The first convergent total synthesis of penarolide sulfate A2, a novel α-glucosidase inhibitor

Penarolide sulfate A(2), a 31-membered macrolide encompassing a proline residue and three sulfate groups, was firstly synthesized in 16 linear steps with 4.8% overall yield. Three consecutive stereogenic centers in penarolide sulfate A(2) were efficiently derived from natural chiral template L-arabinose. The crucial assembly reactions included Brown asymmetric allylation, olefin cross-metathesis, alkyne-epoxide coupling, and macrolactamization. The anti-yeast alpha-glucosidase activities of penarolide sulfate A(2) and its fully desulfated derivative were examined showing IC50 values of 4.87 and 10.74 mu g mL(-1), respectively.