Synthesis, structural, and biological studies on a pseudodisaccharide containing a bicyclic, bridged carba-sugar

Two carba-sugar containing pseudodisaccharide diastereomers have been synthesized from a racemic bicyclooctene derivative. The determination of the absolute configurations was carried out by means of CD measurements, CD calculations and X-ray diffraction. The compounds showed moderate competitive inhibitory effects on chondroitin AC-I lyase.

Figure optionsDownload as PowerPoint slide

(1R,2R,3R,4R,5R,7R)-7-Benzyloxy-4,5-dihydroxy-5-methoxy-2-methoxycarbonyl-6-oxo-4,5-O-diphenylmethylidenebicyclo[2.2.2]octan-3-yl 2′-acetamido-3′,4′,6′-tri-O-acetyl-2′-deoxy-1′-thio-β-d-glucopyranosideC45H49NO15S[α]D23=-36.0 (c 0.10, CH2Cl2)Absolute configuration: (1R,2R,3R,4R,5R,7R,1′S,2′R,3′R,4′S,5′R)Source of chirality: d-glucosamine

(1S,2S,3S,4S,5S,7S)-7-Benzyloxy-4,5-dihydroxy-5-methoxy-2-methoxycarbonyl-6-oxo-4,5-O-diphenylmethylidenebicyclo[2.2.2]octan-3-yl 2′-acetamido-3′,4′,6′-tri-O-acetyl-2′-deoxy-1′-thio-β-d-glucopyranosideC45H49NO15S[α]D23=+8.3 (c 0.10, CH2Cl2)Absolute configuration: (1S,2S,3S,4S,5S,7S,1′S,2′R,3′R,4′S,5′R)Source of chirality: d-glucosamine

(1R,2R,3R,4R,5S,6R,7R)-7-Benzyloxy-4,5,6-trihydroxy-5-methoxy-2-methoxy-carbonyl-4,5-O-diphenylmethylidenebicyclo[2.2.2]octan-3-yl 2′-acetamido-3′,4′,6′-tri-O-acetyl-2′-deoxy-1′-thio-β-d-glucopyranosideC45H51NO15S[α]D23=-26.9 (c 0.13, CH2Cl2)Absolute configuration: (1R,2R,3R,4R,5S,6R,7R,1′S,2′R,3′R,4′S,5′R)Source of chirality: d-glucosamine

(1R,2R,3R,4R,5S,6R,7R)-4,5,6,7-Tetrahydroxy-5-methoxy-2-methoxycarbonyl-4,5-O-diphenylmethylidenebicyclo[2.2.2]octan-3-yl 2′-acetamido-3′,4′,6′-tri-O-acetyl-2′-deoxy-1′-thio-β-d-glucopyranosideC38H45NO15S[α]D23=-18.1 (c 0.24, CH2Cl2)Absolute configuration: (1R,2R,3R,4R,5S,6R,7R,1′S,2′R,3′R,4′S,5′R)Source of chirality: d-glucosamine

(1R,2R,3R,4R,5R,7R)-7-Benzyloxy-4,5-dihydroxy-5-methoxy-2-methoxycarbonyl-6-oxo-4,5-O-diphenylmethylidenebicyclo[2.2.2]octan-3-yl 2′-acetamido-2′-deoxy-1′-thio-β-d-glucopyranosideC39H43NO12S[α]D23=-52.6 (c 0.31, CH2Cl2)Absolute configuration: (1R,2R,3R,4R,5R,7R,1′S,2′R,3′R,4′S,5′R)Source of chirality: d-glucosamine

(1S,2S,3S,4S,5S,7S)-7-Benzyloxy-4,5-dihydroxy-5-methoxy-2-methoxycarbonyl-6-oxo-4,5-O-diphenylmethylidenebicyclo[2.2.2]octan-3-yl 2′-acetamido-2′-deoxy-1′-thio-β-d-glucopyranosideC39H43NO12S[α]D23=+15.8 (c 0.31, CH2Cl2)Absolute configuration: (1S,2S,3S,4S,5S,7S,1′S,2′R,3′R,4′S,5′R)Source of chirality: d-glucosamine

