Synthesis and anti-Influenza virus activity of 7-O-Alkylated derivatives related to zanamivir

Synthesis and Anti-influenza Evaluation of Polyvalent Sialidase Inhibitors Bearing 4-Guanidino-Neu5Ac2en Derivatives

“…30) 10 was converted to 7-Oalkylated zanamivir derivatives 13 using conventional methods via intermediates 4-azide compounds 11, and 4-guanidino compounds 12 (Chart 3). [18][19][20][21][22] To further develop compounds 13, we modified the terminal position of the alkyl groups to allow coupling with the polymer backbone (Chart 4). Treatment of 8 with potassium hydroxide followed by di(benzyloxyethyl)-or di(benzyloxypentyl)-sulfate gave 14j and 14k, respectively.…”

From Neuraminidase Inhibitors to Conjugates: A Step Towards Better Anti-Influenza Drugs?

“…Honda and coworkers [78] have demonstrated that the ZA analogs 30a and 30b having the 7-OH replaced by fluorine atom or azido group showed improved anti-influenza activity (Figure 9). The 7-alkyl ether derivatives of ZA, for example 31a-c, still retained good anti-influenza activity with EC 50 in low nanomolar range [79]. The ZA derivatives 32a-c having dihydroxy-oxacycles in lieu of the glycerol side chain also showed the antiinfluenza activity as potent as ZA [80].…”

“…The ZA derivatives 32a-c having dihydroxy-oxacycles in lieu of the glycerol side chain also showed the antiinfluenza activity as potent as ZA [80]. However, the 8,9-deoxy analogs of 7-O-alkyl-ZA (33a-c) lost the antiviral activity [79]. Andrews and co-workers [ found that ZA analogs 34a and 34b with modification of 7-OH to carbamates did not cause significant reduction in anti-influenza activity.…”

Enzyme‐Catalyzed Aldol Additions

“…Fluoro-tagged sialic acid analogs are accessible by NeuA-catalyzed aldol addition of pyruvate to 2-(perfluorohexyl)ethoxymethyl derivatives of ManNAc (Scheme 8.6) [34]. Derivatives of NeuA with hydrophobic substituents are recently gaining interests as analogs of the potent anti-flu zanamivir (35) [35]. The corresponding starting materials for their synthesis are also of interest, for example, ManNAc analogs 36 and 37, particularly when they are going to be acceptors for key aldol addition with pyruvate catalyzed by NeuA aldolase from E. coli.…”