Stereoselective enzymatic synthesis of monoglucosyl-myo-inositols with in vivo anti-inflammatory activity

The monoglucosyl-inositols α-d-glucopyranosyl-(1→4)-4d-myo-inositol 3 and α-d-glucopyranosyl-(1→1)-1d-myo-inositol 4 were synthesized by a combined enzymatic transglucosylation and hydrolysis strategy, using cyclodextrin glucosyl transferase (CGTase) from Thermoanaerobacter sp., followed by hydrolysis with Aspergillus niger glucoamylase. The glucosides were separated by preparative HPLC and fully characterized by extensive 1D and 2D NMR studies. The structure of the regioisomer 4 was confirmed by X-ray crystallography of its perbenzoylated derivative 4a. Both isomers demonstrated in vivo anti-inflammatory activity at comparative levels to corticosterone on mouse ear oedema induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) and in rat hind paw oedema induced by carrageenan.

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α-d-Glucopyranosyl-(1→1)-1d-myo-inositolC12H22O11[α]D20=+85.8 (c 0.1, H2O)Source of chirality: cyclodextrin glucosyl transferase from Thermoanaerobacter sp.Absolute configuration: (1S,2R,3S,4S,5R,1S,2R,3S,4S,5R)

α-d-Glucopyranosyl-(1→4)-4d-myo-inositolC12H22O11[α]D20=+66.5 (c 0.1, H2O)Source of chirality: cyclodextrin glucosyl transferase from Thermoanaerobacter sp.Absolute configuration: (1S,2R,3R,4S,5S,1S,2R,3S,4S,5R)

α-d-(2,3,4,6-Tetra-O-benzoyl)-glucopyranosyl-(1→4)-4d-(1,2,3,5,6-penta-O-benzoyl)-myo-inositolC75H58O20[α]D20=+72.95 (c 1.05, CHCl3)Source of chirality: α-d-glucopyranosyl-(1→4)-4d-myo-inositolAbsolute configuration: (1S,2R,3R,4S,5S,1S,2R,3S,4S,5R)

α-d-(2,3,4,6-Tetra-O-benzoyl)-glucopyranosyl-(1→1)-1d-(2,3,4,5,6-penta-O-benzoyl)-myo-inositolC75H58O20[α]D20=+30.5 (c 2.58, CHCl3)Source of chirality: α-d-glucopyranosyl-(1→1)-1d-myo-inositolAbsolute configuration: (1S,2R,3S,4S,5R,1S,2R,3S,4S,5R)