Green syntheses of new 2-C-methyl aldohexoses and 5-C-methyl ketohexoses: d-tagatose-3-epimerase (DTE)—a promiscuous enzyme

The Kiliani synthesis on the 4 readily accessible ketohexoses (d-fructose, d-tagatose, l-sorbose, d-psicose) allows access to 4 diastereomeric 2-C-methyl-aldohexoses (2-C-methyl-d-mannose, 2-C-methyl-d-talose, 2-C-methyl-l-gulose, 2-C-methyl-d-allose) and 4 diastereomeric 2-C-methyl-alditols (2-C-methyl-d-mannitol, 2-C-methyl-d-talitol, 2-C-methyl-l-gulitol, 2-C-methyl-d-allitol). Microbial oxidation of 2-C-methyl-d-mannitol and 2-C-methyl-l-gulitol gave 5-C-methyl-d-fructose; microbial oxidation of 2-C-methyl-d-talitol afforded 5-C-methyl-d-psicose, whereas 2-C-methyl-d-allitol formed 5-C-methyl-l-psicose. Both enantiomers of 5-C-methyl-fructose were equilibrated by d-tagatose-3-epimerase (DTE) with both enantiomers of 5-C-methyl-psicose. These transformations demonstrate that polyol dehydrogenases and DTE act on branched synthetic sugars. Full NMR analyses show that 5-C-methyl-d-fructose is present as the β-pyranose and β-furanose forms in a ratio of 90:10; all pyranose and furanose forms of 5-C-methyl-d-psicose are present in solution. The combination of chemical and biological procedures allows the environmentally friendly generation of a new family of branched monosaccharides.

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2,3:5,6-Di-O-isopropylidene-2-C-iodomethyl-d-mannono-1,4-lactoneC13H19IO6Ee = 100%[α]D22=+31.8 (c 1.09, CHCl3)Source of chirality: d-fructose as starting material

2,3:5,6-Di-O-isopropylidene-2-C-methyl-d-mannitolC13H24O6Ee = 100%[α]D22=-2.8 (c 1.02, CHCl3)Source of chirality: d-fructose as starting material

2-C-Methyl-d-mannitolC7H16O6Ee = 100%[α]D21=-8.0 (c 1.02, MeOH)Source of chirality: d-fructose as starting material

2-C-Methyl-d-talitolC7H16O6Ee = 100%[α]D21=-17.2 (c 1.0, water)Source of chirality: d-tagatose as starting material

2,3:5,6-Di-O-isopropylidene-2-C-methyl-d-talofuranoseC13H22O6Ee = 100%[α]D22=-15.2 (c 1.0, CHCl3)Source of chirality: d-tagatose as starting material

2-C-Methyl-d-taloseC7H14O6Ee = 100%[α]D22=+11.8 (c 2.0, water)Source of chirality: d-tagatose as starting material

2,3:5,6-Di-O-isopropylidene-2-C-iodomethyl-l-gulono-1,4-lactoneC13H19IO6Ee = 100%[α]D24=+27.8 (c 1.07, CHCl3)Source of chirality: l-sorbose as starting material

2,3:5,6-Di-O-isopropylidene-2-C-methyl-l-gulono-1,4-lactoneC13H20O6Ee = 100%[α]D24=+59.0 (c 1.09, CHCl3)Source of chirality: l-sorbose as starting material

2,3:5,6-Di-O-isopropylidene-2-C-methyl-l-gulitolC13H24O6Ee = 100%[α]D22=-7.3 (c 1.52, CHCl3)Source of chirality: l-sorbose as starting material

2-C-Methyl-l-gulitolC7H16O6Ee = 100%[α]D22=-9.7 (c 0.76, water)Source of chirality: l-sorbose as starting material

2,3:5,6-Di-O-isopropylidene-2-C-methyl-l-gulofuranoseC13H22O6Ee = 100%[α]D22=-1.0 (c 1.32, CHCl3)Source of chirality: l-sorbose as starting material

2-C-Methyl-l-guloseC7H14O6Ee = 100%[α]D22=+12.0 (c 1.0, water)Source of chirality: l-sorbose as starting material

2,3:5,6-Di-O-isopropylidene-2-C-iodomethyl-d-talono-1,4-lactoneC13H19IO6Ee=100%[α]D22=-44.5 (c 1.0, CHCl3)Source of chirality: d-tagatose as starting material

2,3:5,6-Di-O-isopropylidene-2-C-methyl-d-talono-1,4-lactoneC13H20O6Ee = 100%[α]D22=+15.1 (c 1.0, CHCl3)Source of chirality: d-tagatose as starting material

2,3:5,6-Di-O-isopropylidene-2-C-methyl-d-talitolC13H24O6Ee = 100%[α]D22=+11.1 (c 1.0, CHCl3)Source of chirality: d-tagatose as starting material

2,3:5,6-Di-O-isopropylidene-2-C-iodomethyl-d-allono-1,4-lactoneC13H19IO6Ee = 100%[α]D22=+32.3 (c 1.0, CHCl3)Source of chirality: d-psicose as starting material

2,3:5,6-Di-O-isopropylidene-2-C-methyl-d-allono-1,4-lactoneC13H20O6Ee = 100%[α]D20=-50.0 (c 1.02, CHCl3)Source of chirality: d-psicose as starting material

2,3:5,6-Di-O-isopropylidene-2-C-methyl-d-allitolC13H24O6Ee = 100%[α]D25=+7.7 (c 1.0, CHCl3)Source of chirality: d-psicose as starting material

2-C-Methyl-d-allitolC7H16O6Ee = 100%[α]D25=+12.5 (c 0.99, MeOH)Source of chirality: d-psicose as starting material

2,3:5,6-Di-O-isopropylidene-2-C-methyl-d-allofuranoseC13H22O6Ee = 100%[α]D22=-1.0 (c 1.0, CHCl3)Source of chirality: d-psicose as starting material

2-C-Methyl-d-alloseC7H14O6Ee = 100%[α]D22=-3.5 (c 1.0, water)Source of chirality: d-psicose as starting material

5-C-Methyl-d-psicoseC7H14O6Ee = 100%[α]D20=-25.2 (c 1.0, water)Source of chirality: d-tagatose as starting material

5-C-Methyl-l-psicoseC7H14O6Ee = 100%[α]D20=+24.5 (c 1.0, water)Source of chirality: d-psicose as starting material

5-C-Methyl-d-fructoseC7H14O6Ee = 100%[α]D25=-85.8 (c 1.0, water) from d-fructose[α]D25=-85.2 (c 1.0, water) from l-sorbose

5-C-Methyl-l-fructoseC7H14O6Ee = 100%[α]D20=+83.2 (c 1.0, water)Source of chirality: d-psicose as starting material