Total Synthesis of Isodaphlongamine H: A Possible Biogenetic Conundrum |
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Authors: | Dr Amit Kumar Chattopadhyay Vu Linh Ly Dr Shashidhar Jakkepally Dr Gilles Berger Prof Dr Stephen Hanessian |
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Institution: | Department of Chemistry, Université de Montréal, Montréal, Qc, Canada |
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Abstract: | Herein we describe the first synthetic efforts toward the total synthesis of isodaphlongamine H, a calyciphylline B‐type alkaloid. The strategy employs a chemoenzymatic process for the preparation of a functionalized cyclopentanol with a quaternary center. This molecule is elaborated to form an enantiopure 1‐aza‐perhydrocyclopentalene core, representing rings A and E of all calyciphylline B‐type alkaloids. Further transformations involve the formation of a cyclic enaminone, 1,4‐conjugate addition with a cyclopentenyl subunit, and intramolecular aldol cyclization to achieve a pentacyclic intermediate, ultimately forming isodaphlongamine H in a total of 24 steps from the commercially available compound 2‐carbethoxycyclopentanone. Isodaphlongamine H exhibits promising inhibitory activity against a panel of human cancer cell lines. |
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Keywords: | alkaloids deoxycalyciphylline B enaminones natural products total synthesis |
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