Studies on the transformation of nitrosugars into iminosugars III: synthesis of (2R,3R,4R,5R,6R)-2-(hydroxymethyl)azepane-3,4,5,6-tetraol and (2R,3R,4R,5R,6S)-2-(hydroxymethyl)azepane-3,4,5,6-tetraol

A divergent synthesis of the two novel polyhydroxylated azepanes (2R,3R,4R,5R,6R)-2-(hydroxymethyl)azepane-3,4,5,6-tetraol and (2R,3R,4R,5R,6S)-2-(hydroxymethyl)azepane-3,4,5,6-tetraol from d-mannose is described. The method involves a Henry reaction between dimethyl-tert-butylsilyl 2,3-O-isopropylidene-α-d-lyxo-pentodialdo-1,4-furanoside and 2-nitroethanol followed by a reductive ring closure of the resulting epimeric nitro aldols. Glycosidase inhibition tests showed that (2R,3R,4R,5R,6S)-2-(hydroxymethyl)azepane-3,4,5,6-tetraol exhibits a weak but selective inhibition against α-l-fucosides.

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1-O-t-Butyldimethylsilyl-6-deoxy-2,3-di-O-isopropyliden-6-nitro-d-glycero-α-d-manno-heptofuranoseC16H31NO8Si[α]D23=+30.6 (c 1.0, chloroform)Source of asymmetry: d-mannoseAbsolute configuration: (1R,2S,3S,4R,5R,6R)

1-O-t-Butyldimethylsilyl-6-deoxy-2,3-di-O-isopropyliden-6-nitro-l-glycero-α-d-manno-heptofuranoseC16H31NO8Si[α]D23=+3.2 (c 1.0, chloroform)Source of asymmetry: d-mannoseAbsolute configuration: (1R,2S,3S,4R,5R,6S)

6-Benzyloxycarbonylamino-1-O-t-butyldimethylsilyl-6-deoxy-2,3-di-O-isopropyliden-d-glycero-α-d-manno-heptofuranoseC24H39NO8[α]D23=+14.5 (c 0.23, chloroform)Source of asymmetry: d-glucoseAbsolute configuration: (1R,2S,3S,4R,5R,6R)

6-Benzyloxycarbonylamino-1-O-t-butyldimethylsilyl-6-deoxy-2,3-di-O-isopropyliden-d-glycero-α-d-manno-heptofuranoseC24H39NO8[α]D23=+18.1 (c 0.35, chloroform)Source of asymmetry: d-glucoseAbsolute configuration: (1R,2S,3S,4R,5R,6S)

(3aR,6R,7R,8R,8aS)-Hexahydro-6-(hydroxymethyl)-2,2-dimethyl-3aH-[1,3]dioxolo[4,5-c]azepine-7,8-diolC10H19NO5[α]D23=+6.3 (c 0.9, methanol)Source of asymmetry: d-mannoseAbsolute configuration: (3aR,6R,7R,8R,8aS)

(3aR,6S,7R,8R,8aS)-Hexahydro-6-(hydroxymethyl)-2,2-dimethyl-3aH-[1,3]dioxolo[4,5-c]azepine-7,8-diolC10H19NO5[α]D23=-1.7 (c 0.12, methanol)Source of asymmetry: d-mannoseAbsolute configuration: (3aR,6S,7R,8R,8aS)

(2R,3R,4R,5R,6R)-2-(Hydroxymethyl)azepane-3,4,5,6-tetraolC7H15NO5[α]D23=-3.6 (c 3.2, methanol/water 1:1)Source of asymmetry: d-mannoseAbsolute configuration: (2R,3R,4R,5R,6R)

(2S,3R,4R,5R,6R)-2-(Hydroxymethyl)azepane-3,4,5,6-tetraolC7H15NO5[α]D23=-59.0 (c 0.9, methanol/water 1:1)Source of asymmetry: d-mannoseAbsolute configuration: (2S,3R,4R,5R,6R)

1-O-Benzyl-6-deoxy-2,3-di-O-isopropyliden-6-nitro-d-glycero-α-d-manno-heptofuranoseC17H23NO8[α]D23=+29.0 (c 0.9, chloroform)Source of asymmetry: d-mannoseAbsolute configuration: (1S,2S,3S,4R,5R,6R)

1-O-Benzyl-6-deoxy-2,3-di-O-isopropyliden-6-nitro-l-glycero-α-d-manno-heptofuranoseC17H23NO8[α]D23=+3.2 (c 0.4, chloroform)Source of asymmetry: d-mannoseAbsolute configuration: (1S,2S,3S,4R,5R,6S)