Two Step Synthesis of a Non-symmetric Acetylcholinesterase Reactivator 英文参考文献.docVIP

Molecules 2007, 12, 1755-1761 molecules ISSN 1420-3049 ? 2007 by MDPI /molecules Communication Two Step Synthesis of a Non-symmetric Acetylcholinesterase Reactivator Kamil Musilek 1,2, Kamil Kuca 1,3*, Vlastimil Dohnal 1,4, Daniel Jun 1,3, Jan Marek 2 and Vit Koleckar 3 1 Department of Toxicology, Faculty of Military Health Sciences, Trebesska 1575, 500 01 Hradec Kralove, Czech Republic 2 Faculty of Pharmacy in Hradec Kralove, Charles University in Prague, Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic 3 Center of Advanced Studies, Faculty of Military Health Sciences, Trebesska 1575, 500 01 Hradec Kralove, Czech Republic 4 Department of Food Technology, Mendel University of Agriculture and Forestry Brno, Zemedelska 1, 613 00 Brno, Czech Republic * Author to whom correspondence should be addressed; E-mail: kucakam@pmfhk.cz Received: 25 June 2007; in revised form: 1 August 2007 / Accepted: 6 August 2007 / Published: 7 August 2007 Abstract: The newly developed and very promising acetylcholinesterase reactivator (E)-1- (2-hydroxyiminomethylpyridinium)-4-(4-hydroxyiminomethylpyridinium)-but-2-ene dibromide was prepared using two different pathways via a two-step synthesis involving the appropriate (E)-1-(4-bromobut-2-enyl)-2- or 4-hydroxyiminomethyl-pyridinium bromides. Afterwards, purities and yields of the desired product prepared by both routes were compared. Finally, its potency to reactivate several nerve agent-inhibited acetylcholinesterases was tested. Keywords: Quaternary; alkylation; acetylcholinesterase; reactivator; oxime; nerve agents  Molecules 2007, 12 1756 Introduction Organophosphorus nerve agents are probably the most toxic compounds prepared by the chemical industry. Their production began in Germany prior to World War II (the organophosphate Tabun, 1936). Since World War II, many other organophosphorus derivatives have been considered as more or less toxic compounds for