First stereoselective total synthesis and stereochemical revision of Vittarilide-B using a carbohydrate-based strategy

Abstract

The first stereoselective total synthesis of Vittarilide-B and its revised structure have been successfully accomplished. The synthesis began with D-glucal as the starting material, which was transformed into the reported structure of Vittarilide-B. Although the ¹H NMR, ¹³C NMR, and NOE data for the synthesized compound corresponded to the naturally isolated structure, the optical rotation was inconsistent. This discrepancy necessitated the synthesis of the enantiomer using l-rhamnose as the starting material, which yielded an optical rotation consistent with that of the isolated compound. The synthesis involved the preparation of 5-deoxy-D-arabinono-1,4-lactone via RuO₄-catalyzed oxidative cleavage of 6-deoxyglucal diacetate derived from D-glucal, followed by alkaline hydrolysis. The lactone was then protected with TBS, esterified with TBS-protected caffeic acid, and deprotected to afford Vittarilide-B. This synthesis not only confirmed the structure of Vittarilide-B but also resulted in the stereochemistry revision of the natural product. The revised structure was synthesized using a product whose spectral data precisely matched the reported data of Vittarilide-B, representing a noteworthy contribution to the Vittarilide family of compounds. This concise synthetic approach provides access to Vittarilide-B its stereoisomer, enabling further investigation of their biological activities.