Preparation of gem-difluorinated retrohydroxamic-fosmidomycin

International audienceFrom several decades, some organophosphorus compounds specifically designed to alterbiological systems were introduced on market as agrochemicals (ie glyphosate and glufosinate asherbicides). Nevertheless, it becomes necessary to find new compounds in order to counter plantresistances already observed with glyphosate. Fosmidomicyn and its N-acetyl analogues FR-900098 were perceived as starting points for elaboration of new herbicide candidates, targetingthe second enzyme of the non-mevalonate pathway in plants, the 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DOXP reductoisomerase or DXR). It is expected that theenhancement of bioactivity compared to the parent compounds, might be reached by insertion oftwo fluorine atoms close to the phosphonate function. Indeed, the presence of both fluorineatoms could improve the lipophilicity, affect the pKa of the phosphonic acid function and theninduce better activities. Herein, the synthesis of gem-difluorinated analogues of retrohydroxamicfosmidomycin and FR-900098-ester is reported using a radical addition mediated by acobaloxime comple

Nouveaux phosphinosucres ou phostines (hétérocycles phosphorés polyhydroxylés à activité anticancéreuse)

Les phosphinosucres appelés aussi phostines sont des analogues phosphorés des sucres pyranoses et des C-arylglycosides. L'évaluation biologique de ses composés a révélé une activité anticancéreuse des phosphinosucres sur les cellules de glioblastome multiforme, un cancer particulièrement malin et invasif qui ne possède pas de solution thérapeutique. Dans le but de comprendre les mécanismes d'action des phosphinosucres et la stéréo-dépendance de leur activité biologique, la caractérisation des diastéréomères de phostines a été menée. Suite à cette détermination structurale, le développement de synthèses diastéréosélectives a permis d'obtenir un mélange fortement enrichi en diastéréomère le plus actif par une séquence réactionnelle qui a mis en jeu une réaction d'oxydation de phosphinosucres -hydroxylés en a-cétophosphinosucres, suivie d'une réduction diastéréosélective. Afin d'améliorer l'activité antiproliférative des phosphinosucres, une diversification chimique a été réalisée. Les variations du groupement aryle lié à l'atome de phosphore nous ont amené à développer une synthèse des aryl-hydrogénophosphinates qui a permis d'obtenir une large variété de ces composés. Par la suite, les aryl-hydrogénophosphinates obtenus ont été engagés dans la synthèse des phostines . De plus, des variations chimiques sur le carbone en position a de l'atome de phosphore ont été entreprises et ont permis l'élaboration de plusieurs composés (triflate, azido, amino, déoxy et triazolyles), puis finalement à l'analogue phosphinosucre du N-acétylglucosamine qui a présenté une importante activité anticancéreuse in vitro.Phosphinosugars also called phostines are new cyclic phosphinates, analogs of carbohydrates and C-aryglycosides, with phosphorus atom mimicking the anomeric carbon. Biological screening tests of these compounds revealed an anticancer activity against glioblastoma multiform, a highly invasive and malignant tumor without curative therapy.With the aim of understanding the phosphinosugars mode of action and their stereo-dependent biological activity, characterization of four phosphinosugars diastereomers formed during the chemical process has been performed. After their structural determination, diastereoselective synthesis enabled us to obtain an enriched mixture of the most active diastereomer based on an oxidation of -hydroxyled phosphinosugars in corresponding -keto phosphinosugars followed by a diastereoselective reduction. Thereafter, antiproliferative activity of phoshinosugars was performed by chemical diversification. Modification of the aryl group linked to phosphorus atom led us to develop aryl-hydrogenophosphinate synthesis to create a broad variety of these structures. Then, the expected aryl-hydrogenophosphinates were used for phostines preparation. Furthermore, chemical modifications on the carbon in a position of phosphorus atom were led and furnished several new compounds (triflate, azido, amino, deoxy and triazolyl), as well as the phosphinosugar analog of N-acetylglucosamine which presented in vitro a high anticancer activity.MONTPELLIER-Ecole Nat.Chimie (341722204) / SudocSudocFranceF

Acyclic to cyclic aminophosphonic and phosphinic acids

International audienceThe results presented in this account deal with the synthesis of acyclic α- or β-aminophosphonates or phosphinates and with the synthesis of heterocyclic compounds, where the phosphorus and/or the nitrogen atoms can be embedded in the heterocyclic core, showing new perspectives in bioactive molecules

Product Class 12: Alkylphosphonium Salts

International audienc

The Tautomeric Persistence of Electronically and Sterically Biased 2-Quinolinones

International audienc

Synthesis and biological applications of phosphinates and derivatives

International audienceThis review first outlines general considerations on phosphinic acids and derivatives as bioisosteric groups. The next sections present key aspects of phosphinic acid-based molecules and include a brief description of the biological pathways involved for their activities. The synthetic aspects and the biological activities of such compounds reported in the literature between 2008 and 2013 are also describe

31.40.3 Arylphosphinic Acids and Derivatives (Update 2018)

International audienc

A new and convenient way fot the synthesis of strong non-ionic bases

International audienceVarious strong non-ionic phosphazene bases were obtained by a new, efficient and very simple way involving the lithium phosphonium azayldiide Ph3P=NLi (2) as a precursor

Reactivity of Ph3PNLi towards PIII and PIV phosphorus electrophiles

International audienceA study of the reactivity of Ph3P]NLi towards phosphorus electrophiles allowed us to develop a general method to isolate, or cleanly generate in situ, a broad family of polyphosphinimines displaying P]N–P bonds. A preliminary application of this methodology is presented here with the synthesis of various Schwesinger-type bases by a simple new procedure employing Ph3P]NLi

Chiral Bisdiphenylphosphine Dioxides Bearing a Bis(triazolyl) Backbone as Promising Lewis Bases for Asymmetric Organocatalysis

International audienceTwo chiral C2‐symmetric diphenylphosphine dioxides bearing an original bis(triazolyl) backbone were prepared starting from inexpensive and readily available precursors. The key step involves the simultaneous formation of five bonds in one chemical step with 100 % atom efficiency through a copper‐catalyzed tandem [3+2] cycloaddition/dimerization reaction. Interestingly, these chiral inducers exhibited good to excellent catalytic activities as chiral Lewis base organocatalysts to promote useful stereoselective reactions