Fluoride-induced reactivation

Van der Schans, M.J., Polhuijs, M., Van Dijk, C., Degenhardt, C.E.A.M., Pleijsier, K., Langenberg, J.P., and Benschop, H.P. (2004). Retrospective detection of exposure to nerve agents analysis of phosphofluoridates originating from fluoride-induced reactivation of phosphylated BuChE. Arch. Toxicol., 78, 508-524. 

De Jong L.P., Van Dijk C. (1984). Formation of soman (1,2,2-trimethylpropyl methylphosphonofluoridate) via fluoride-induced reactivation of soman-inhibited aliesterase in rat plasma. Biochem. Pharmacol. 33 663-9. 

Retrospective detection of exposure to nerve agents analysis of phosphofluoridates originating from fluoride-induced reactivation of phos-phylated BuChE. Arch Toxicol, 78, 508-524. 

Analytical procedures applied to diagnosis and retrospective verification of exposure to OP include (Worek et al., 2005) (i) biochemical determination of ChE activity (ii) identification of imbound OP (iii) identification of decomposition products (iv) fluoride-induced reactivation of inhibited ChE, followed by analysis of the inhibitor and (v) analysis of phosphyl-protein-adducts after tryptic digestion of the protein. The last procedure is regarded to be the most specific and sensitive, but it has the drawback of being strongly dependent on the analysis of butyrylcholinesterase (BChE), the most abim-dant plasma serine esterase with a half-life of about 16 days. 

The reactive indolo-2,3-quinodimethanes are generated in situ generally from N-protected 2,3-disubstituted indoles (514,515). Generation of reactive indolo-2,3-quinodimethanes was achieved by fluoride-induced, 1,4-elimination of silylated indolyl ammonium salts, and was applied in the synthesis of substituted tetrahydrocarbazoles (516). Subsequently, the iodide-induced 1,4-elimination of ]V-benzoyl-2,3-bis(bromomethyl)indole (534) methodology was developed for the synthesis of reactive indolo-2,3-quinodimethanes and was applied for the first time in the synthesis of substituted carbazoles (e.g., 536) (517) (Scheme 5.14). 

Iodomethyltrimethylsilane has been used previously for this reaction (9, 444-445), but the tin reagent (1) is at least 600 times more reactive than the silicon reagent. Furthermore, fluoride-induced desulfonylstannylation is much faster than desulfonylsilylation, probably because a C-Sn bond is weaker than a C-Si bond. 

Azabutadiene systems, as more or less formal carbonyl derivatives, have been used for [4 + 2] cycloaddition reactions. The fluoride-induced stereoselective transformation of (144) to the polycyclic steroid-like system (145), obviously proceeding via the corresponding reactive aza-o-quinodimethane (Scheme 67), shows the synthetic utility of such heterodienes. 

Ito and coworkers developed a mild and efficient procedure for generating o-quinodimethanes" as reactive intermediates in [4 -I- 2] cycloadditions. The key step in the sequence, illustrated here by the synthesis of Estrone methyl ether (146 Scheme 53) involves a fluoride-induced fragmentation of the o-[a-(trimethylsilyl)alkyl]benzyltrimethylammonium iodide (144) to give the o-quinodimethane (145), which underwent stereoselective intramolecular [4 + 2] cycloaddition to give the desired tetracyclic framework in (146). The entire process was conducted at room temperature. The annulation reaction is not limited to intramolecular cycloadditions intermolecular versions of the reaction proceed equally well. 

Bromo-2-trimethylsilylcyclopropene underwent addition to 2-methoxyfuran. After hydrolysis and oxidation, the cycloadduct 8a underwent fluoride-induced elimination to form a benzo-cyclopropcne-2,5-quinone 9a as a reactive intermediate which was trapped with furan. The adducts 10a and 11a were isolated with a combined yield of 64%. An analogous sequence gave cyclopropa[/)]naphtho-2.7-quinone 9b isolated as mixture of furan adducts 10b and 11b (74%). 3 ... 

Cesium fluoride induced desilylation of immonium salts provides reactive azomethine yields, which are capable of 1,3-dipolar addition to many a, 8-unsaturated compounds to form heterocycles. Examples utilizing... 

Interest in 2-aza-1, 3-dienes with respect to their Diels-Alder reactivity is considerable, and thus these compounds have been widely studied. Notable research has included their syntheses by caesium fluoride-induced protiodesilylation of -(1-trImethy1-... 

Addition of PhMc2SiLi to aldehydes and subsequent 0-sulfo-nylation of the generated alkoxides with /7-toluenesulfonyl chloride affords a-silyl tosylates in good yields. Conversion of these intermediates into a-silyl selenocyanates followed by fluoride-induced cyanide elimination reaction permitted the synthesis and study of reactivity of previously unknown selenoaldehydes (eq A) ... 

In another study, oscillating rheometry was used to examine the effect of adding various simple metal salts to glass-ionomer cements (Crisp, Merson Wilson, 1980). It was found that cement formation for certain glasses which react only slowly with poly(acrylic acid) could be accelerated significantly by certain metal salts, mainly fluorides such as stannous fluoride and zinc fluoride. Some non-reactive glasses could be induced to set by the addition of such compounds. 

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