Alkaloids of Vinca rosea Linn. (Catharanthus roseus G. Don.) V.**Organic Chemical Development and Lilly Research Laboratories, Eli Lilly and Co., Indianapolis, Ind.

Stereocontrolled total synthesis of (+)-vincristine

“…In this work, we describe a total synthesis of vincristine (2) through the stereoselective coupling of demethylvindoline and the eleven-membered carbomethoxyverbanamine presursor. This is a previously unreported example of de novo total synthesis of vincristine (2) without dependence on either derivatization of vinblastine (1) or semisynthesis with vindoline (3).…”

“…Independently, researchers at Eli Lilly found that extracts of C. roseus possessed activity against P-1534 leukemia in mice and isolated vinblastine as its active entity in 1959 (2). The structure of a related compound, vincristine methiodide, was then determined by an x-ray crystallography in 1965 (3).…”

“…Vinblastine (1) is mainly useful for treating lymphocytic lymphoma, histiocytic lymphoma, Kaposi's sarcoma, and advanced testicular and breast cancer. Vincristine (2), on the other hand, displays curative effects in acute leukemia, rhabdomyosarcoma, neuroblastoma, and other lymphomas. Clinical treatment with these alkaloids is commonly accompanied by toxic side effects, and the typical dose-limiting factor for the former is bone marrow damage and the dose-limiting factor for the latter is neurotoxicity.…”

“…In contrast, vincristine (2), which is more difficult to obtain than vinblastine (1) because of very low content in the plant (Ϸ0.0003% yield from C. roseus),…”

Conversion of Vindoline into 11-Mesyloxytabersonine

“…1), such as conophylline (1) 3-7) and vinblastine (2). 8,9) Therefore, an efficient preparation of the aspidospermaskeleton is important for the synthesis of novel analogs of these indole alkaloids.…”