Evolution of Synthetic Strategies for Highly Functionalized Natural Products: A Successful Route to Bryostatin 3

A convergent asymmetric synthesis of the antineoplastic marine macrolide, bryostatin 3 (1), has been achieved. This synthesis relied upon stereo-controlled construction of two major fragments, the top-half fragment 2 and the bottom half fragment 3, and their coupling by the Julia–Lythgoe olefination and Yamaguchi macrolactonization. The top-half fragment 2 could successfully be synthesized by tandem connection of the three key fragments. The bottom-half fragment 3 was prepared by the union of vinyl iodide 39 and α-alkoxy aldehyde 30.