Synthesis of (2R,8′S,3′E)-δ-tocodienol, a tocoflexol family member designed to have a superior pharmacokinetic profile compared to δ-tocotrienol

详细信息    查看全文

• 作者：Xingui Liu ; Satheesh Gujarathi ; Xuan Zhang ; Lijian Shao ; Marjan Boerma ; Cesar M. Compadre ; Peter A. Crooks ; Martin Hauer-Jensen ; Daohong Zhou ; Guangrong Zheng ; ^{gzheng@uams.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Tocotrienol ; Tocodienol ; Oxidative olefin cleavage ; C&ndash ; C coupling ; Desulfonylation
• 刊名：Tetrahedron
• 出版年：2016
• 出版时间：7 July 2016
• 年：2016
• 卷：72
• 期：27-28
• 页码：4001-4006
• 全文大小：610 K

文摘

A group of side chain partially saturated tocotrienol analogues, namely tocoflexols, have been previously designed in an effort to improve the pharmacokinetic properties of tocotrienols. (2R,8′S,3′E)-δ-Tocodienol (1) was predicted to be a high value tocoflexol for further pharmacological evaluation. We now report here an efficient eight-step synthetic route to compound 1 utilizing naturally-occurring δ-tocotrienol as a starting material (24% total yield). The key step in the synthesis is oxidative olefin cleavage of δ-tocotrienol to afford the chroman core of 1 with retention of chirality at the C-2 stereocenter.