ChemInform Abstract: 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

This paper reports 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. A ring-closing metathesis was utilized to form the 31-membered macrocycle of the analogue. These ring-expanded bryostatin analogues possess anticancer activity against several cancer cell lines. Given the difficulty of forming the C16-17 olefin in the late stage, we also describe our development of a new-generation strategy to access the C7-C27 fragment containing both the B- and C-ring subunits.