Premium
Carbohydrate Natural Products as a Scaffolding for the Preparation of Potential Neuraminidase Inhibitors
Author(s) -
Maione Anna M.,
Giordani Emma,
Costa Mara,
Spirito Alessandra
Publication year - 1997
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.19973300105
Subject(s) - chemistry , sialidase , phosphonate , neuraminidase , hydrolysis , amberlite , organic chemistry , sodium hydroxide , aqueous solution , hydroxymethyl , carbohydrate , stereochemistry , enzyme , adsorption
Compound 10b , 6‐acetamido‐6,8‐dideoxy‐D‐ erythro ‐β‐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 × 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(hydroxy‐methyl) phosphonate as acceptor, also displays an inhibitory activity towards Clostridium perfringens sialidase ( K i in mM range as with Neu5Ac).