Synthesis of antimetabolites of sucrose

Abstract

The C-disaccharides D-glycero-D-ido-D-lyxo-7,11-anhydro-6-deoxydodec-5-ulofuranose-(5,2)7a and D-glycero-D-I-D-lyxo-7,11-anhydro-1-O-benzyloxysuccinyl-6-deoxydodec-5-ulofuranose(5,2)7b, antimetabolites of sucrose, the second of which is provided with a succinyl group which allows its linkage to biopolymers, have been synthesized. Hydroxymercuriation of the easily available 3-(2′, 3′, 4′, 6′-tetra-O-benzyl-α-D-glucopyranosyl)prop-1-ene 1 followed by iododemercuriation, oxidation, and treatment of the so obtained iodo ketone with triphenylphosphine afforded the stabilized ylide 3-(2′,3′,4′,6′-tetra-O-benzyl-α-D-glucopyranosyl)-2-oxopropylidene-triphenylphosphorane 2. Reaction of the ylide 2 with a properly protected D-glyceraldehyde 3 afforded the α,β-unsaturated ketone 4 with a 12-carbon-atom skeleton, the stereoselective osmylation of which, followed by deprotection, gave the C-disaccharide 7a. To obtain the succinylated C-disaccharide 7b, (S)-2-O-benzyl-3-O-(benzyloxysuccinyl)glyceraldehyde 3b was employed, which was obtained by enzymic benzyloxysuccinylation of 2-O-benzylglycerol and subsequent oxidation.