Bryostatins, polyether macrolides isolated from the marine bryozoans Bugula neritina L. and Amathia convouta, have remarkably powerful antineoplastic activities and the potential to promote kinase C activity attracting the interest of many synthetic chemists. In particular, bryostatin 1 is now undergoing the Phase II clinical test in National Caner Institute and is recognized as a promising anticancer agent. From the biological and synthetic points of view, synthetic studies on bryostatins, particularly bryostatin 3, have been carried out. Based on the retrosynthesis of bryostatin 3 (1) (Scheme 1), we first synthesized the two segments, the top-half fragment (2) and the bottom-half fragment (3). Using Julia-Lythgoe olefination method, coupling of the two segments afforded the seco-acid derivative, which had the same functional groups as those of bryostatin 3 except for the C_<13> functionality. The following macrolactonization afforded the desired lactone (18), which presumably adopts a keto form at the C_9 position. Further synthetic study on bryostatin 3 is in progress.
