A short synthetic pathway via three-component coupling reaction to tamiphosphor possessing anti-influenza activity

Three-component coupling reaction of (pent-3-oxy)acetaldehyde, (Z)-N-(2-nitrovinyl)acetamide, and tetraethyl 1,1-diylbis(phosphonate) is performed in a one-pot operation, followed by reduction of the nitro group and hydrolysis of the phosphonate ester, to afford 8.7% overall yield of tamiphosphor as a potent neuraminidase inhibitor with IC50 and EC50 values of 2.5 and 31.5 nM against wild-type H1N1 influenza virus. The tamiphosphor (5R)-epimer is a less active anti-influenza agent with IC50 and EC50 values of 39 and 117 nM.