Synthesis of C-15 vindoline analogues by palladium-catalyzed cross-coupling reactions.
Described are general protocols for the rapid construction of various C-15-substituted analogues of vindoline using palladium-catalyzed cross-coupling reactions. The required bromo- and iodovindolines were prepared in high yield by the reaction of vindoline with N-bromosuccinimide or N-iodosuccinimide, respectively. The study not only led to the preparation of a number of structurally novel vindoline analogues but also opens the door to new strategies for the synthesis of vinblastine, vincristine, and related anticancer agents. Also described is the conversion of ent-tabersonine to ent-vindoline.
Johnson
Peter D
PD
Department of Chemistry, University of Chicago, Chicago, Illinois 60637, USA.
Sohn
Jeong-Hun
JH
Rawal
Viresh H
VH
D000970:Antineoplastic Agents / Q000138:chemical synthesis; D002384:Catalysis; D026121:Indole Alkaloids / Q000737:chemistry; D008722:Methods; D010165:Palladium / Q000737:chemistry; D011804:Quinolines / Q000737:chemistry; D013388:Succinimides / Q000737:chemistry; D014747:Vinblastine / Q000031:analogs & derivatives* / Q000138:chemical synthesis
D000970:Antineoplastic Agents; D026121:Indole Alkaloids; D011804:Quinolines; D013388:Succinimides; C009373:tabersonine; C009667:vindoline; D010165:Palladium; D014747:Vinblastine