Gordon H. Svoboda

Chapter 34. Alkaloids

Publisher Summary This chapter elaborates the development of alkaloids possessing clinical activity. The complete molecular structure, including the stereochemistry and the absolute configuration of leurocristine methiodide dihydrate, has been determined by the combination of two crystallographic methods based on the anomalous scattering of X-rays. The elucidation of the structures of vincaleukoblastine and leurocristine allows for a rational and systematic approach to their synthesis, as well as for a logical pursuit of structure–activity relationships. The most interesting alkaloid isolated from the Australian scrub ash is acronycine. The experimental systems of special interest which are responsive to this alkaloid include X-5563 plasma cell myeloma, a model system of multiple myeloma in man, Shionogi carcinoma 115, an androgen-dependent tumor, potentially a model system for prostatic cancer, and the C-1498 myelogenous leukemia which is nonresponsive to any of the clinically useful chemotherapeutic agents. Camptothecin is active against the L-1210 leukemia and the Walker 256 carcinosarcoma. A number of unusual dimeric indole alkaloids have also been studied and structures have been postulated primarily on the basis of interpretation of physical data.