Total Synthesis of Nikkomycin S z and Nikkomycin So z .

The nikkomycins S _z /So _z 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 S _z .