Toward the total synthesis of bryostatin 1: Synthesis of the northern fragment (C1-C16)

ORGN 429

Hassan Seradj, shseradj@wisc.edu, Department of Chemistry, Univeristy of Wisconsin-Madison, 1101 University Ave., Madison, WI 53706, Eric A. Voight, and Steven D. Burke, burke@chem.wisc.edu, Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, WI 53706.
Bryostatin 1, a member of the bryostatin family of the natural products and currently in phase II clin. trials, has shown very promising anticancer activity. The complexity and scarcity of this compd. and other bryostatins have motivated a large no. of synthetic efforts towards these natural products. In this work, our novel approach for the synthesis of the bryostatin 1 northern fragment (C1-C16) will be presented. This approach includes a sequential ketalization/ring-closing metathesis strategy to make the A ring and an efficient hetero Diels-Alder reaction to construct the B ring. Further elaboration gives the fully functionalized northern fragment (C1-C16) in 23 steps (longest linear sequence) from commercially available starting compounds. Efforts towards the coupling of the fragments using a short and efficient endgame strategy will be discussed.