Ramon Burgada

A mild and efficient one-pot synthesis of 1-hydroxymethylene-1,1-bisphosphonic acids. Preparation of new tripod ligands

Abstract A simple and efficient one-pot procedure for synthesis of 1-hydroxymethylene-1,1-bisphosphonic acids by reaction of acyl chlorides and tris(trimethylsilyl)phosphite is described. This method was applied to the synthesis of new phosphonated chelating tripod ligands.

Synthese et structure d'un trialcoxy-1,1,1 phospholev premier modele pentacoordine contenant le cycle phosphole

Abstract Addition of a trivalent phosphorus compound to dimethyl acetylenedicarboxylate gives a carbanionic species which can be trapped by dimethyl acetylenedicarboxylate; a trialkoxy-1,1,1 phosphole v is obtained.

Mécanisme de formation et de transformation des spirophosphoranes : III. Synthèse et tautomérie PIII⇌Pv des tétraoxyspirophosphoranes á liaison P-H

Abstract The synthesis of new tetraoxyspirophosphoranes containing a P-H bond has permitted a study by chemical and physicochemical methods of the factors influencing the equilibrium P III ⇌ P v The position of the equilibrium has been determined according to the manner of substitution and the orientation of ring-opening of these cyclic compounds It is shown by variable temperature proton NMR spectroscopy that there is a phenomenon of stereomutation in the pentacovalent structure superposed on this tautometric equilibrium

Bisphosphonate sequestering agents. Synthesis and preliminary evaluation for in vitro and in vivo uranium(VI) chelation

A library of bisphosphonate-based ligands was prepared using solution-phase parallel synthesis and tested for its uranium-binding properties. With the help of a screening method, based on a chromophoric complex displacement procedure, 23 dipodal and tripodal chelates bearing bisphosphonate chelating functions were found to display very high affinity for the uranyl ion and were selected for evaluation of their in vivo uranyl-removal efficacy. Among them, 11 ligands induced a huge modification of the uranyl biodistribution by deviating the metal from kidney and bones to liver. Among the other ligands, the most potent was the dipodal bisphosphonate 3C which reduced the retention of uranyl and increased its excretion by around 10% of the injected metal.

Synthesis of tetradentate mixed bisphosphonates: new hydroxypyridinonate ligands for metal chelation therapy

In a general study for developing better drugs suitable for Fe, Al, Co or lanthanide chelation therapy experiments, new mixed bisphosphonate-hydroxy pyridonates were synthesized. We demonstrate that the method using amidation reaction and dealkylation by concentrated hydrochloric acid gives excellent results for amino bisphosphonic acid ligands having at least two carbons between the amino group and the methylene bisphosphonic acid group.

Reactions de metallation dans la serie des spirophosphoranes a liaison PH. Formation de la liaison PVC

Abstract We report here the generation and reactions of reagents such as A, in which M = Li or Na. The action of various metallation reagents (RLi, R 2 NLi, HNa, NH 2 Na) in THF at room temperature has been tested on 2,2,3,3,7,7,8,8-octamethyl-1,4,6,9-tetraoxy-5-phospha(V)[4.4]spirononane. Only R 2 NLi and NH 2 Na are effective. The metallated intermediate is probably an oxanion rather than a phosphanion. Some coupling reactions of these reagents with various RX and their use in hydroxyspirophosphorane synthesis are described.

Mecanisme de formation et de transformation des spirophosphoranes—I : Synthese de phosphites cycliques de structure et etude de leurs reactions avec les alcools et les glycols

Abstract The preparations of three cyclic diphosphites and their reactions with alcohols and diols are described. A nucleophilic attack on the P atoms gives compounds with either tricoordinated or pentacoordinated phosphorous. These reactions have confirmed previous results on the stability of dioxaphospholane cycles.

Towards a new attenuating compound : A potentiometric, spectrophotometric and NMR equilibrium study on Fe(III), Al(III) and a new tetradentate mixed bisphosphonate-hydroxypyridinonate ligand

Coordination properties toward Fe(III) and Al(III) of a mixed bisphosphonate-hydroxypyridinonate ligand are presented. Potentiometric, spectrophotometric and NMR results allowed to conclude that Fe(III) and Al(III) coordination takes place on the pyridinone moiety. The high steric hindrance prevents the possibility of simultaneous coordination of both groups to the same metal ion. Quantum mechanical calculations confirm this finding allowing to determine the minimal length of the linker necessary for a stable conformation of complexes in which Fe(III) is coordinated both by pyridinone and bisphosphonate groups.

Synthesis of New Phosphonated Tripod Ligands as Putative New Therapeutic Agents in the Chelation Treatment of Metal Intoxications

In a quest for new chelation therapy drugs for the treatment of intoxication by actinides, some new phosphonated chelating tripod ligands have been synthesized. They have been obtained by means of a coupling reaction between a diethylphosphonoalkanoic acid activated with N,N′-disuccinimidyl carbonate (DSC) and a series of polyamines, with subsequent deprotection of the phosphonate groups.

α-DICETO DIPHOSPHONATES ET HYDROXYMETHYLENE TETRAPHOSPHONATES SYNTHÈSE, STRUCTURE ET HYDROLYSE

Abstract Synthesis of methyl esters 3–8 or cyclic esters 3′–8′ of diketo-diphosphonates having n(CH2) are studied. These compounds lead to the corresponding symmetric 3a–8a and 3′a–8′a or disymmetric 3,3′a–8,8′a tetraphosphonates which are isomerized to the phosphates-phosphonates structures 4b–8b and 4′b–8′b. The hydrolysis reactions are also observed.