Wu Kelvin J Y, Tresco Ben I C, Xiao Junzhe, See Dominic N Y, Myers Andrew G
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, United States.
J Am Chem Soc. 2024 Oct 23;146(42):29135-29139. doi: 10.1021/jacs.4c11270. Epub 2024 Oct 12.
Scalable syntheses of the northern macrobicyclic thiolincosamine fragments of two structurally complex antibiotic candidates, BT-33 and cresomycin, are presented. A key transformation in each route is the highly diastereoselective addition of a putative allenylzinc nucleophile to a common Ellman sulfinimine intermediate using a zinc-promoted Barbier-type propargylation protocol that is detailed herein. These transformations proceed with dynamic kinetic resolution and use just 1.2 equiv of each respective propargyl bromide precursor.
本文介绍了两种结构复杂的抗生素候选物BT-33和新月霉素的大环硫代林肯胺片段的可扩展合成方法。每条路线中的关键转化步骤是,使用本文详细介绍的锌促进的巴比耶型炔丙基化协议,将假定的烯丙基锌亲核试剂以高度非对映选择性的方式加成到一个常见的埃尔曼亚磺酰亚胺中间体上。这些转化过程通过动态动力学拆分进行,每种炔丙基溴前体仅使用1.2当量。