Department of Small Molecule Process Chemistry , Genentech, Inc. , 1 DNA Way , South San Francisco , California 94080 , United States.
Org Lett. 2019 Nov 15;21(22):9099-9103. doi: 10.1021/acs.orglett.9b03481. Epub 2019 Oct 31.
We report herein an efficient, stereocontrolled, and chromatography-free synthesis of the novel broad spectrum antibiotic . The route features the construction of a functionalized tripeptide backbone, a high-yielding macrocyclization via a Pd-catalyzed Suzuki-Miyaura reaction, and the late-stage elaboration of key amide bonds with minimal stereochemical erosion. Through extensive reaction development and analytical understanding, these key advancements allowed the preparation of in 17 steps, 15% overall yield, >99 A % HPLC, and >99:1 dr.
我们在此报告一种新型广谱抗生素的高效、立体选择性、无需色谱分离的合成方法。该路线的特点是构建具有功能化的三肽骨架，通过 Pd 催化的 Suzuki-Miyaura 反应高产率地进行大环化，以及在后期通过最小的立体化学侵蚀用关键酰胺键进行精心设计。通过广泛的反应开发和分析理解，这些关键的进展使得可以在 17 步、总收率为 15%、>99% HPLC 和 >99:1 dr 的条件下制备 。
