Synthesis and preliminary anticancer evaluation of photo-responsive prodrugs of hydroxymethylene bisphosphonate alendronate.

The antitumoral activity of hydroxymethylene bisphosphonates (HMBP) such as alendronate or zoledronate is hampered by their exceptional bone-binding properties and their short plasmatic half-life which preclude their accumulation in non-skeletal tumors. In this context, the use of lipophilic prodrugs represents a simple and straightforward strategy to enhance the biodistribution of bisphosphonates in these tissues. We describe in this article the synthesis of light-responsive prodrugs of HMBP alendronate.

Synthesis of Aminobisphosphinates through a Cascade Reaction between Hypophosphorous Acid and Bis(trimethylsilyl)imidates Mediated by ZnI.

Among phosphorylated derivatives, phosphinates occupy a prominent place due to their ability to be bioisosteres of phosphates and carboxylates. These properties imply the necessity to develop efficient methodologies leading to phosphinate scaffolds. In recent years, our team has explored the nucleophilic potential of silylated phosphonite towards various electrophiles.

One-Pot Synthesis of Phosphinylphosphonate Derivatives and Their Anti-Tumor Evaluations.

This paper reports on the synthesis of new hydroxymethylene-(phosphinyl)phosphonates (HMPPs). A methodology has been developed to propose an optimized one-pot procedure without any intermediate purifications. Various aliphatic and (hetero)aromatic HMPPs were synthesized in good to excellent yields (53-98%) and the influence of electron withdrawing/donating group substitution on aromatic substrates was studied.

Synthesis and preliminary anticancer evaluation of new triazole bisphosphonate-based isoprenoid biosynthesis inhibitors.

The synthesis of a new set of triazole bisphosphonates 8a-d and 9a-d presenting an alkyl or phenyl substituent at the C-4 or C-5 position of the triazole ring is described. These compounds have been evaluated for their antiproliferative activity against MIA PaCa-2 (pancreas), MDA-MB-231 (breast) and A549 (lung) human tumor cell lines. 4-hexyl- and 4-octyltriazole bisphosphonates 8b-c both displayed remarkable antiproliferative activities with IC values in the micromolar range (0.

Formation of 1-Hydroxymethylene-1,1-bisphosphinates through the Addition of a Silylated Phosphonite on Various Trivalent Derivatives.

An easily handled one-pot synthetic procedure was previously developed for the synthesis of bisphosphinates starting from acyl chlorides. Herein, other trivalent derivatives as acid anhydrides and activated esters were tested to form various bisphosphinates. This modulation of the reactivity can be controlled according to the nature of the acid derivative for the use of sensitive and functionalized substrates.

A convenient synthetic route towards H-bisphosphinates.

A practical generalisable procedure to synthesize hydroxymethylene H-bisphosphinates has been optimised. Unlike previous reports, numerous alkyl (including an alendronate bisphosphinate analogue) or (hetero)aryl compounds were rapidly obtained in satisfactory to excellent yields. A side product could have been identified as a phosphino-phosphonate isomer and plausible mechanistic pathways are proposed here.

Bifunctional Tripeptide with a Phosphonic Acid as a Brønsted Acid for Michael Addition: Mechanistic Insights.

Enamine catalysis is a widespread activation mode in the field of organocatalysis and is often encountered in bifunctional organocatalysts. We previously described H-Pro-Pro-pAla-OMe as a bifunctional catalyst for Michael addition between aldehydes and aromatic nitroalkenes. Considering that opposite selectivities were observed when compared to H-Pro-Pro-Glu-NH , an analogue described by Wennemers, the activation mode of H-Pro-Pro-pAla-OMe was investigated through kinetic, linear effect studies, NMR analyses, and structural modifications.

Towards potential nanoparticle contrast agents: Synthesis of new functionalized PEG bisphosphonates.

The use of nanotechnologies for biomedical applications took a real development during these last years. To allow an effective targeting for biomedical imaging applications, the adsorption of plasmatic proteins on the surface of nanoparticles must be prevented to reduce the hepatic capture and increase the plasmatic time life. In biologic media, metal oxide nanoparticles are not stable and must be coated by biocompatible organic ligands.

Cavitand supported tetraphosphine: cyclodextrin offers a useful platform for Suzuki-Miyaura cross-coupling.

The cyclodextrin-tetraphosphine hybrid coined α-Cytep allows turnover numbers up to 340,000,000,000 and turnover frequencies up to 1,000,000,000 h(-1) to be reached in Suzuki-Miyaura reactions. These exceptional figures are clearly linked to the outstanding longevity of the reactive species induced by the ligand α-Cytep and illustrates the rising potential of cyclodextrins in catalytic applications.

Towards a stable noeuromycin analog with a D-manno configuration: synthesis and glycosidase inhibition of D-manno-like tri- and tetrahydroxylated azepanes.

Noeuromycin is a highly potent albeit unstable glycosidase inhibitor due to its hemiaminal function. While stable D-gluco-like analogs have been reported, no data are available for D-manno-like structures. A series of tri- and tetrahydroxylated seven-membered iminosugars displaying either a D-manno-or a L-gulo-like configuration, were synthesized from methyl α-D-mannopyranoside using a reductive amination-mediated ring expansion as the key step.

Efficient construction of polycyclic derivatives via a highly selective CuI-catalyzed domino reductive-aldol cyclization.

A versatile methodology for the diastereo- and enantioselective domino reductive-aldol cyclizations is reported. By using a copper (I)/diphosphane ligand, various five- and six-membered rings were generated with good to excellent diastereo- and enantioselectivities (cis:trans up to 100:0 and ee up to 95%).

Copper(I)-catalyzed enantio- and diastereoselective tandem reductive aldol reaction.

[Structure: see text] An efficient method for the enantioselective tandem reductive aldol reaction of methyl acrylate with aldehydes is reported. By using a copper(I) precursor and a proper diphosphane ligand, high reactivities can be reached, with TOF up to 40,000 h-1. Taniaphos-based ligands lead to enantioselectivities of up to 97% in the case of the major syn diastereoisomer.