- 著者
-
Miyuki Konya
Shiho Arima
Daiki Lee
Masaki Ohtawa
Kenta Shimoyama
Takashi Fukuda
Ryuji Uchida
Hiroshi Tomoda
Noriyuki Yamaotsu
Nobutada Tanaka
Tohru Nagamitsu
- 出版者
- The Pharmaceutical Society of Japan
- 雑誌
- Chemical and Pharmaceutical Bulletin (ISSN:00092363)
- 巻号頁・発行日
- vol.70, no.4, pp.261-268, 2022-04-01 (Released:2022-04-01)
- 参考文献数
- 19
- 被引用文献数
-
3
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.