Synthesis of 6′-Aminohexyl 2-Acetamido-2-deoxy-D-galactoside Isomers and a Unique Isomerization Catalyzed by Ion Exchange Resin

Abstract

The 6-aminohexyl α- and β-pyranosides and β-furanoside of 2-acetamido-2-deoxy-D-galactose (N-acetyl-D-galactosamine) were prepared. N-Acetyl-D-galactosamine was reacted with acetyl chloride in the cold. The per-O-acetyl 1-chloro derivative was then reacted with 6-(N-trifluoroacetyl) aminohexanol in the presence of mercuric cyanide. Glycoside products were isolated by gel chroraatography, de-O-acetylated, and de-N-trifluoroacety-lated. The β-pyranoside, which is the major product, was obtained in 29% overall yield, as well as the β-furanoside. The α-pyranoside was prepared in 70% overall yield by reacting 2-acetamido-1, 3, 4, 6-tetra-O-acetyl-2-deoxy-α-D-galacto-pyranose, which is a byproduct of the above synthetic scheme (22%), with 6-(N-trifluoroacetyl)aminohexanol in the presence of boron trifluoride etherate. A strong cation exchange resin (Dowex 50X8, H⁺ form) catalyzed interconversion of the β-furanoside and the β-pyranoside, with the latter predominating at equilibrium. The α-pyranoside was not produced in any appreciable amount in the Dowex-catalyzed isomerization. Although the allyl β-pyranoside and β-furanoside of N-acetyl-D-galactosamine also isomerized under similar conditions, the competing hydrolysis of the glycosidic bond occurred to a greater extent. A possible mechanizm for the isomerization is discussed.