Carbohydrate natural products as a scaffolding for the preparation of potential neuraminidase inhibitors.
Compound 10b, 6-acetamido-6,8-dideoxy-D-erythro-beta-D- galacto-octopyranosyl-1-oxyacetic acid sodium salt, was synthesised by hydrazinolysis of Lincomycin, acetylation of methylthiolincosaminide (MTL) 9a, and by subsequent glycosylation of acetate 9b with methyl glycolate under mild conditions (NIS/TfOH). The methyl ester 10a was hydrolysed by treatment with Amberlite Ira-4OO (OH-) resin and aqueous sodium hydroxide, followed by neutralisation with Dowex-50 W x 8 (H+) resin and lyophilisation to give 10b. This carboxylate may represent the first derivative in a novel series of sialidase inhibitors utilising carbohydrate natural products. The phosphonate 11c, prepared under the same experimental conditions with dibenzyl(hydroxymethyl)phosphonate as acceptor, also displays an inhibitory activity towards Clostridium perfringens sialidase (Ki in mM range as with Neu5Ac).
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Centro di Studio per la Chimica del Farmaco C.N.R., Rome, Italy.
Giordani
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Costa
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Spirito
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D000085:Acetates / Q000138:chemical synthesis; D000606:Amino Sugars / Q000138:chemical synthesis; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002241:Carbohydrates / Q000138:chemical synthesis* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis*; D008034:Lincomycin / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D009439:Neuraminidase / Q000037:antagonists & inhibitors*
C106121:6-acetamido-6,8-dideoxy-erythro-galacto-octopyranosyl-1-oxyacetic acid; D000085:Acetates; D000606:Amino Sugars; D000900:Anti-Bacterial Agents; D000998:Antiviral Agents; D002241:Carbohydrates; D004791:Enzyme Inhibitors; D008034:Lincomycin; D009439:Neuraminidase