(+)-proto-Quercitol, a natural versatile chiral building block for the synthesis of the α-glucosidase inhibitors, 5-amino-1,2,3,4-cyclohexanetetrols

Abstract

An efficient synthesis of diastereomerically pure 5-amino-1,2,3,4-cyclohexanetetrols (6 and 11) and quercitol derivatives from naturally available (+)-proto-quercitol (1) is described. The stereochemistry of 1 is perfectly set up for regioselective protection of the hydroxy group which was further functionalized into the target aminocyclitol in a straightforward manner. The present approach provides a protocol for preparing aminocyclitols in large quantities. In addition, the absolute stereochemistry of (+)-proto-quercitol was addressed using the modified Mosher's method. Of the synthesized aminocyclitols, 11 potentially inhibits α-glucosidase with an IC50value of 12.5 μM, which is 45 times greater than that of the standard antidiabetes drug, Acarbose®. © 2009 Elsevier Ltd. All rights reserved.