SYNTHESIS OF C-GLYCOSYLARENES BY WAY OF INTERNAL REACTIONS OF BENZYLATED AND BENZOYLATED CARBOHYDRATE-DERIVATIVES

"Internal" C-glycosylarenes [e.g., (2R,3S,3aS,9bR)-3,3a,5,9b-tetrahydro-3-methoxy- and -3,7-dimethoxy-2-methoxymethyl-2H-furo[3,2-c][2]benzopyran] were prepared by intramolecular reactions of 2-O-benzyl derivatives of methyl 3,5-di-O-methyl-d-xylofuranoside (2) and their conversion into authentic C-glycosylated aromatic systems was investigated. The auxiliary benzylic linkage could not be cleaved by hydrogenolysis; isochroman derivatives {e.g., (3S)-3,4-dihydro-3-[(1R,2R)-2-hydroxy-1,3-dimethoxypropyl]-5- methoxy-1H-2-benzopyran} were obtained under these conditions. However, oxidation of the primary benzylic position with ruthenium tetraoxide gave the corresponding lactone {a dihydroisocoumarin derivative, e.g., (2R,3S,3aS,9bR)-2,3,3a,9b-tetrahydro-3,7-dimethoxy-2-methoxy-methyl-5H-furo[3,2-c][2]benzopyran-5- one} which could be opened by saponification, thereby leading to a stereochemically unique C-glycosylbenzoic acid derivative. The same type of lactone was obtained directly from a derivative of 2 bearing a sufficiently reactive benzoyl group at O-2 (3,5-dimethoxybenzoyl); this process provides a useful approach to a heterocyclic system present in a variety of natural products. In related studies, the 2-O-phenyl substituent was found to be much less reactive than the 2-O-benzyl group in intramolecular Friedel-Crafts reactions of 2-O-substituted glycofuranosides. The first examples of successful internal C-arylation in the pyranoid series were achieved from 2-O-(3-methoxybenzyl)-d-mannopyranosides; the resulting "internal C-glycosides" {(2R,3S,4S,4aS,10bS)-2,3,4,4a,6,10b-hexahydro-3,4,8-trimethoxy-2-methoxymethylpyrano [3,2-c][2]benzopyran and 3,4-bis(benzyloxy)-2-benzyloxymethyl-8-methoxy analog} contain a heterocyclic skeleton closely related to that of the natural product bergenin. © 1990.