Chemo- and Regioselective Functionalization of Nortrilobolide: Application for Semisynthesis of the Natural Product 2-Acetoxytrilobolide

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• 作者：Nhu Thi Quynh Doan ; Fran莽ois Crestey ; Carl Erik Olsen ; S酶ren Br酶gger Christensen
• 刊名：Journal of Natural Products
• 出版年：2015
• 出版时间：June 26, 2015
• 年：2015
• 卷：78
• 期：6
• 页码：1406-1414
• 全文大小：429K
• ISSN：1520-6025

文摘

The difference in reactivity of the hexaoxygenated natural product thapsigargin (1) and the pentaoxygenated nortrilobolide (3) was compared in order to develop a chemo- and regioselective method for the conversion of nortrilobolide (3) into the natural product 2-acetoxytrilobolide (4). For the first time, a stereoselective synthesis of 2-acetoxytrilobolide (4) is described, which involves two key reactions: the first chemical step was a one-pot substitution鈥搊xidation reaction of an allylic ester into its corresponding 伪,尾-unsaturated ketone. The second process consisted of a stereoselective 伪鈥?acyloxylation of the key intermediate 伪,尾-unsaturated ketone to afford its corresponding acetoxyketone, which was converted into 2-acetoxytrilobolide (4) in a few steps. This innovative approach would allow the synthesis of a broad library of novel and valuable penta- and hexaoxygenated guaianolides as potential anticancer agents.