Total Synthesis of Complex Nucleoside Antibiotics Ezomycin A1 and A2
Zhoupeng Zhao1, Shuai Fan1,2, Shuaibo Yang1,3
1State Key Laboratory of Natural Product Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou730000, P.R. China.
Abstract:
The complex nucleoside antibiotics ezomycin A1 and A2 have stood as formidable synthetic challenges for half a century due to their density of polar functional groups and unique trans-fused bicyclic framework. Here, we disclose their long-awaited first total synthesis. This convergent and modular strategy is enabled by a stereoselective nickel-catalyzed reductive cross-coupling, a de novo asymmetric carbohydrate synthesis, and a mild (p-Tol)2SO/Tf2O-promoted N-glycosylation. This work not only establishes a unified synthetic route to the ezomycin family but also provides robust methodologies for the precise assembly of sterically demanding, highly functionalized nucleoside natural products.
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