Stereocontrolled Synthesis of Arylomycin-Based Gram-Negative Antibiotic GDC-5338

作者：Nicholas Wong, Filip Petronijević, Allen Y. Hong, Xin Linghu, Sean M. Kelly, Haiyun Hou, Theresa Cravillion, Ngiap‐Kie Lim, Sarah J. Robinson, Chong Han, Carmela Molinaro, C. Gregory Sowell, Francis Gosselin · 发表于：Organic Letters · 年份：2019 · DOI：10.1021/acs.orglett.9b03481 · 被引用次数：21 · 研究领域：Chemical Synthesis and Analysis、Microbial Natural Products and Biosynthesis、Synthetic Organic Chemistry Methods

We report herein an efficient, stereocontrolled, and chromatography-free synthesis of the novel broad spectrum antibiotic GDC-5338 . 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 GDC-5338 in 17 steps, 15% overall yield, >99 A % HPLC, and >99:1 dr.