文章基本信息

标题：Synthesis and Evaluation of Habiterpenol Analogs
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作者：Miyuki Konya ; Shiho Arima ; Daiki Lee 等
期刊名称：Chemical and Pharmaceutical Bulletin
印刷版ISSN：0009-2363
电子版ISSN：1347-5223
出版年度：2022
卷号：70
期号：4
页码：261-268
DOI：10.1248/cpb.c21-00993
语种：English
出版社：The Pharmaceutical Society of Japan
摘要：Habiterpenol is a G2 checkpoint inhibitor isolated from the culture broth of Phytohabitans sp. 3787_5. Here, we report the synthesis of new habiterpenol analogs through the total synthesis process of habiterpenol and evaluating the analogs for G2 checkpoint inhibitory activity. We investigated two different synthetic approaches for total synthesis, with intramolecular conjugate addition and Ti(III)-mediated radical cyclization as key reactions. Although the former was unsuccessful, the latter reaction facilitated stereoselective total synthesis and determination of the absolute configuration of habiterpenol. The extension of these chemistries to a structure–activity relationship (SAR) study gave new habiterpenol analogs, which could not be derived from natural habiterpenol and only be synthesized by applying the total synthesis. Therefore, this study provides important insights into SAR studies of habiterpenol.
关键词：habiterpenol;total synthesis;G2 checkpoint inhibitor;structure–activity relationship study