Synthesis of a terminal A-B-C disaccharide fragment of flambamycin, curamycin, and avilamycin

Abstract

Methyl 2,6-dideoxy-4- O-[2,6-dideoxy-4- O-(3,5-dichloro-4-hydroxy-2-methoxy-6-methylbenzoyl)-β- d- arabino-hexopyranosyl]-α d- arabino- hexopyranoside ( 25) corresponds to an A-B-C disaccharide subunit of the title antibiotics. It was synthesized from suitably protected monosaccharide and aromatic precursors. The readily available 4,6- O-benzylidene-1,2- O-( R)-propylidene-α- d-glucopyranose was converted in six steps into 2- O-acetyl-4- O-benzoyl-3- O-benzyl-6-deoxy-α d-glucopyranosyl bromide, which was condensed with methyl 3- O-benzyl-2,6-dideoxy-α- d- arabino-hexopyranoside in the presence of mercury(II) cyanide. Methyl 4- O-(2- O-acetyl-4- O-benzoyl-3- O-benzyl-6-deoxy-β- d-glucopyranosyl)-3- O-benzyl-2,6-dideoxy-α- d- arabino- hexopyranoside was converted either into methyl 2,6-dideoxy-4- O-(6-deoxy-β- d-glucopyranosyl)-α- d- arabino-hexopyranoside by removal of the protective groups or into methyl 3- O-benzyl-4- O-(3- O-benzyl-2,6-dideoxy-β- d- arabino-hexopyranosyl)-2,6-dideoxy-α- d- arabino-hexopyranoside ( 22) by selective deacetylation, Barton deoxygenation, and Zemplén debenzoylation. Disaccharide 22 was deprotonated with butylithium and treated with 4-benzyloxy-3,5-dichloro-2-methoxy-6-methylbenzoyl chloride to give the title compound 25 after hydrogenolysis.