title: Total Synthesis of Isodaphlongamine H: A Possible Biogenetic Conundrum.
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.
authors.affiliation: Department of Chemistry, Université de Montréal, Station Centre Ville, C.P. 6128, Montréal, Qc, H3C 3J7, Canada.
authors.forename: Amit Kumar
authors.initials: AK
authors.lastname: Chattopadhyay
authors.affiliation: Department of Chemistry, Université de Montréal, Station Centre Ville, C.P. 6128, Montréal, Qc, H3C 3J7, Canada.
authors.forename: Vu Linh
authors.initials: VL
authors.lastname: Ly
authors.affiliation: Department of Chemistry, Université de Montréal, Station Centre Ville, C.P. 6128, Montréal, Qc, H3C 3J7, Canada.
authors.forename: Shashidhar
authors.initials: S
authors.lastname: Jakkepally
authors.affiliation: Department of Chemistry, Université de Montréal, Station Centre Ville, C.P. 6128, Montréal, Qc, H3C 3J7, Canada.
authors.forename: Gilles
authors.initials: G
authors.lastname: Berger
authors.affiliation: Department of Chemistry, Université de Montréal, Station Centre Ville, C.P. 6128, Montréal, Qc, H3C 3J7, Canada. stephen.hanessian@umontreal.ca.
authors.forename: Stephen
authors.initials: S
authors.lastname: Hanessian
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D008958:Models, Molecular
chemical_list: D000470:Alkaloids; C000611662:isodaphlongamine H
keywords: alkaloids; deoxycalyciphylline B; enaminones; natural products; total synthesis