Synthesis of three branched iminosugars [(3R,4R,5S)-3-(hydroxymethyl)piperidine-3,4,5-triol, (3R,4R,5R)-3-(hydroxymethyl)piperidine-3,4,5-triol and (3S,4R,5R)-3-(hydroxymethyl)piperidine-3,4,5-triol] and a branched trihydroxynipecotic acid [(3R,4R,5R)-3,4

Homochiral piperidines containing a quaternary carbon branch at C-2 of the piperidine ring may be made from readily available carbohydrate lactones containing a branched 2-C-hydroxymethyl substituent. This gives an easy access to the branched iminosugars. In particular a trihydroxypipecolic acid analogue, (3R,4R,5R)-3,4,5-trihydroxypiperidine-3-carboxylic acid, has been synthesised efficiently from the starting material d-ribose and (3S,4R,5S)-3-(hydroxymethyl)piperidine-3,4,5-triol was found to be a specific inhibitor of α-d-glucosidase from Bacillus Stearothermophilus with an IC50 value of 93 μM.

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5-Amino-5-deoxy-2-C-hydroxymethyl-2,3-O-isopropylidene-l-lyxono-1,5-lactamC9H15NO5[α]D21=-14.0 (c 0.18, MeOH)Source of chirality: 2,3-O-isopropylidene-l-lyxono-1,4-lactoneAbsolute configuration: (2R,3R,4S)

Amino-5-deoxy-2-C-hydroxymethyl-l-lyxono-1,5-lactamC6H11NO5[α]D21=+44.0 (c 0.42, H2O)Source of chirality: 2,3-O-isopropylidene-l-lyxono-1,4-lactoneAbsolute configuration: (2R,3R,4S)

1,5-Dideoxy-2-C-hydroxymethyl-1,5-imino-l-lyxitolC6H13NO4[α]D21=+7.2 (c 0.92, H2O)Source of chirality: 2,3-O-isopropylidene-l-lyxono-1,4-lactoneAbsolute configuration: (2R,3R,4S)

5-Amino-5-deoxy-2-C-hydroxymethyl-2,3-O-isopropylidene-d-ribono-1,5-lactamC9H15NO5[α]D28-66.0 (c 0.15, MeOH)Source of chirality: d-riboseAbsolute configuration: (2R,3R,4R)

1,5-Dideoxy-2-C-hydroxymethyl-1,5-imino-d-ribitolC6H13NO4[α]D25=-3.7 (c 0.49, H2O)Source of chirality: d-riboseAbsolute configuration: (2R,3R,4R)

5-Amino-5-deoxy-2-C-hydroxymethyl-d-ribono-1,5-lactamC6H11NO5[α]D23=-2.3 (c 0.37, H2O)Source of chirality: d-riboseAbsolute configuration: (2R,3R,4R)

3,3-Dimethyl-2,4,11-trioxa-8-aza-tricyclo[4.3.2.01,5]undecan-10-oneC9H13NO4[α]D22=-82.6 (c 0.36, EtOAc)Source of chirality: d-riboseAbsolute configuration: (1R,5R,6R)

1,5-Dideoxy-2-C-hydroxymethyl-1,5-imino-d-arabinitolC6H13NO4[α]D21=-5.0 (c 0.28, H2O)Source of chirality: d-riboseAbsolute configuration: (2S,3R,4R)

2-C-Carboxylic acid-1,5-dideoxy-1,5-imino-d-arabinitolC6H11NO5[α]D23=-19.4 (c 0.21, H2O)Source of chirality: d-riboseAbsolute configuration: (2R,3R,4R)