Stereocontrolled total synthesis of (+)-vincristine

2004/05/12 by Takeshi Kuboyama, Satoshi Yokoshima, Hidetoshi Tokuyama +1 · 3 citations
Chemistry · Pharmacology, Toxicology and Pharmaceutics · Medicine · #Chemical synthesis and alkaloids #Alkaloids: synthesis and pharmacology #Cancer Treatment and Pharmacology

paper · doi:10.1073/pnas.0401323101

openalex publication_date 2004/05/12 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/22

Abstract

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.

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