(1R,2R,3R,4R,5S,6R,7R)-7-Benzyloxy-4,5,6-trihydroxy-5-methoxy-2-methoxycarbonyl-4,5-O-diphenylmethylidenebicyclo[2.2.2]octan-3-yl 2′-acetamido-2′-deoxy-1′-thio-β-d-glucopyranosideC39H45NO12S[α]D23=-37.2 (c 0.31, CH2Cl2)Absolute configuration: (1R,2R,3R,4R,5S,6R,7R,1′S,2′R,3′R,4′S,5′R)Source of chirality: d-glucosamine

(1S,2S,3S,4S,5R,6S,7S)-7-Benzyloxy-4,5,6-trihydroxy-5-methoxy-2-methoxycarbonyl-4,5-O-diphenylmethylidenebicyclo[2.2.2]octan-3-yl 2′-acetamido-2′-deoxy-1′-thio-β-d-glucopyranosideC39H45NO12S[α]D23=+5.6 (c 0.30, CH2Cl2)Absolute configuration: (1S,2S,3S,4S,5R,6S,7S,1′S,2′R,3′R,4′S,5′R)Source of chirality: d-glucosamine

(1R,2S,3R,4R,5R,6R,7R)-7-Benzyloxy-4,5,6-trihydroxy-2-methoxycarbonyl-bicyclo[2.2.2]octan-3-yl 2′-acetamido-2′-deoxy-1′-thio-β-d-glucopyranosideC25H35NO11S[α]D23=-24.5 (c 0.20, CH2Cl2)Absolute configuration: (1R,2R,3R,4R,5S,6R,7R,1′S,2′R,3′R,4′S,5′R)Source of chirality: d-glucosamine

(1S,2R,3S,4S,5S,6S,7S)-7-Benzyloxy-4,5,6-trihydroxy-2-methoxycarbonyl-bicyclo[2.2.2]octan-3-yl 2′-acetamido-2′-deoxy-1′-thio-β-d-glucopyranosideC25H35NO11S[α]D23=+26.1 (c 0.20, CH2Cl2)Absolute configuration: (1S,2R,3S,4S,5S,6S,7S,1′S,2′R,3′R,4′S,5′R)Source of chirality: d-glucosamine

(1R,2S,3R,4R,5R,6R,7R)-4,5,6,7-Tetrahydroxy-2-methoxycarbonyl-bicyclo[2.2.2] octan-3-yl 2′-acetamido-2′-deoxy-1′-thio-β-d-glucopyranosideC18H29NO11S[α]D23=-41.8 (c 0.12, CH2Cl2)Absolute configuration: (1R,2S,3R,4R,5R,6R,7R,1′S,2′R,3′R,4′S,5′R)Source of chirality: d-glucosamine

(1S,2R,3S,4S,5S,6S,7S)-4,5,6,7-Tetrahydroxy-2-methoxycarbonyl-bicyclo[2.2.2] octan-3-yl 2′-acetamido-2′-deoxy-1′-thio-β-d-glucopyranosideC18H29NO11S[α]D23=+28.2 (c 0.12, CH2Cl2)Absolute configuration: (1S,2R,3S,4S,5S,6S,7S,1′S,2′R,3′R,4′S,5′R)Source of chirality: d-glucosamine

(1R,2S,3R,4R,5R,6R,7R)-4,5,6,7-Tetrahydroxy-2-carboxybicyclo[2.2.2]octan-3-yl 2′-acetamido-2′-deoxy-1′-thio-β-d-glucopyranosideC17H27NO11S[α]D23=-51.8 (c 0.18, CH2Cl2)Absolute configuration: (1R,2S,3R,4R,5R,6R,7R,1′S,2′R,3′R,4′S,5′R)Source of chirality: d-glucosamine

(1S,2R,3S,4S,5S,6S,7S)-4,5,6,7-Tetrahydroxy-2-methoxycarbonyl-bicyclo[2.2.2]octan-3-yl 2′-acetamido-2′-deoxy-1′-thio-β-d-glucopyranosideC17H27NO11S[α]D23=+35.4 (c 0.18, CH2Cl2)Absolute configuration: (1S,2R,3S,4S,5S,6S,7S,1′S,2′R,3′R,4′S,5′R)Source of chirality: d-glucosamine