ASYMMETRIC SYNTHESIS OF C10-C27 SEGMENT OF BRYOSTATIN 1

Stanford University, Stanford CA

Investigators

Abstract

The proposed work on bryostatin 1 focuses on the efficient synthesis of two of the three ring systems which contain exocyclic olefins. The stereoselective installation of these bonds has been problematic and is often postponed until late in the synthesis. Moderate to poor diastereoselectivities and yields are typical. The synthesis highlights Pd-catalyzed internal/terminal alkyne cross-couplings as a potential efficient solution to this problem. No existing approaches utilize Pd in the construction of these tetrahydropyrans. Bryostatin 1 provides a unique opportunity to demonstrate the prowess of this method with complex alkynes derived from readily available starting materials. This key transformation demonstrates the theme of atom economy, and should result in increased efficiency over existing routes toward this target.