Strategies for the Production of Vinblastine

Bis-indole dimeric alkaloids vinblastine 1 and vincristine 3 (Fig. 1) are now well accepted in the treatment of various cancers in man. These medicinally important alkaloids are obtained only from the leaves of Catharanthus roseus and the yields are extremely low. Massive amount of plant material (one ton) has to be worked up to provide few grams of these compounds. Consequently, these drugs are amongst the most expensive compounds on the pharmaceutical market. Their complex chemical structure precludes efficient chemical synthesis. Their chemotherapeutic importance has given impetus to both synthetic and biosynthetic studies of these compounds. Several research groups have investigated and are still investigating the efficient production of vinblastine type compounds using various approaches. Studies so far carried out encompass partial synthesis, biomimetic synthesis, biosynthetic investigations and efforts to isolate and purify enzymes responsible for each biosynthetic step leading to bis-indole alkaloids. I have had the chance to participate in these research projects while I was in Edinburgh, U.K. in 1981-82 and later on in Texas A&M University, U.S.A. during 1990-91 in Prof. Scott’s group. I am therefore in a position to discuss some recent advances in the field of vinblastine (VLB) synthesis.