Tadeusz Gajda

A convenient synthesis of O-ethyl-1-aminoalkylphosphinates

Abstract 1-Aminoalkylphosphinates 4 have been obtained in good yields in a one-step transformation by the Mitsunobu reaction of 1-hydroxyalkylphosphinates 1 with hydrazoic acid, and subsequent treatment of the intermediate azides 2, with triphenylphosphine, followed by hydrolysis of the iminophosphoranes 3 with water.

Preparation of diethyl 1-bromoalkylphosphonates

Abstract Diethyl 1-bromoalkylphosphonates 1 have been obtained in good to moderate yields by the reaction of diethyl I-hydroxyalkylphosphonates 2 with the triphenylphosphine-carbon tetrabromide system or dibromotriphenylphosphorane.

Differentiation of Diastereoisomers of Protected 1,2-Diaminoalkylphosphonic Acids by EI Mass Spectrometry and Density Functional Theory

AbstractElectron ionization mass spectrometry and density functional theory (DFT) calculations have been used to study the fragmentation of diastereoisomers of protected 1,2-diaminoalkylphosphonic acids. The loss of a diethoxyphosphoryl group and the elimination of diethyl phosphonate were found to be competitive fragmentation processes, which can be used to differentiate both stereoisomers. Selective deuterated analogs and product- and precursor-ion mass spectra allowed the elucidation of the fragmentation mechanisms. The structures of the transition states and product ions were optimized using the density functional theory (DFT), and free energy calculations confirmed the observed differences in the formation and relative intensities of specific fragment ions. Figureᅟ

Microwave-assisted synthesis of dialkyl ω-azidoalkylphosphonates

ABSTRACT An efficient and reproducible microwave-assisted synthesis of dialkyl ω-azidoalkylphosphonates via nucleophilic substitution of the appropriate dialkyl ω-bromoalkylphosphonates by sodium azide in water or dimethylformamide (DMF) as solvent has been developed. This process has been optimized for batch reactors. The target, structurally diverse dialkyl ω-azidoalkylphosphonates with different steric hindrance around the phosphonato groups and containing unbranched side carbon chains of different lengths (n = 2–6), has been obtained in moderate to high yields (39–87%). GRAPHICAL ABSTRACT

Design, Synthesis, and Evaluation of ω-(Isothiocyanato)alkylphosphinates and Phosphine Oxides as Antiproliferative Agents

A series of 21 novel, structurally diverse ω‐(isothiocyanato)alkylphosphinates and phosphine oxides (ITCs) were designed and synthesized in moderate to good yields. The synthesized compounds were evaluated for in vitro antiproliferative activity using LoVo and LoVo/DX cancer cell lines. The biological activity of the synthesized compounds was higher than that of natural isothiocyanates such as benzyl isothiocyanate or sulforaphane. The antiproliferative activity of selected ITCs was also tested on selected cancer cell lines: A549, MESSA and MESSA/DX‐5, HL60 and HL60MX2, BALB/3T3, and 4T1. These compounds were assessed for their mechanism of action as inducers of cell‐cycle arrest and apoptosis. Ethyl (6‐isothiocyanatohexyl)(phenyl)phosphinate (71) was tested in vivo on the 4T1 cell line and demonstrated moderate antitumor activity, similar to that benzyl isothiocyanate and cyclophosphamide.

Investigation of the reaction of (R)-(+)- and (S)-(−)-α-methylbenzylammonium hypophosphites with benzaldehyde

GRAPHICAL ABSTRACT ABSTRACT Model reaction of (R)- and (S)-α-methylbenzylammonium hypophosphites with benzaldehyde was discussed in detail. The appropriate (R,S)- or (S,R)- vs (R,R)- or (S,S)-aminophosphinic acid derivatives were formed with low diastereoselectivity (dr = 1.1:1–4.1:1). The impact of different reaction conditions on diastereoselectivity and the influence of solvent on crystallization of the major (S,R)- or (R,S)-aminophosphinic acids were evaluated. Plausible mechanism of the reaction was presented. Preferential formation of diastereomeric (S,R)- or (R,S)-aminophosphinic acids was explained on the basis of PM6 semi-empirical calculations.