PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 12489219

Easy access to phosphonothioates.

Pierre-Yves Renard·Hervé Schwebel·Philippe Vayron·Ludovic Josien·Alain Valleix·Charles Mioskowski
View original source ↗Export metadata ↓

Abstract

A new and particularly mild method for the formation of phosphorus-sulfur bonds has been achieved through base-catalyzed addition of thiocyanate to the corresponding H-phosphine oxide, phosphinate, or phosphonate. This reaction procedure offers many advantages: the use as starting material of a stable and not oxygen-sensitive phosphorus(v) species, particularly mild and nonaqueous reaction conditions and workup (a pivotal point for these sensitive phosphonothioates), and, through optimized access to thiocyanates, a wider scope of substrates. This method has been applied to achieve the synthesis of substrate analogues for the study of antibody-catalyzed hydrolysis of acetylcholinesterase inhibitor PhX (11).

Explore related subjects

Cholinesterase InhibitorsEnzyme InhibitorsOrganophosphonatesOrganothiophosphorus CompoundsThiocyanatesJournal ArticleResearch Support, Non-U.S. Gov't

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Pierre-Yves Renard, Hervé Schwebel, Philippe Vayron, Ludovic Josien, Alain Valleix, Charles Mioskowski. 2002-07-02. Easy access to phosphonothioates.. https://doi.org/10.1002/1521-3765(20020703)8%3A13%3C2910%3A%3Aaid-chem2910%3E3.0.co%3B2-r

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2006

Direct reaction of oximes with crotylsarin, cyclosarin, or VX in vitro.

The direct reaction of seven pyridinium oximes with the organophosphorus compounds (OPCs) crotylsarin, cyclosarin, and VX was studied by spectrophotometry. This method allows to quantify different parameters: (a) the half-life times (t (1/2)) of the oxime-OPC reactions on the basis of the changes in the absorption at the zwitterion (betaine) peak maximum, (b) the first- and second-order rate constants (k (1), k (2)), and (c) the maximum reaction velocities (v (max)). The results of the study show that the reaction velocity of the nerve agents with any of the oximes investigated decreased in the order crotylsarin > cyclosarin > VX. The comparison of the reaction rates of the three therapeutically used oximes (2-PAM, obidoxime, HI 6) with the respective OPC gave the highest rate for crotylsarin and cyclosarin with obidoxime and to a similar degree with HI 6, while in the case of VX the most reactive oxime was HI 6. The reaction velocity of the nerve agents with the monopyridinium oxime 2-PAM was lower as compared to the bispyridinium oximes (obidoxime, HI 6). The results obtained with the two sarin analogues indicate that the direct reaction with 2-PAM, obidoxime, or HI 6 could be used for non-corrosive decontamination purposes, especially, if sensitive biological surfaces like skin, mucous membranes, or wounds are considered. However, in view of the concentrations of nerve agents and oximes, which could be expected during OPC poisoning in man, the maximum reaction velocities would not be high enough to contribute markedly to the detoxication of nerve agents in vivo.

Cholinesterase Inhibitors↗
PubMed2006

Synthesis of asymmetrical bispyridinium compounds bearing cyano-moiety and evaluation of their reactivation activity against tabun and paraoxon-inhibited acetylcholinesterase.

Three asymmetrical AChE reactivators with cyano-moiety and propane linker were synthesized using modification of currently known synthetic pathways. Their potency to reactivate AChE inhibited by nerve agent tabun and insecticide paraoxon was tested in vitro and compared to pralidoxime, HI-6, obidoxime, K027, and K048. According to the results, three compounds seem to be promising against paraoxon-inhibited AChE. Better results were obtained for bisquaternary substances at least with one oxime group in position four. None of tested substances was able to satisfactorily reactivate tabun-inhibited AChE at concentration applicable for in vivo experiments.

Cholinesterase Inhibitors↗