Jean-Noël Volle

Synthesis and evaluation of phosphorus containing, specific CDK9/CycT1 inhibitors.

Although there is a significant effort in the design of a selective CDK9/CycT1 inhibitor, no compound has been proven to be a specific inhibitor of this kinase so far. The aim of this research was to develop novel and selective phosphorus containing CDK9/CycT1 inhibitors. Molecules bearing phosphonamidate, phosphonate, and phosphinate moieties were synthesized. Prepared compounds were evaluated in an enzymatic CDK9/CycT1 assay. The most potent molecules were tested in cell-based toxicity and HIV proliferation assays. Selectivity of shortlisted compounds against CDKs and other kinases was tested. The best compound was shown to be a highly specific, ATP-competitive inhibitor of CDK9/CycT1 with antiviral activity.

A new and convenient method for the synthesis of strong non-ionic bases

Various strong non-ionic phosphazene bases were obtained by a new, efficient and very simple method involving the lithium phosphonium azayldiide Ph3P=NLi as a precursor.

1,1′-Dibenzyl-bis-(triazolyl)diphenylphosphine dioxide: a new efficient organocatalyst for silicon tetrachloride-mediated enantioselective Abramov-type phosphonylation of aldehydes with trialkyl phosphites

Asymmetric phosphonylation of aldehydes with trialkyl phosphites using a combination of SiCl4 and a novel 1,1′-dibenzyl-bis-(triazolyl)diphenylphosphine dioxide organocatalyst has been developed. This protocol provides the corresponding α-hydroxyphosphonates with a broad range of functional groups and substitution patterns in excellent yields and good selectivities.