螺内酰胺作为构象受限的拟肽：合成与构象分析

Spirolactams as conformationally restricted pseudopeptides: synthesis and conformational analysis.

作者信息

Fernández M Montserrat, Diez Anna, Rubiralta Mario, Montenegro Elvira, Casamitjana Núria, Kogan Marcelo J, Giralt Ernest

机构信息

Departament de Química Orgànica, Facultat de Química, Universitat de Barcelona, c/Martí i Franquès, Spain.

出版信息

J Org Chem. 2002 Nov 1;67(22):7587-99. doi: 10.1021/jo025999i.

DOI:10.1021/jo025999i

PMID:12398477

Abstract

The synthesis of 1-(tert-butoxycarbonyl)-7-[1-(tert-butoxycarbonyl)-3-methylbutyl]-6-oxo-1,7-diazaspiro[4.5]decanes (S,S)-1a and (S,R)-1b is described. Derivatives 17a,b and 19a are prepared for use in peptide synthesis as constrained surrogates of the Pro-Leu and Gly-Leu dipeptides. The Ac-[Gly-Leu]-Met-NH(2) derivatives (S,S,S)-2a and (S,R,S)-2b, with the tripeptidic C-terminal region present in tachykinins, are also synthesized. Conformational analyses of these tripetide analogues by NMR experiments and molecular modeling calculations show that both (S,S,S)-2a and (S,R,S)-2b epimers are gamma-turn/distorted type II beta-turn mimetics.

摘要

本文描述了1-(叔丁氧羰基)-7-[1-(叔丁氧羰基)-3-甲基丁基]-6-氧代-1,7-二氮杂螺[4.5]癸烷(S,S)-1a和(S,R)-1b的合成。制备了衍生物17a、b和19a，用于肽合成，作为Pro-Leu和Gly-Leu二肽的受限替代物。还合成了具有速激肽中存在的三肽C端区域的Ac-[Gly-Leu]-Met-NH₂衍生物(S,S,S)-2a和(S,R,S)-2b。通过NMR实验和分子建模计算对这些三肽类似物进行的构象分析表明，(S,S,S)-2a和(S,R,S)-2b差向异构体均为γ-转角/扭曲型IIβ-转角模拟物。