Catalytic asymmetric synthesis of stereoisomers of 1-C-n-butyl-LABs for the SAR study of α-glucosidase inhibition

Abstract

We achieved synthesis of seven stereoisomers of 1-C-n-butyl-L-iminofuranose derivatives using catalytic asymmetric alkylation and Negishi coupling as key reactions. The synthetic strategy based on these key reactions was quite useful, since both α- and β-iminofuranoses could be obtained by switching the chirality of the ligand employed for the AAA reaction. The common intermediates for α- and β-isomers were subjected to further manipulations to install a diol unit at C2 and C3 to give the desired stereoisomers of L-iminofuranose derivatives. We achieved the preparation of all stereoisomers of 1-C-n-butyl-L-iminofuranose derivatives, with the exception of β-lyxo type iminofuranose. It is noteworthy that a synthetic route for many stereoisomers of iminofuranose derivatives was developed. Unfortunately, none of the L-iminofuranoses obtained showed inhibitory activity against the α-glycosidases examined—e.g., maltase, sucrase, and isomaltase.