Stereoselective Synthesis of 8-Oxabicyclo[3.2.1]octane-2,3,4,6,7-pentols and Total Asymmetric Synthesis of 2,6-Anhydrohepturonic Acid Derivatives and ofβ-C-manno-Pyranosides Suitable for the Construction of (1→3)-C,C-Linked Trisaccharides

Abstract

Enantiomerically pure (+)-(1S,4S,5S,6S)-6-endo-(benzyloxy)-5-exo-{[(tert-butyl)dimethylsilyl]oxy}-7-oxabicyclo[2.2.1]heptan-2-one ((+)-5) and its enantiomer (−)-5, obtained readily from the Diels-Alder addition of furan to 1-cyanovinyl acetate, can be converted with high stereoselectivity into 8-oxabicyclo[3.2.1]octane-2,3,4,6,7-pentol derivatives (see 23 – 28 in Scheme 2). A precursor of them, (1R,2S,4R,5S,6S,7R,8R)-7-endo-(benzyloxy)-8-exo-hydroxy-3,9-dioxatricyclo[4.2.1.02,4]non-5-endo-yl benzoate ((−)-19), is transformed into (1R,2R,5S, 6S,7R,8S)-6-exo,8-endo-bis(acetyloxy)-2-endo-(benzyloxy)-4-oxo-3,9-dioxabicyclo[3.3.1]non-7-endo-yl benzoate ((−)-43) (see Scheme 5). The latter is the precursor of several protected 2,6-anhydrohepturonic acid derivatives such as the diethyl dithioacetal (−)-57 of methyl 3,5-di-O-acetyl-2,6-anhydro-4-O-benzoyl-D-glycero-D-galacto-hepturonate (see Schemes 7 and 8). Hydrolysis of (−)-57 provides methyl 3,5-di-O-acetyl-2,6-anhydro-4-O-benzoyl-D-glycero-D-galacto-hepturonate 48 that undergoes highly diastereoselective Nozaki-Oshima condensation with the aluminium enolate resulting from the conjugate addition of Me2AlSPh to (1S,5S,6S,7S)-7-endo-(benzyloxy)-6-exo-{[(tert-butyl)dimethylsilyl]oxy}-8-oxabicyclo[3.2.1]oct-3-en-2-one ((−)-13) derived from (+)-5 (Scheme 12). This generates a β-C-mannopyranoside, i.e., methyl (7S)-3,5-di-O-acetyl-2,6-anhydro-4-O-benzoyl-7-C-[(1R,2S,3R,4S,5R,6S,7R)-6-endo-(benzyloxy)-7-exo-{[(tert-butyl)dimethylsilyl]oxy}-4-endo-hydroxy-2-exo-(phenylthio)-8-oxabicyclo[3.2.1]oct-3-endo-yl]-L-glycero-D-manno-heptonate ((−)-70; see Scheme 12), that is converted into the diethyl dithioacetal (−)-75 of methyl 3-O-acetyl-2,6-anhydro-4,5-dideoxy-4-C-{[methyl (7S)-3,5,7-tri-O-acetyl-2,6-anhydro-4-O-benzoyl-L-glycero-D-manno-heptonate]-7-C-yl}-5-C-(phenylsulfonyl)-L-glycero-D-galacto-hepturonate (76; see Scheme 13). Repeating the Nozaki-Oshima condensation to enone (−)-13 and the aldehyde resulting from hydrolysis of (−)-75, a (1→3)-C,C-linked trisaccharide precursor (−)-77 is obtained.