Driss El Manouni

α CÉTOPHOSPHONATES ET ESTERS CYCLIQUES D'HYDROXYMÉTHYLÈNES DIPHOSPHONATES SYNTHESES, STRUCTURES ET HYDROLYSE

Abstract Synthesis of symmetrical diesters derived from hydroxy methylene diphosphonic acids 1 to 8 is described either in one step or via the corresponding α ketophosphonate 1a to 8a. Study of the diphosphonates (1 to 6) → phosphate-phosphonates (1b to 6b) isomerization has been realized. Results related to peculiar cases in connection with nonsymmetrical esters 10, 11, 17 and study of the hydrolysis reaction of diphosphonates are presented.

THE MOLECULAR STRUCTURE OF 4-AMINO 1-HYDROXY BUTYLIDENE-1 BISPHOSPHONIC ACID (AHBBPA); AN UNCOMMON ANHYDROUS HYDROXYBISPHOSPHONIC ACID

Abstract The molecular structure of an anhydrous hydroxybisphosphonic acid was determined by X-ray diffraction techniques and compared to the corresponding hydrated crystalline form. The hydrogen bond network and intermolecular interactions show that the polar bisphosphonic group undergoes a rotation to accomodate a different distribution in the hydrophobic/polar zones observed in the crystal packing, while the rest of the amino side chain connected to the functional carbon atom has identical conformation.

Supramolecular assembly of substituted hydroxy-bisphosphonates with cupric ion. Influence of the chain functionalization

Abstract As part of a general study of hydroxy-bisphosphonic acids (HEBP), R-C(OH)(PO3H)2, three Cu (II) complexes with R˭CH3; R˭-(CH2)3-NH2 and R˭-(CH2)5-NH2, were prepared and analysed by X-Ray diffraction methods. The substitution of the methyl group in HEBP (3) by an aminopropyl (1) or by an aminopentyl (2) chain led to a drastic modification of the ionic self-assembly in the crystal and completely different polyhedral complexation networks around the Cu (II). A polymeric chain formation is observed in (3), whereas (1) and (2) display discrete tetrameric and dimeric arrangements. The results are discussed on the basis of the environment of the phosphorus atoms and the molecular geometry around the central carbon atom of the hydroxy-bisphosphonic moiety. These results are further compared to their ability for ionic transport and/or extraction.

1-Hydroxyalkane-1,1-diyldiphosphonates as potent chelating agents for metal ions. Potentiometric and spectroscopic studies of copper(II) co-ordination

Potentiometric and spectroscopic (EPR and absorption) studies have shown that two phosphonic groups bound to the same carbon atom serve as a very powerful binding site for Cu2+ ion in spite of the very high negative charge centred on these groups. The steric effects as well as a high negative charge enforce unusual geometries around the metal ion and the formation of 1:2 complexes is less favourable. These features of the diphosphonic moiety mean that alkoxo-bridged dimer formation via the adjacent hydroxyl groups is less likely.

Synthesis of New Ligands Derived from Polyphosphonates Partial Esters

Abstract: In the search for new chelation therapy drugs for the treatment of metal intoxications, some newpolyphosphonated chelating ligands have been synthesized. They were obtained by means of an Arbuzovreaction followed by addition of the corresponding dialkylphosphite. The regioselective dealkylation wasthen carried out by using trimethylsilyl halide. Keywords : Tetraphosphonate, chelating agents, restrained geometry, partial deprotection.1-Hydroxymethylene-1,1-bisphosphonic acids (or HMBPthroughout) are widely used for the treatment of diseases inthe skeletal system, bone formation and resorption disorders[1] and also for the treatment of cancer [2-5]. It has beenshown that bisphosphonates inhibit the development of bonemetastasis in breast cancer patients [6]. These compoundscontaining a stable P-C-P bridge usually have low toxicityand high stability towards enzymatic degradation. HMBP OPHOO OHMePOOHOH Another property of these compounds largelyinvestigated is their chelating efficiency toward variousmetal ions. Bisphosphonates complexes of

Symmetrical and Unsymmetrical Bishophonate Esters Chemistry: Synthesis, Selective Hydrolysis, Isomerization

Abstract Over thc past few years, bisphosphonatcs have bcen receiving increased auention as a new class of pharmacologically active compound. As a continuation of our research program (1,2,3) in connection with the synthesis of bisphosphonate esw I. we present here some results about thc synthesis of symmetrical and unsymmcuical bisphosphonate esms. These compounds were selectively hydrolizcd to give the following mono, di, d and tcua acids II.

One Pot Synthesis of Bisphosphonate Esters: A Way to Synthesize Tetraphosphonate Esters

Abstract Several methods for the preparation of symmetrical bisphosphonates of general type (RO)2P(O)(R′OH)P(O)(OR)2, have been developed, and investigated for their pharmacological. Pharmacological screening of these bisphosphonates have shown that these compounds have potent cardiovascular activity and are. potentialy useful in the treatment of hypertension. In this work we described of new method “one pot” for the synthesis of hydroxy bis and tetra phosphonates (I, II, III and IV).

Synthesis of 4-Amino-1-Hydroxy-Butane-1,1-Diphosphonate (AHBDP) - Stannous Complexes for the Preparation of Ahbdp-Sn(II)-Tc and its Biodistribution in Rats.

The new potential tracer of bone imaging, AHBDP-Sn(II)-TcO.3H2O was synthesized by reducing the TcO4− to TcO2+ in the presence of AHBDP and Sn(ll)’s reducing agent. We found that tin rapidly forms a stable complex with AHBDP, giving AHBDP-Sn(II).3H2O. In the excess of AHBDP-Sn(ll).3H2O, the AHBDP-Sn(II).3H2O coordinates with TcO2+ to give AHBDP-Sn(II)-TcO.3H2O which could polymerise or oligomerise to give hydrophobic species. The overall process appears as a first-order reaction (K= 0.67 ± 0.005s−1). In rats, the fixation of AHBDP-Sn(II)-99mTcO. 3H2O on bone is homogeneous and the scintigraphic images have the same quality as those of 1-hydroxymethane-1,1-diphosphonate-Technetium (HMDP-99mTc). The activity in non-target organs was neglible.

Attempts to Rationalize the Chemical Reactivity of the 1–3 Dipolar Species Obtained when a Phosphite Reacts with Activated Ethylenic or Acetylenic Ketones or Esters

Abstract - Addition of trivalent phosphorus compounds with α, β ethylenic ketones and esters leads to examples of prototropy or cyclisation or rearrangement with ring expansion from 5 to 7 atoms. When trivalent phosphorus compounds react with acetylenic ketones and esters, the 1, 3 dipolar species can be trapped with an electrophilic reagent (aldehydes or the original acetylenic compound) or a protic reagent (alcohol, acid, amide, phenol, etc…) Ylides, phosphoranes, spirophos-phoranes and phospholes can be obtained.