AbstractThe first asymmetric total synthesis of the reported isostreptenol III 1 is accomplished in high overall yield starting from D‐ribose. Incompatible spectroscopic data of the synthetic isostreptenol III in comparison to that of the reported isolate led us to propose a revised structure 2. The structure of the isolated (3R,4S)‐isostreptenol III was revised to (3R,4R)‐isostreptenol III. The salient features of this synthesis are highly diastereoselective Wittig olefination, regioselective epoxide opening, and stereoselective installation of hydroxymethyl group dictated by the inherent cis‐stereochemistry of the acetonide group of the lactol derived from D‐ribose.