Enantioselective Total Syntheses of Sannamycins A and B

Aminoglycoside antibiotics are one of the oldest and most clinically relevant classes of anti-infective agents, yet their complex molecular architectures have restricted access through bottom-up syntheses for decades. Herein we report enantioselective syntheses of 2-deoxyfortamine-type aminoglycosides sannamycins A and B. The described strategy involves an enantioselective dearomative hydroamination, rapid stereo- and chemoselective introduction of heteroatom functionalities, and a unique skeletal rearrangement to forge the aminocyclitol core. The carbohydrate fragment was elaborated from Cyrene, a readily available enantioenriched starting material, and was used in a stereoselective glycosylation reaction to deliver natural products in 14 and 17 steps, respectively, from benzene.