Synthesis of N-(alkoxycarbonyl or alkoxycarbonyl-methyl-alkoxyphosphonyl)-α-amino-O,O-diphenyl phosphonates and their bioactivities

Abstract

With phosphonoformic acid (PFA) and its analog, phosphonoacetic acid (PAA), as the lead compounds, α-amino phosphonates were introduced into PFA and PAA. The derivatives of N-(alkoxycarbonyl-alkoxyphosphonyl)-α-amino phosphonates (I) and N-(alkoxycarbonyl-methyl-alkoxyphosphonyl)-α-amino phosphonates (II) with the N-terminal of amino phosphonates bonding to phosphorus atom of PFA andPAA were synthesized via the reaction of the corresponding phosphonyl chloride with α-amino phosphonates in the presence of a base. The31P NMR spectra of I and II were determined. It is found that the coupling constants3 J pp with R3 being alkyl group were lower than those with R3 being (substituted) phenyl, and this result was discussed. The preliminary bioassay showed that some of the compounds I and II have better activities against tobacco mosaic virus (TMV). The inhibitory was higher than that of DHT (2, 4-dioxyhexahydro-1, 3, 5-triazine). In addition, some of the compounds showed the activity against cancer cells.