Thielman Jonathan R, Sherman David H, Williams Robert M
Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523, United States.
Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109, United States.
J Org Chem. 2020 Mar 6;85(5):3812-3823. doi: 10.1021/acs.joc.9b03443. Epub 2020 Feb 7.
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.
新型抗生素结构类别稀少，结构新颖的广谱抗生素更是如此。最近发现的鲍拉霉素就是这类备受珍视化合物的一个显著例子，因此，在合成研究和生物学研究方面都引起了相当大的关注。我们首次报道了鲍拉霉素家族共同碳骨架的克级制备，以及其最具活性成员鲍拉霉素A的全合成。我们的方法采用高度立体选择性、催化剂控制的硫酯不对称共轭加成来构建关键立体中心，以及首次报道在天然产物全合成中使用“干式臭氧分解”来揭示一个被掩盖的羧酸。
