One-Pot Synthesis of Phosphinylphosphonate Derivatives and Their Anti-Tumor Evaluations |
| |
Authors: | Jade Dussart-Gautheret Julia Deschamp Thibaut Legigan Maelle Monteil Evelyne Migianu-Griffoni Marc Lecouvey |
| |
Affiliation: | Department of Chemistry, Université Sorbonne Paris Nord, CSPBAT, CNRS, UMR 7244, 1 rue de Chablis, F-93000 Bobigny, France; (J.D.-G.); (J.D.); (T.L.); (M.M.) |
| |
Abstract: | This paper reports on the synthesis of new hydroxymethylene-(phosphinyl)phosphonates (HMPPs). A methodology has been developed to propose an optimized one-pot procedure without any intermediate purifications. Various aliphatic and (hetero)aromatic HMPPs were synthesized in good to excellent yields (53–98%) and the influence of electron withdrawing/donating group substitution on aromatic substrates was studied. In addition, the one-pot synthesis of HMPP was monitored by 31P NMR spectroscopy, allowing effective control of the end of the reaction and identification of all phosphorylated intermediate species, which enabled us to propose a reaction mechanism. Optimized experimental conditions were applied to the preparation of biological relevant aminoalkyl-HMPPs. A preliminary study of the complexation to hydroxyapatite (bone matrix) was carried out in order to verify its lower affinity towards bone compared to bisphosphonate molecules. Moreover, in vitro anti-tumor activity study revealed encouraging antiproliferative activities on three human cancer cell lines (breast, pancreas and lung). |
| |
Keywords: | phosphinylphosphonate bisphosphonate bisphosphinate synthesis anti-tumor activity |
|
|