Total Syntheses of Bryostatins: Synthesis of Two Ring-Expanded Bryostatin Analogues and the Development of a New-Generation Strategy to Access the C7–C27 Fragment

摘要

Herein, we report the synthesis of novel ring-expanded bryostatin analogues. By carefully modifying the substrate, a selective and high-yielding Ru-catalyzed tandem enyne coupling/Michael addition was employed to construct the northern fragment. Ring-closing metathesis was utilized to form the 31-membered ring macrocycle of the analogue. These ring-expanded bryostatin analogues possess anticancer activity against several cancer cell lines. Given the difficulty in forming the C16–C17 olefin at a late stage, we also describe our development of a new-generation strategy to access the C7–C27 fragment, containing both the ring B and C subunits.