Synthesis and Antimicrobial Activity of Novel Iminophosphocin Derivatives

Iminophosphocins 8a-8e and 9a-9e were synthesized in four-step reactions via Staudinger reaction. 3-(Bromomethy 1)-1,2,3,4,5 -pentahydro-3 lambda(5)-naphtho[1,8-f,g][1,5,3]diazaphosphocin-3-one (3) was prepared by reacting tris(bromomethyl)phosphineoxide (1) with 1,8-diaminonaphthalene (2) in the presence of triethylamine (TEA) in dry tetrahydrofuran (THF), and treated with L-valine methyl ester (4) and bis(2-chloroethyl)amine (5) in the presence of TEA in dry THF to get 3-methyl-2-[(3-oxo-1,2,3,4,5-pentahydro-3 lambda(5)-naphtho[1,8-f,g][1,5,3]diazaphosphocin-3-yl)methylamino]butanoate (6) and 3-[di(2-chloroethyl)aminomethyl]-1,2,3,4,5-pentahydro-3 lambda(5)-naphtho[1,8-f,g][1,5,3]diazaphosphocin-3-one (7). The compounds 6 and 7 were treated with trichlorosilane (SiCl3H) in dry tetrahydrofuran (THF) to form the trivalent P(III) intermediates 8 and 9, which were further treated with various alkyl azides in dry THF in 55-60 degrees C to afford the title compounds 8a-8e and 9a-9e. Their structures were established by multi-nuclear NMR and mass spectra. All the newly synthesized compounds were found to possess moderate anti-microbial activity.