Premium
Total Synthesis of Isodaphlongamine H: A Possible Biogenetic Conundrum
Author(s) -
Chattopadhyay Amit Kumar,
Ly Vu Linh,
Jakkepally Shashidhar,
Berger Gilles,
Hanessian Stephen
Publication year - 2016
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201510861
Subject(s) - enantiopure drug , stereochemistry , aldol reaction , chemistry , total synthesis , intramolecular force , conjugate , combinatorial chemistry , enantioselective synthesis , organic chemistry , mathematics , catalysis , mathematical analysis
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.