The allyl ether as a protecting group in carbohydrate chemistry. Part IX. Synthesis of derivatives of 1,6-anhydro-β-D-galactopyranose

Abstract

1,6-Anhydro-2,3-di-O-benzyl-β-D-galactopyranose was prepared by four different methods and isolated and characterised as the crystalline p-nitrobenzoate. (a) Allylation of 1,6-anhydro-2-O-benzyl-β-D-galactopyranose gave a mixture of di- and mono-allyl derivatives. The mono-allyl derivatives were benzylated and the allyl group was removed. (b) Phenyl 4-O-allyl-2,3-di-O-(but-2-enyl)-β-D-galactopyranoside was treated with potassium t-butoxide in dimethyl sulphoxide, which removed the but-2-enyl groups, isomerised the allyl group, and converted the phenyl 4-O-(prop-1-enyl)-β-D-galactopyranoside formed into 1,6-anhydro-4-O-(prop-1-enyl)-β-D-galactopyranose. Benzyl chloride was then added to the solution to give the 2,3-di-O-benzyl derivative and the prop-1-enyl group was subsequently hydrolysed. (c) 1,6:2,3-Dianhydro-β-D-talopyranose was converted into the 4-O-allyl derivative, which was hydrolysed with base to give 4-O-allyl-1,6-anhydro-β-D-galactopyranose. This was benzylated and the allyl group was removed. (d) Tritylation of 1,6-anhydro-2-O-benzyl-β-D-galactopyranose gave predominantly 1,6-anhydro-2-O-benzyl-4-O-trityl-β-D-galactopyranose, which was benzylated and the trityl group was removed. The 1,6-anhydro-2,3-di-O-benzyl-β-D-galactopyranose was condensed with 2,3,4-tri-O-benzyl-6-O-(but-2-enyl)-D-galactopyranosyl chloride, under conditions shown previously to give predominantly 1,2-cis-glycosidic linkages, to give a disaccharide derivative which was converted into crystalline 1,2,3,6-tetra-O-acetyl-4-O-(2,3,4,6-tetra-O-acetyl-α-D-galactopyranosyl)-α-D-galactopyranose. 1,6-Anhydro-2-O-benzyl-4-O-trityl-β-D-galactopyranose was converted into crystalline 3-O-allyl-1,6-anhydro-2-O-benzyl-4-O-trityl-β-D-galactopyranose, an intermediate for the synthesis of 1,6-anhydro-2,4-di-O-benzyl-β-D-galactopyranose. 1,6:2,3-Dianhydro-4-O-benzyl-β-D-talopyranose was converted into 1,6-anhydro-2-azido-4-O-benzyl-2-deoxy-β-D-galactopyranose, which was isolated and characterised as the crystalline p-nitrobenzoate. Preliminary investigations on the conversion of 1,6-anhydro-2,3-di-O-benzyl-4-O-p-nitrobenzoyl-β-D-galactopyranose into 6-O-acetyl-2,3-di-O-benzyl-4-O-p-nitrobenzoyl-D-galactopyranosyl chloride by the action of acetyl chloride in the presence of hydrogen chloride (‘chloracetolysis’) and on the reaction of N-bromosuccinimide with 6-O-allyl-1,2:3,4-di-O-isopropylidene-α-D-galactopyranose are also reported.