Carbasugar analogues of galactofuranosides: α-O-linked derivatives

Abstract

Using an indirect method, we have synthesised α-linked carbasugar analogues of galactofuranosides for the first time. Ring opening of a β-talo configured carbasugar 1,2-epoxide by alcohol nucleophiles under Lewis acidic conditions proceeded with very good regioselectivity to give α-talo configured C1-substituted ethers with a free OH-group at the C2 position. Inversion of configuration at C2 by an oxidation-reduction sequence gave the α-galacto configured carbahexofuranose C1 ethers. A carbadisaccharide corresponding to the Galf(α1→3)Manp substructure from Apodus deciduus galactomannan was synthesised to exemplify the method.

Keywords: carbasugars; etherification; galactofuranose; glycomimetics; pseudodisaccharides; regioselective.

Figure 1

Structures of carbapyranose and carbafuranose 1,2-epoxides.

Scheme 1

(i) Bu₂SnO, MeOH, 70 °C; (ii) BzCl, toluene, 82%; (iii) TsCl, py, 50 °C, 86%; (iv) NaOMe, MeOH, 81%.

Scheme 2

(i) ROH, BF₃^.OEt₂, CH₂Cl₂, RT; 8, 90%; 11, 57%; (ii) Ac₂O, py; 9, >99%; 12, 91%; (iii) (COCl)₂, DMSO, CH₂Cl₂, −60 °C, then Et₃N, RT; 15, 88%; 16, 68%; (iv) L-selectride, THF, 0 °C; 17, 78%; 18, 66%.

Figure 2

a) Structures of 13 and 14; b) observed NOEs consistent with structure 14; c) observed NOEs inconsistent with structure 14x.