A precursor to the β-pyranosides of 3-amino-3,6-dideoxy- d-mannose (mycosamine)

Abstract

S N2-type reaction of 3- O-(1-imidazyl)sulfonyl-1,2:5,6-di- O-isopropylidene-α- d-glucofuranose with benzoate gave the 3- O-benzoyl-α- d- allo derivative 2, which was hydrolysed to give the 5,6-diol 3. Compound 3 was converted into the 6-deoxy-6-iodo derivative 4 which was reduced with tributylstannane, and then position 5 was protected by benzyloxymethylation, to give 3- O-benzoyl-5- O-benzyloxymethyl-6-deoxy-1,2- O-isopropylidene-α- d-allofuranose ( 6. Debenzoylation of 6 gave 7, (1-imidazyl)sulfonylation gave 8, and azide displacement gave 3-azido-5- O-benzyloxymethyl-3,6-dideoxy-1,2- O-isopropylidene-α- d-glucofuranose ( 9, 85%). Acetolysis of 9 gave 1,2,4-tri- O-acetyl-3-azido-3,6-dideoxy-α,β- d-glucopyranose ( 10 and 11). Selective hydrolysis of AcO-1 in the mixture of 10 and 11 with hydrazine acetate (→ 12), followed by conversion into the pyranosyl chloride 13, treatment with N,N-dimethylformamide dimethyl acetal in the presence of tetrabutylammonium bromide, and benzylation gave 3-azido-4- O-benzyl-3,6-dideoxy-1,2- O-(1-methoxyethylidene)-α- d-glucopyranose ( 15). Treatment of 15 with dry acetic acid gave 1,2-di- O-acetyl-3-azido-4- O-benzyl-3,6-dideoxy-β- d-glucopyranose ( 16, 86% yield) that was an excellent glycosyl donor in the presence of trimethylsilyl triflate, allowing the synthesis of cyclohexyl 2- O-acetyl-3-azido-4- O-benzyl-3,6-dideoxy-β- d-glucopyranoside ( 17, 90%). O-Deacetylation of 17, conversion of the product into the (1-imidazyl)sulfonic ester, and S N2 substitution with benzoate gave cyclohexyl 3-azido-2- O-benzoyl-4- O-benzyl-3,6-dideoxy-β- d-mannopyranoside ( 18), which was reduced and N-acetylated to give cyclohexyl 3-acetamido-2- O-benzoyl-4- O-benzyl-3,6-dideoxy-β- d-mannopyranoside ( 19).