A convenient method has been developed for the synthesis of diphenyl α-(dipropoxyphosphoramido) alkyl- phosphonates under mild conditions, namely the reaction of dipropyl phosphoramidate (1) with a para-(un)substituted benzaldehyde or cyclicketone (2) and triphenyl phosphite (3) by a one-pot procedure with the aid of acetyl chloride.

N-(1,3,2-Dioxaphosphorinan-2-ylmethyl) thiophosphoramidates were synthesized and determined by NMR spectra and positive ion electrospray ionization mass spectrometry (ESI-MS) in conjunction with tandem mass spectrometry (MS/MS). The fragmentation pathways were investigated. The results show that these characteristic ions in ESI mass spectra are useful in the structural determination of N-(1, 3, 2-dioxaphosphorinan-2-ylmethyl)- thiophosphoramidates.

A series of novel naphthoquinone fused cyclic α-aminophosphonates, 2-alkoxy-3, 4-dihydro-2H-naphtho[2,3-e][1,4,2] oxazaphosphinane-5, 10-dione 2-oxide 3–17 and naphthoquinone fused cyclic α-aminophosphonic monoester 18 were synthesized for the first time. These cyclic α-aminophosphonates were evaluated for antitumor activity on four human tumor cell lines, and three of them showed significant cytotoxicity (IC50: 0.019–5.15 μM) comparable to that of the reference drug doxorubicin. Furthermore, inhibition assays for topoisomerase II-mediated relaxation of supercoiled DNA indicated that the naphthoquinone fused cyclic aminophosphonates were catalytic inhibitors of topoisomerase II.

A convenient and rapid method was developed for the synthesis of various N-phosphoramino α-aminoalkylphosphonates through Mannich type reactions under catalyst- and solvent-free conditions with excellent yields.

A study on the synthesis of the novel cyclic α-aminophosphonates and 2-alkoxy-2- oxo-1, 4, 2-oxazaphosphinanes 4a–r has been carried out. The title compounds were obtained in good yields by one-pot procedure using o-aminophenol, alkyl dichlorophosphinite, and ketones or benzaldehyde. One of their geometric stereoisomers was isolated and characterized. Configurations of 4k and one isomer of 4r have been established by X-ray diffraction analysis. The synthetic methods provide an easy access to the organophosphorus heterocycles with the ring system mentioned above. The abnormal chemical shifts of alkyl-substitute protons in 1H NMR spectra were given reasonable explanation.