Facile Synthesis of Neokotalanol, a Potent α-glycosidase Inhibitor Isolated from the Ayurvedic Traditional Medicine " Salacia"

Abstract

Neokotalanol (5) is a sulfonium-type α-glucosidase inhibitor isolated from the traditional Ayurvedic medicine "Salacia." Its potency against maltase-glucoamylase was 2000-fold stronger than acarbose. Despite 5 having been recognized as the most active among this series of sulfonium salts, a facile and effective synthetic protocol leading to 5 has not been established to date because of the difficulty in selecting and designing a protected key intermediate. In this study, an appropriately protected epoxide (β-20) was successfully designed and diastereoselectively synthesized from the easily accessible d-galactose (18). By use of β-20, S-alkylation of sulfides (7b) was successfully proceeded in a highly diastereoselective manner to afford 5 in a good total yield (11%, via 14 steps), which was superior to the three previously reported sequences (∼1% via 15 steps, ∼0.5% via 18 steps, ∼2% via 14 steps).