A novel methodology for the stereospecific synthesis of C- glycosides is proposed. This methodology is based on the preliminary attachment of a substituent containing a latent carbon-nucleophilic function to one of the hydroxyl function of a cyclic sugar derivative, followed by the creation of a carbon- carbon bond between this group and the anomeric center of the sugar. Thus, O-benzylated, N-benzylated and O-phenylated sugars should lead to """"""""internal"""""""" C-glycosides (isochromans, tetrahydroisoquinolines and 2,3-dihydrobenzofurans resp.) which could be cleaved to C-glycosylated benzene derivatives or further elaborated (for example into tetrahydroisoquinoline alkaloids). The one-step transfer of a C-nucleophile might be achieved using a difunctional silyl derivative as a temporary linkage to the sugar- hydroxyl function: thus O-aryloxysilyl, as well as O-aryl-and O- allyl-dimethylsilyl carbohydrate derivatives are expected to undergo intra-molecular C-glycosidation with simultaneous cleavage of the auxiliary linkage upon treatment with a Lewis acid, thereby providing a highly efficient and general method of stereospecific C-glycosidation. This methodology will be used for the synthesis of a number of biologically and pharmacologically significant structures. Thus a series of arabino nucleoside analogs, in particular the dideaza analog of ara-C, one of the most potent agents against acute leukemia, benzenoid analogs of cyclouridine and cyclocytidine, as well indole C-nucleosides related to the antiviral agent are-A will be prepared by the intramolecular C-glycosylation of suitably substituted benzene and indole derivatives. The proposed methodology provides also a short approach to natural internal C- glycosides such as bergenin and related compounds, as well as to C-glycosyl flavonoids. Furthermore, N-benzylated amino sugars are precursors of chiral tetrahydroisoquinolines which have an extremely interesting substitution pattern because of its relation to that of tetra-hydroisoquinolines derived from biogenic amines and certain psychopharmacological drugs. C-benzylation of the corresponding N-benzylidene imino sugars, expected to be highly stereoselective, gives an intermediate which should lead in one step, by a """"""""double intramolecular C-arylation"""""""" process, to the skeleton of the isopavine alkaloids. These reactions provide a short synthetic route from carbohydrates to chiral tetra- hydroisoquinoline alkaloids.
| Martin, O R; Hendricks, C A; Deshpande, P P et al. (1990) Synthesis of C-glycosylarenes by way of internal reactions of benzylated and benzoylated carbohydrate derivatives. Carbohydr Res 196:41-58 |
| Martin, O R; Rao, S P; Hendricks, C A et al. (1990) Multiple and long-range participation of benzyl groups in intramolecular C-arylation reactions of benzylated glycosides. Carbohydr Res 202:49-66 |
