Abstract
Ph.D. (Chemistry)
This thesis was devoted to the synthesis of new bisphosphonates molecules, the study of their reactivity and the evaluation of their biological activities. The synthesis of epoxyalkylgembisphosphonates was carried out in three steps. The first step was the synthesis of arynyl and alkynylphosphonates by metallation of alkyl and aryl acetylenes followed by condensation with diethylchlorophosphate at low temperature. The second step was the synthesis of vinylgembisphosphonates by a tributylphosphine catalyzed phosphorylation of arynylphosphonates. The last step to epoxyalkylgembisphosphonates was achieved by oxidation of vinylgembisphosphonates using ethylmethyldioxirane generated in situ from potassium monopersulfate (caroate) and butanone in a phase transfer system. The synthesized epoxyalkylgembisphosphonates were studied in order to assess their reactivity with different nucleophiles and their chemical usefulness. All the synthesized compounds were characterized by nuclear magnetic resonance (NMR) spectroscopy, infrared (IR) spectroscopy and mass spectrometry (GCxGC-TOF-MS). In term of reactivity, epoxyalkylgembisphosphonates were found to be less reactive than epoxyphosphonates. As far as their biological activities are concerned, epoxyalkylgembisphosphonates were found to be more potent than some commercially available antibiotics.