Bufadienolide type steroid

Palladium-mediated cross-coupling of 2-pyrone-5-boronate (63), prepared by coupling of 5-bromo-2-pyrone with pinacol borane (30), with a range of androster-one-derived alkenyl triflates 64 affords bufadienolide type steroids 65 in high yields (Scheme 3.29) [47]. 

Earlier, some of the same considerations had led me in 1957 to initiate a study of amphibian venoms of the steroidal bufadienolide (6) type as potential sources of new antineoplastic substances. Eventually we found that some of the toad venom bufadienolides such as marinobufagin significantly inhibit growth of the National Cancer Institute s KB cell line derived from a human nasopharynx carcinoma and lead to a curative response with the murine Ehrlich ascites system (7). However, the therapeutic indices were unattractive for further development. So the effort was extended in 1965-66, as Just noted, to encompass a geographically far-reaching area (Asia, Africa, Australia etc.) and an extensive research program to evaluate marine invertebrates and arthropods for structurally unique and useful anticancer constituents. Subsequently we isolated the first such invertebrate antineoplastic constituents (8-12). Meanwhile, our early expectations have been abundantly realized and the discovery of the bryostatins provides a splendid illustration. 

Pregnane derivatives not only are important in their own right but also occupy a central position in steroid biochemistry since they serve as precursors of steroids possessing other types of biological activities, such as the androgenic and estrogenic hormones in vertebrates and the cardenolides, possibly also the bufadienolides (Tschesche and Brassat, 1965) and certain alkaloids in plants and animals. 

---