Carbohydrate Natural Products as a Scaffolding for the Preparation of Potential Neuraminidase Inhibitors

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).