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

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.