由二取代3-(氨基乙氧基)丙酸连接体约束的二肽的合成与构象研究

Synthesis and conformational studies of dipeptides constrained by disubstituted 3-(aminoethoxy)propionic acid linkers.

作者信息

Reddy D Srinivasa, Vander Velde David, Aubé Jeffrey

机构信息

Department of Medicinal Chemistry, 1251 Wescoe Hall Drive, Malott Hall, Room 4070, University of Kansas, Lawrence, Kansas 66045-7582, USA.

出版信息

J Org Chem. 2004 Mar 5;69(5):1716-9. doi: 10.1021/jo035683q.

DOI:10.1021/jo035683q

PMID:14987032

Abstract

A series of cyclic compounds with dimethyl-substituted 3-(aminoethoxy)propionic acid linkers have been prepared as potential beta-turn mimics. The desired linkers were prepared from disubstituted pyrones, which were coupled with dipeptides and then subjected to macrocyclization using diethylcyanophosphonate to furnish cyclic compounds 1-5. Conformational analysis was carried out using NMR and X-ray crystallography. All of the five cyclic compounds were found to exist in type I or type II beta-turn conformations.

摘要

一系列带有二甲基取代的3-(氨基乙氧基)丙酸连接基的环状化合物已被制备出来作为潜在的β-转角模拟物。所需的连接基由二取代吡喃酮制备，将其与二肽偶联，然后使用氰基磷酸二乙酯进行大环化反应以提供环状化合物1-5。使用核磁共振和X射线晶体学进行构象分析。发现所有这五种环状化合物均以I型或II型β-转角构象存在。