Enantioselective Total Synthesis of Mandelalide A and Isomandelalide A: Discovery of a Cytotoxic Ring-Expanded Isomer

详细信息    查看全文

• 作者：Nagarathanam Veerasamy ; Ankan Ghosh ; Jinming Li ; Kazuhiro Watanabe ; Jeffrey D. Serrill ; Jane E. Ishmael ; Kerry L. McPhail ; Rich G. Carter
• 刊名：Journal of the American Chemical Society
• 出版年：2016
• 出版时间：January 27, 2016
• 年：2016
• 卷：138
• 期：3
• 页码：770-773
• 全文大小：389K
• ISSN：1520-5126

文摘

The total synthesis of mandelalide A and its ring-expanded macrolide isomer isomandelalide A has been achieved. Unexpected high levels of cytotoxicity were observed with the ring-expanded isomandelalide A with a rank order of potency: mandelalide A > isomandelalide A > mandelalide B. Key aspects of the synthesis include Ag-catalyzed cyclizations (AgCC’s) to construct both the THF and THP rings present in the macrocycle, diastereoselective Sharpless dihydroylation of a cis-enyne, and lithium acetylide coupling with a chiral epoxide.