Preferred secondary structures as a possible driving force for macrocyclization

被引：10

作者：

Reyes, S ^{[1
]}

Pattarawarapan, M ^{[1
]}

Roy, S ^{[1
]}

Burgess, K ^{[1
]}

机构：

[1] Texas A&M Univ, Dept Chem, College Stn, TX 77843 USA

来源：

TETRAHEDRON | 2000年 / 56卷 / 50期

关键词：

SNAr; macrocyclizations; beta-turns; solid phase synthesis;

D O I：

10.1016/S0040-4020(00)00888-7

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

The purpose of the work described in this paper was to explore links that may exist between conformational bias in macrocyclic products and the ease with which they are formed in solid phase SNAr reactions. Solid phase synthesis of compounds 2 proceeds more efficiently than of compounds 3 under similar conditions. Compounds 2 were designed to mimic p-turn conformations in the dipeptide residues whereas compounds 3 were thought to be unable to show a similar conformational preference. The second assertion was shown to be correct but, surprisingly, CD, NMR, and molecular simulation experiments for 2a indicate another conformation is preferred in solution. This may involve H-bonding of the asparagine side-chain to a backbone amide-carbonyl. Molecular dynamics simulations indicate that cyclization to form compound 2a is statistically more favorable than that to form 3a. (C) 2000 Elsevier Science Ltd. All rights reserved.

引用

页码：9809 / 9818

页数：10

共 23 条

[1] An efficient β-turn directed cyclization of simple peptidomimetics [J].