Synthesis and library construction of privileged tetra-substituted ∆5-2-oxopiperazine as β-turn structure mimetics

Δ5-2-oxopiperazine;Synthesis;Library construction;합성;라이브러리 구축;생체유사Mimetics;571

자연과학대학 생물물리 및 화학생물학과 ;

University:서울대학교 대학원

关键词: Δ5-2-oxopiperazine;    Synthesis;    Library construction;    합성;    라이브러리 구축;    생체유사Mimetics;    571;   

Others  :  http://s-space.snu.ac.kr/bitstream/10371/131525/1/000000020812.pdf

美国|英语

来源: Seoul National University Open Repository

【 摘 要 】

In this study, we developed an efficient and practical procedure for the synthesis of tetra-substituted ∆5-2-oxopiperazine that mimics the bioactive β-turn structural motif of proteins. This synthetic route is robust and modular enough to accommodate 4 different substituents to obtain a high level of molecular diversity without any deterioration in stereochemical enrichment of the natural and unnatural amino acids. Through the in silico studies, including a distance calculation of side chains and a conformational overlapping of our model compound with a native β-turn structure, we successfully demonstrated the conformational similarity of tetra-substituted ∆5-2-oxopiperazine to the β-turn motif. For the library construction in a high-throughput manner, the fluorous tag technology was adopted with the use of a solution-phase parallel synthesis platform. A 140-membered pilot library of tetra-substituted ∆5-2-oxopiperazines was achieved with an average purity of 90% without further purification.