Chemoenzymatic synthesis of glycosyl-deoxyinositol derivatives. First example of a fagopyritol β-analogue containing an aminoinositol unit

The first synthesis of two fagopyritol β-analogues (β-d-galactopyranosyl-(1′→1)-conduramine F-4 and β-d-galactopyranosyl-(1′→3)-4-aminodeoxy-l-chiro-inositol) has been accomplished by a chemoenzymatic route in satisfactory yields. The key step of the synthesis is the TMSOTf-promoted glycosylation reaction of a deoxyconduritol derivative. The methodology is amenable to scale-up and expandable to the preparation of other pseudofagopyritols.

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(1R,2S,5R,6R)-2′,3′,4′,6′-Tetra-O-acetyl-β-d-galactopyranosyl-(1′,1)-2-azido-5,6-O-isopropylidenedioxycyclohex-3-eneC23H31N3O12Ee >98%[α]D20=+20 (c 0.84, CHCl3)Source of chirality: enzymatic catalysisAbsolute configuration: (1R,2S,5R,6R)

(1R,2S,5R,6R)-β-d-Galactopyranosyl-(1′,1)-2-azido-5,6-O-isopropylidenedioxycyclohex-3-eneC15H23N3O8Ee >98%[α]D20=+11 (c 0.40, MeOH)Source of chirality: enzymatic catalysisAbsolute configuration: (1R,2S,5R,6R)

(1S,2R,3R,6S)-β-d-Galactopyranosyl-(1′,1)-6-amino-5,6-cyclohex-4-ene-2,3-diolC12H21NO8Ee >98%[α]D20=-12 (c 0.26, H2O)Source of chirality: enzymatic catalysisAbsolute configuration: (1S,2R,3R,6S)

(1S,2S,3S,4R,5S,6R)-2′,3′,4′,6′-Tetra-O-acetyl-β-d-galactopyranosyl-(1′,4)-3-azido-5,6-O-isopropylidenedioxycyclohexan-1,2-diolC23H33N3O14Ee >98%[α]D20=-57 (c 0.25, CH2Cl2)Source of chirality: enzymatic catalysisAbsolute configuration: (1S,2S,3S,4R,5S,6R)

(1R,2R,3S,4S,5R,6R)-β-d-Galactopyranosyl-(1′,3)-4-aminodeoxy-l-chiro-inositolC12H23NO10Ee >98%[α]D20=+12 (c 0.48, H2O)Source of chirality: enzymatic catalysisAbsolute configuration: (1R,2R,3S,4S,5R,6R)