Total synthesis of d-fagomine and 6-deoxyfagomine

Abstract

Total synthesis of d-fagomine and 6-deoxyfagomine from readily available d-lyxose is described. The key steps included regioselective and diastereoselective amination, hydroboration–oxidation, and Appel reaction. The reaction of 3,4-anti-tribenzyl ether with chlorosulfonyl isocyanate in toluene at 0 °C afforded 3,4-anti-amino alcohol, an essential compound for the preparation of d-fagomine and 6-deoxyfagomine, with a high diastereoselectivity (dr=26:1) in 74% yield. The origin of diastereoselectivity can be explained by the neighboring group effect, which leads to retention of the stereochemistry.