Stereocontrolled total synthesis of (+)-vincristine.
An efficient total synthesis of (+)-vincristine has been accomplished through a stereoselective coupling of demethylvindoline and the eleven-membered carbomethoxyverbanamine presursor. Demethylvindoline was prepared by oxidation of 17-hydroxy-11-methoxytabersonine, followed by regioselective acetylation with mixed anhydride method. Although an initial attempt of coupling by using demethylvindoline formamide was not successful and resulted in recovery of the starting compounds, the reaction using demethylvindoline took place smoothly to furnish the desired bisindole product with the correct stereochemistry at C18'. After formation of the piperidine ring by sequential removal of the protective groups and intramolecular nucleophilic cyclization, the total synthesis of vincristine was completed by formylation of N1.
Kuboyama
Takeshi
T
Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-033, Japan.
Yokoshima
Satoshi
S
Tokuyama
Hidetoshi
H
Fukuyama
Tohru
T
D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis / Q000737:chemistry; D002625:Chemistry, Organic / Q000379:methods; D015394:Molecular Structure; D013237:Stereoisomerism; D014750:Vincristine / Q000138:chemical synthesis* / Q000737:chemistry
D000972:Antineoplastic Agents, Phytogenic; D014750:Vincristine