D. El Manouni

The Efficacies of 3,4,3-LIHOPO and DTPA for Enhancing the Excretion of Plutonium and Americium from the Rat: Comparison with Other Siderophore Analogues

With DTPA as a comparison, the siderophore analogue code named 3,4,3-LIHOPO has been tested for its ability to remove 238Pu and 241Am from rats after their inhalation or intravenous injection as nitrate. The most effective treatment regimen for inhaled Pu was the repeated administration of 30 mumol kg-1 3,4,3-LIHOPO. By 7 days after exposure, the Pu contents of the lungs and total body were reduced respectively to 2 and 4% of those in untreated animals. These values were six and three times less than when DTPA was administered using the same protocol. For inhaled Am, 3,4,3-LIHOPO and DTPA were considered equally effective, the lung and total body contents being reduced respectively to 13 and 10% of those in controls. Some animals showed slight degenerative changes in the liver and proximal tubules of the kidneys after the repeated administration of 30 mumol kg-1 of 3,4,3-LIHOPO; however these changes were less marked than after DTPA treatment. After the intravenous injection of Pu, the most effective regimen was the single administration of 3 mumol kg-1 3,4,3-LIHOPO. The body content at 7 days was reduced to 7% controls compared with 19% after the repeated administration of 30 mumol kg-1 DTPA. At a dosage of 30 mumol kg-1, 3,4,3-LIHOPO was less effective owing to the higher retention of Pu in the liver. With repeated dosages of 30 mumol kg-1 3,4,3-LIHOPO was more effective than DTPA for the decorporation of Am; the body contents were 16 and 31% of those in controls respectively. Importantly, the body content was still reduced to 28% of control after a single administration of 3 mumol kg-1. The ligand 3,4,3-LIHOPO, which is also superior to other siderophore analogues, could represent a most significant development in the decorporation of Pu and Am.

ETUDE STRUCTURALE DE L'ACIDE BUTANE HYDROXY-1 AMINO-4 DIPHOSPHONIQUE-1,1′

Abstract Structural study using X-Ray Crystallography of the amino hydroxy diphosphonic acid of the title has been done. The final objective is to use this functionalized hydroxy diphosphonic acid in complexation study and in organic synthesis of biological derivatives by the way of the amino group. Results are discussed on the basis of the environment of phosphorus atoms and on the molecular geometry around the central carbon atom.

SYNTHÈSE D'α CÉTOPHOSPHONATES ET D'ESTERS D'HYDROXY MÉTHYLÈNE DIPHOSPHONATES III

Abstract The phenylacetic chloride reacts with the trimethyl phosphite and the methoxy tetramethyl dioxaphospholane to give hydroxyvinyl phosphonates 1 and 6 which are starting products in the synthesis of diphosphonates 11 and 16. The reactions of crotonyl chloride a, trans cinnamoyl chloride b, methacryloyl c and dimethyl acryloylchloride d with the same phosphites are also studied. Stable spirophosphoranes 26′, 29 and 25′ are obtained from methoxy tetramethyl dioxaphospholane and a, b, c respectively; d leads quantitatively to the formation of a stable keto phosphonate 27.

ETUDE STRUCTURALE DU TÉTRAESTER MÉTHYLIQUE DE L'ACIDE ETHANE HYDROXY-1 DIPHOSPHONIQUE-1,1′ ET DU TETRAESTER MÉTHYLIQUE DE L'ACIDE MÉTHANE HYDROXY-1 PHÉNYL-1 DIPHOSPHONIQUE-1,1′

Abstract Structural study using X-Ray crystallography of the two symmetrical diesters 1 and 2 of the titles has been done. Results are discussed on the basis of the environment of phosphorus atoms and on the molecular geometry around the central carbon atom.

NOUVELLE MÉTHODE DE PRÉPARATION D'ESTERS HYDROXY BISPHOSPHONIQUES SYMÉTRIQUES

Abstract A one pot synthesis of symmetric methyl, benzyl hydroxy bisphosphonic esters can be obtained, without the use of a dialkylphosphite by introducing a protic reagent which removes the usual α-ketophosphonate step.

A Simple and Efficient Procedure for the Synthesis of an Alendronate- Oligonucleotide Conjugate via a Carbamate Linker

Abstract In order to combine the biological properties of oligonucleotides, a synthetic chemical modelized reaction was performed and the procedure then applied to the preparation of an alendronate-deoxyoligonucleotide conjugate through a carbamate linker.

SYNTHESIS OF NEW α-KETOPHOSPHONATES

Abstract Using the Arbuzov reaction, asymmetrical or symmetrical benzyl α-ketophosphanates can be synthesized. In the case of symmetrical benzyl α-ketophosphonates, it was observed that the modification of benzyl groups influences the yield of the Arbuzov reaction.

REACTIONS DES DIOXAPHOSPHOLANES AVEC LES ETHYLENIQUES CARBONYLES ORIENTATION VERS LA FORMATION D'YLURES OU DE PHOSPHORANES

Abstract The reactions of cyclic phosphites and aminophosphines 1 to 4 with trans dibenzoyleethylene, methyl-fumarate, benzalacetone, 2-pentenoicacid-4-one-methylester and benzalacetophenone has been investigated. These reactions lead either to ylid formation 23, 24 and 25 or to spirophosphoranes formation 5, 6, 15 to 20. Some of these phosphoranes behave only as intermediate species and undergo a rearrangement reaction with ring expansion from 5 to 7 bonds 8, 13, 22. Attempts to rationalize these reactions and mechanisms schemes are proposed.

Synthèse et réactivité d'un ester cyclique d'α-aminodiphosphonate. II

Abstract The reactions of methoxy dioxaphospholan and corresponding hydrogen phosphonate 1 with (MeN = CHCl)Cl, (MeO)2CHNMe2 and MeOCH2NMe2 have been studied. These reactions lead either to amino diphosphonate 5 or to amino phosphonate 3 and phosphate 2. The hydrolysis and methanolysis reactions of 5 are also presented.

ETUDE STRUCTURALE DU(N,N-DIMETHYLAMINOCARBONYL-l-METHOXYCARBONYL-2-ETHENYL(Z))-2-OXO-2-TETRAMETHYL- 4,4,5,5-DIOXAPHOSPHOLANE-1,3,2. PHENOMENE DE PREFIGURATION A L'ETAT SOLIDE D'UN INTERMEDIAIRE REACTIONNEL PENTACOORDINE

Abstract Phosphonate 2 is obtained by hydrolysis of the spirophosphorane 1. IR. 1H and 31P NMR spectra confirm the phosphonate structure. However, one question remains about the relative position of the amide group and ester function relative to the phosphonate group. We resolved this difficulty through X-ray crystallography of 2. Phosphonate 2 structure shows a slightly distorted figure of the spirophosphorane 1 of which it comes from. This observation is quite astonishing because of the many possible carbonyl positions of the new ester function. We can reasonably rationalize this phenomenon as the prefiguration of a pentacoordinated chemical intermediate which permits to explain easily the opposite reaction for the PIV → Pv way. So, phosphonate 2 structure is in between two pentacoordinate structures.