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.