Design and Synthesis of anα,α-Difluorophosphinate Hapten for Antibody-Catalyzed Hydrolysis of Organophosphorus Nerve Agents

Abstract

In a new approach to the safe neutralization of organophosphorus chemical weapons, we designed a hapten to elicit catalytic antibodies with phosphatase activity. Here we report the synthesis of this alpha,alpha-difluorophosphinate hapten 6. Various methods for the introduction of the key alpha,alpha-difluoromethyl feature into the phosphinate hapten are discussed. The best results were obtained with the electrophilic gem-difluorinating agent N-fluorobenzenesulfonimide.

Application of N-halo reagents in organic synthesis

“…An important application of N-fluoro reagents is fluorination of activated methylene [225][226][227][228][229][230][231][232][233][234][235][236][237] …”

An approach to (4-fluoroalkyl-1-alkyl-1H-pyrazol-3-yl)methylamines

“…Reaction of aldehydes 5, as well as the corresponding carboxylic acids or alcohols with sulfur-containing fluorinating reagents could be a method of choice to achieve this. It should be noted that such fluorinations in the presence of phtalimide moiety was described in the literature, however, it did not involve pyrazole derivatives [14][15][16][17][18][19][20][21]. It was found that fluorination of 5a with diethylaminosulfur trifluoride (DAST) proceeded smoothly and led to formation of the corresponding difluoromethyl derivative 14a in 82% yield (Scheme 3).…”

Biomaterials for Mediation of Chemical and Biological Warfare Agents

“…Interesting results have been obtained on the development of catalytic monoclonal antibodies and may lead to efficient treatments (45)(46)(47). The ability of nerve agent-degrading enzymes administered exogeneously to detoxify nerve agents and OP pesticides in vivo has been demonstrated in the particular cases of human paraoxonase (PON) and the bacterial phosphotriesterase from Pseudonomas diminuta using mammalian models (45).…”