Synthetic and Isolation Studies Towards Vinblastine and Vincristine and Their Novel derivatives

Abstract

During the first phase of the project a 3-acre farm of Catharanthus roseus plants has been grown in the Karachi University Campus which has provided a regular supply for leaves for isolation and synthetic studies. A large flash evaporator system was designed, fabricated and installed in one room of the institute building which has allowed fast and mild evaporations of 120 gallons of alcoholic extracts of the leaves per 8 hours daily. As a result of extensive isolation studies, procedure for the isolation of catharanthine, vindoline and vinblastine have been optimized and patented. A number of new alkaloids have been isolated from C. roseus which include 16-epi-19-S-vindolinine, fluorocarpamine-N-oxide, pleiocarpamine and 16-epi-19-S-vindolinine-N-oxide. The structure of these have been elucidated on the basis of I.R., U.V., PMR, CMR, mass spectrometry and chemical degradation. Synthetic approaches to the anti-tumor alkaloids are described in depths, which include new synthesis of β-carboline and gambirtannine systems which are generally recognized as the biosynthetic precursors to the Aspidosperma and Iboga groups of alkaloids. The work has resulted in 13 publications/patents, a list of which is attached at the end of the project report.