Sialosyl cation transition-state intermediate

The first substrate-based influenza virus sialidase inhibitor described was Neu5Ac2en (6) [71, 72], It is proposed that the olefin in (6) mimics, to a certain extent, the conformation of the proposed sialosyl cation transition-state intermediate (4) [62,68,69], Neu5Ac2en shows reasonably potent inhibition of influenza virus sialidase (with a A j in the range of 10 5 to 10 6 M) in vitro... 

An alternative approach to the synthesis of compounds which mimic the sialosyl cation transition state intermediate (4) centres on jV-functionalised piperidines like (54) [125]. It is proposed that, upon protonation, the structure (54) would be electronically equivalent to that of resonance contributor (55) of the transition state intermediate (4) which bears the positive charge on the anomeric carbon. Whilst no information is given regarding the activity of compounds such as (54) against influenza sialidase [125], modest inhibition of bacterial sialidases is reported. It remains to be seen what effect, if any, the incorporation of some form of glycerol side-chain in this new struc-... 

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