Ishizu Takashi, Tsutsumi Hiroyuki, Yokoyama Emi, Kawamoto Haruka, Yokota Runa
Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University.
Chem Pharm Bull (Tokyo). 2017;65(6):598-602. doi: 10.1248/cpb.c17-00164.
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.
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。
