3-氨基内酰胺作为X-甘氨酸受限拟二肽的合成及色氨酸-甘氨酸替代物的构象研究。

Synthesis of 3-aminolactams as X-Gly constrained pseudodipeptides and conformational study of a Trp-Gly surrogate.

作者信息

Ecija Marta, Diez Anna, Rubiralta Mario, Casamitjana Núria, Kogan Marcelo J, Giralt Ernest

机构信息

Laboratori de Química Orgànica, Facultat de Farmàcia, Universitat de Barcelona, Av. Joan XXIII s/n, 08028-Barcelona, Spain, and Parc Científic de Barcelona, c/ Josep Samitier, 1-5, 08028-Barcelona, Spain.

出版信息

J Org Chem. 2003 Dec 12;68(25):9541-53. doi: 10.1021/jo035151+.

DOI:10.1021/jo035151+

PMID:14656078

Abstract

3-Amino-delta-valerolactams trans-11a-c were synthesized through conjugate addition and Curtius rearrangement and converted into Fmoc-[Trp-Gly], Fmoc-[Ile-Gly], and Fmoc-[Phe-Gly] pseudodipeptides. Conformational analyses of tripeptide analogues Ac-[Trp-Gly]-Leu-NH(2) 17a and 17b by NMR experiments and molecular modeling calculations showed that diastereomer 17a adopted a gamma-turn/distorted type II beta-turn structure, whereas diastereomer 17b adopted mainly a gamma-turn structure.

摘要

通过共轭加成和库尔提斯重排反应合成了反式-11a-c的3-氨基-δ-戊内酰胺，并将其转化为Fmoc-[色氨酸-甘氨酸]、Fmoc-[异亮氨酸-甘氨酸]和Fmoc-[苯丙氨酸-甘氨酸]假二肽。通过核磁共振实验和分子模拟计算对三肽类似物Ac-[色氨酸-甘氨酸]-亮氨酸-NH(2) 17a和17b进行构象分析，结果表明非对映异构体17a采用γ-转角/扭曲的II型β-转角结构，而非对映异构体17b主要采用γ-转角结构。