiaojing

Migawa, Michael T.

Griffey, Richard H.

Swayze, Eric E.

机构：

[1] Univ Montreal, Dept Chem, Montreal, PQ H3C 3J7, Canada

[2] Scios Inc, Fremont, CA 94555 USA

[3] Isis Pharmaceut Inc, Carlsbad, CA 92008 USA

来源：

TETRAHEDRON | 2007年 / 63卷 / 04期

基金：

加拿大自然科学与工程研究理事会;

关键词：

D O I：

10.1016/j.tet.2006.10.079

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

Methods were developed to selectively cleave the 2-amino-2-deoxy-alpha-D-glucopyranosyl ring in paromomycin. The preferentially N- and O-protected products were alkylated on the liberated C4 hydroxyl group of the deoxystreptalnine subunit. Further manipulation furnished a series of aromatic, heteroaromatic, and aliphatic appendages as spatial mimics offing 1. Modest inhibitory activity was found against Staphylococcus aureus with two analogues (27 and 63), although cell-free functional transcription/translation assays were similar to paromomycin for analogue 27. (c) 2006 Elsevier Ltd. All rights reserved.

引用

页码：827 / 846

页数：20

共 80 条

[1] Probing the specificity of aminoglycoside ribosomal RNA interactions with designed synthetic analogs [J].