Abstract
The aim of this project was to synthesize novel bisphosphonic acid derivatives, study their reactivity and test them for antibacterial, antimalarial and antitrypanosomal activity. The first step towards the target compounds was the synthesis of substituted vinylgembisphosphonates by Knoevenagel condensation between aromatic aldehydes and tetraethylmethylenebisphosphonate. The vinyl bisphosphonates were then oxidized using hydrogen peroxide to give aryl substituted epoxygembisphosphonates. 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) catalysed and microwave assisted reactions of the epoxy bisphosphonates gave mixtures of phosphinyl phosphonate diastereomers due to phosphonate phosphate rearrangement of bisphosphonates under basic conditions and high temperatures. A new class of compounds analogous to the pyrophosphate, 1,4-azaphosphinane-3-phosphonates, were synthesized by phospha-Dieckmann condensation of amino diphosphonate. The vinylgembisphosphonates were deprotected by reacting with bromotrimethylsilane followed by methanolysis to give bisphosphonic acids. Epoxygembisphosphonates were dealkylated with dibutylamine to give novel aryl substituted dibutylammonium diethyl epoxygembisphosphonates salts. The compounds synthesized were characterised by nuclear magnetic resonance (NMR) spectroscopy, Fourier transformed infrared spectroscopy (FT-IR) and mass spectrometry...
Ph.D. (Chemistry)