β-Acarbose. IV. Model Studies on the Alkylation of Cyclohexylamine with a Carbohydrate Epoxide

Abstract

1,6:3,4-Dianhydro-2-O-benzyl-β-D-galactose has been treated with cyclohexylamine to give an amino alcohol, convertible into 2,3-di-O-acetyl-1,6-anhydro-4-cyclohexylamino-4-deoxy-β-D-glucose by reduction and acetylation. The anhydro bridge of this diacetate has been successfully opened under acetolysis conditions. The original amino alcohol has also been converted into a cyclic carbamate, a carbamate and an aziridine, by utilizing a variety of reagents and conditions. The 1,6-anhydro bridge of the cyclic carbamate, also containing a 2-O-benzyl ether, could be opened under acetolysis conditions but a comparable reaction was best done on the derived 2-O-acetyl compound. The resulting mixture of D-glucosyl acetates, still containing a cyclic carbamate, was convered into a methyl β-D-glucoside. The cyclic carbamate could be removed by hydrolysis with aqueous base to give a model glycoside for a synthesis of β-acarbose. Single-crystal X-ray structure determinations are reported for 2,3-di-O-acetyl-4-[acetyl(cyclohexyl)amino]-1,6-anhydro-4-deoxy-β-D-glucose, 1,6-anhydro-2-O-benzyl-3,4-[N-(cyclohexyl)epimino]-3,4-dideoxy-β-D-allose and methyl 2,6-di-O-acetyl-3,4-O,N-carbonyl-4-cyclohexylamino-4-deoxy-β-D-glucoside.