Methyl [hydr­oxy(phen­yl)phosphono­meth­yl]phospho­nate methanol solvate

The title compound, C8H12O7P2·CH4O, is a monoesterified bis­phospho­nate (or 1-hydroxy­methyl­ene-1,1-bis­phospho­nic acid). These synthetic compounds are widely used in medicine to inhibit bone resorption in diseases like osteoporosis, and are characterized by a stable P—C—P group and are thus analogs of inorganic pyrophosphate. By masking one or several ionizable groups, introduced as phosphono­ester, it was anti­cipated the formation of prodrugs with higher lipophilicity that could facilitate the drug delivery and metabolization. Mol­ecules are paired by inter­molecular hydrogen bonds involving the phospho­nic groups. In addition, dimers are connected side-by-side, building infinite ribbons along the a-axis direction; these ribbons are cross-linked perpendicularly along the b-axis direction via a methanol solvent mol­ecule (disordered over two sites with occupancy factors ca 0.6 and 0.4), forming an extended inter­molecular hydrogen-bonded network. The H atoms of the methyl group in the main molecule are disordered equally over two positions

Adaptation of the base-paired double-helix molecular architecture to extreme pressure

The behaviour of the d(GGTATACC) oligonucleotide has been investigated by X-ray crystallography at 295 K in the range from ambient pressure to 2 GPa (∼20 000 atm). Four 3D-structures of the A-DNA form (at ambient pressure, 0.55, 1.09 and 1.39 GPa) were refined at 1.60 or 1.65 Å resolution. In addition to the diffraction pattern of the A-form, the broad meridional streaks previously explained by occluded B-DNA octamers within the channels of the crystalline A-form matrix were observed up to at least 2 GPa. This work highlights an important property of nucleic acids, their capability to withstand very high pressures, while keeping in such conditions a nearly invariant geometry of base pairs that store and carry genetic information. The double-helix base-paired architecture behaves as a molecular spring, which makes it especially adapted to very harsh conditions. These features may have contributed to the emergence of a RNA World at prebiotic stage

Synthèses d'analogues thiophéniques des paullones, agents antitumoraux potentiels

METZ-SCD (574632105) / SudocSudocFranceF

From Industrial Method to the Use of Silylated P(III) Reagents for the Synthesis of Relevant Phosphonylated Molecules

International audiencePhosphonates and their derivatives widely represent important pharmacophores in various classes of therapeutic agents from antivirals to antibiotics. Among these phosphonylated compounds, 1-hydroxymethylene-1,1-bisphosphonates (HMBPs) have occupied a very important place for 30 years now and are currently used in medicine for their inhibitory properties on bone resorption. HMBPs also exhibit direct and indirect antitumor effects in vitro against a broad variety of tumor cell lines, including melanoma, mesothelioma, prostate, breast, lung, and myeloma cancer cells. This review will discuss the various syntheses of bisphosphonates with the goal of illustrating their potential interest for the development of therapeutic agents. We will also disclose our latest achievements in phosphinate chemistry

Impact of alendronate and VEGF-antisense combined treatment on highly VEGF-expressing A431 cells

1 - ArticleBisphosphonates, and more specially nitrogen-containing bisphosphonates, which are in current use for the treatment of bone diseases, demonstrate proapoptotic, antiproliferative, antiangiogenic and anti-invasive properties on tumor cells. The amino-bisphosphonate alendronate is considered as a potential anticancer drug. In the case of A431 cells, which express high levels of VEGF, it had a two-step effect. At 24 h, the antitumor properties of alendronate were counterbalanced by a survival process, which consisted of an enhancement of VEGF expression (mRNA and protein secretion) and TGF[alpha] secretion. It was only at 48 h that alendronate displayed the expected antiproliferative and antiangiogenic properties. The first step, in which the PI3K pathway was engaged, could be prevented by the use of a VEGF-antisense oligonucleotide. The combination of such an antisense with small concentrations of alendronate (~2 [mu]M), which is of the order of clinically used concentrations, was shown to have an antiangiogenic effect as soon as 12 h

A convenient one-pot synthesis of 1-hydroxymethylene-1,1-bisphosphinic acids

International audienceA convenient and generalizable procedure has been optimized to access to 1-hydroxymethylene-1,1-bisphosphinate compounds. Several alkyl, including an alendronate bisphosphinate analog, and (hetero)aryl compounds were rapidly obtained in satisfying to excellent yields. A side product could be identified as a phosphino-phosphonate isomer and plausible mechanistic pathways are discussed here

A General Protocol for the Synthesis of H-α-Hydroxyphosphinates Jade Dussart Julia Deschamp* 0 0 0 0 - 0 0 0 2 - 1 9 7 9 - 6 9 1 3 Maelle Monteil Scheme 1 Synthetic pathways to phosphinates and H-phosphinates

International audienceA general synthetic procedure was developed for H-α-hydroxyphosphinates via Abramov reaction. The present work is a complementary study to hose reported till now. This methodology has the advantage that it can be applied to various aliphatic and (hetero)aromatic substrates. The H-α- hydroxyphosphinates were easily purified and obtained in good to excellent yields in shorter times. A 31P NMR spectroscopy study has shown that only 2 equivalents of a silylating agent were required

Design and synthesis of new polyphosphorylated upper-rim modified calix[4]arenes as potential and selective chelating agents of uranyl ion

1 - ArticleNew upper-rim polyphosphorylated calix[4]arenes were designed for decorporation of uranium in case of nuclear contamination. A ligand system containing four preorganized 1-hydroxymethylene-1,1-bisphosphonic acid moieties anchored onto a calix[4]arene platform has been developed. Three calix[4]arene-bisphosphonates were efficiently prepared in multi-step syntheses with a variable carbon chain length between the bisphosphonate and the calix[4]arene. Affinity constants towards uranyl ion were determined and compared with those of bis(HEDP) and tris(HEDP) phosphonates, known as efficient ligands for uranyl

Peptides holding a phosphonic acid: Easily recyclable organocatalysts for enantioselective C–C bond creation

A novel bifunctional organocatalysts library was developed as efficient tool for the stereoselective Michael addition of aldehydes with several aromatic nitroalkenes. Therefore, a phosphonic acid was used for the very first time as activating moiety in the field of organocatalysis. H-R-ProS Pro -R-pAla 1-OMe was identified as the most effective one with up to 95:5 d.r. and 93:7 e.r over 12 GABA precursors examples. This catalyst was easily recycled and reused over 10 cycles without any significant loss of selectivity