Stereoselective Synthesis of Baulamycin A
Jonathan R. Thielman, David H. Sherman, Robert M. Williams
Abstract
New structural classes of antibiotics are rare, structurally novel broad-spectrum antibiotics exceptionally so. The recently discovered baulamycins constitute a remarkable example of these highly prized compounds and, as such, have attracted considerable attention in the form of both synthetic efforts and biological studies. For the first time, we report a gram-scale preparation of the common carbon framework of the baulamycin family, as well as the total synthesis of its most potent member, baulamycin A. Our approach employs highly stereoselective, catalyst-controlled asymmetric conjugate additions to thioesters to set key stereocenters, as well as the first reported use of "dry ozonolysis" to reveal a masked carboxylic acid in the total synthesis of a natural product.