Total Synthesis of Nikkomycin Sz and Nikkomycin Soz.

The nikkomycins Sz/Soz are a class of locked nucleoside antibiotics that share a common [5,6] trans-bicyclic core. Herein we present an efficient synthesis of these nikkomycins from diene, using neighboring group participation N-glycosylation and stereoselective oxidation state installation. This synthetic strategy overcomes several challenges due to the poor redox tolerance of the uracil base, the high strain of the trans-fused furanopyran C8 monosaccharides, and the acid-sensitive glycosidic bond when dealing with the deoxynucleotide natural product nikkomycin Sz.