水中含脯氨酸残基的二酮哌嗪的构象变化和差向异构化

Conformational Change and Epimerization of Diketopiperazines Containing Proline Residue in Water.

作者信息

Ishizu Takashi, Tsutsumi Hiroyuki, Yokoyama Emi, Kawamoto Haruka, Yokota Runa

机构信息

Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University.

出版信息

Chem Pharm Bull (Tokyo). 2017;65(6):598-602. doi: 10.1248/cpb.c17-00164.

DOI:10.1248/cpb.c17-00164

PMID:28566652

Abstract

In water, diketopiperazines cyclo(L-Pro-L-Xxx) and cyclo(L-Pro-D-Xxx) (Xxx=Phe, Tyr) formed an intramolecular hydrophobic interaction between the main skeleton part and their benzene ring, and both cyclo(L-Pro-L-Xxx) and cyclo(L-Pro-D-Xxx) took a folded conformation. The conformational changes from folded to extended conformation by addition of several deuterated organic solvents (acetone-d, metanol-d, dimethyl sulfoxide-d (DMSO-d)) and the temperature rise were investigated using H-NMR spectra. The results suggested that the intrarmolecular hydrophobic interaction of cyclo(L-Pro-D-Xxx) formed more strongtly than that of cyclo(L-Pro-L-Xxx). Under a basic condition of 1.0×10 mol/L potassium deuteroxide, enolization of O-C-C-H moiety of cyclo(L-Pro-L-Xxx) occurred, while that of the O-C-C-H moiety did not. Cyclo(L-Pro-L-Xxx) epimerized to cyclo(D-Pro-L-Xxx), while cyclo(L-Pro-D-Xxx) did not change.

摘要

在水中，二酮哌嗪环（L-脯氨酸-L-XXX）和环（L-脯氨酸-D-XXX）（XXX = 苯丙氨酸、酪氨酸）在主骨架部分与其苯环之间形成分子内疏水相互作用，且环（L-脯氨酸-L-XXX）和环（L-脯氨酸-D-XXX）均呈折叠构象。利用氢核磁共振谱研究了通过添加几种氘代有机溶剂（丙酮-d、甲醇-d、二甲亚砜-d（DMSO-d））以及温度升高导致的从折叠构象到伸展构象的构象变化。结果表明，环（L-脯氨酸-D-XXX）的分子内疏水相互作用比环（L-脯氨酸-L-XXX）的形成更强。在1.0×10⁻³摩尔/升氘氧化钾的碱性条件下，环（L-脯氨酸-L-XXX）的O-C-C-H部分发生烯醇化，而O-C-C-H部分未发生。环（L-脯氨酸-L-XXX）差向异构化为环（D-脯氨酸-L-XXX），而环（L-脯氨酸-D-XXX）未发生变化。