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|Section2= |Section3= }} Methylecgonidine (anhydromethylecgonine; anhydroecgonine methyl ester) is a chemical intermediate derived from ecgonine or cocaine. Methylecgonidine is a pyrolysis product formed when crack cocaine is smoked, making this substance a useful biomarker to specifically test for use of crack cocaine, as opposed to powder cocaine which does not form methylecgonidine as a metabolite.〔 Scheidweiler KB, Plessinger MA, Shojaie J, Wood RW, Kwong TC. Pharmacokinetics and pharmacodynamics of methylecgonidine, a crack cocaine pyrolyzate. Journal of Pharmacology and Experimental Therapeutics. 2003 Dec;307(3):1179-87.〕 Methylecgonidine has a relatively short half-life of 18-21 minutes, after which it is metabolised to ecgonidine, meaning that the relative concentrations of the two compounds can be used to estimate how recently crack cocaine has been smoked. Methylecgonidine has been shown to be specifically more harmful to the body than other byproducts of cocaine; for example to the heart,〔(Pharmacokinetics and Pharmacodynamics of Methylecgonidine, a Crack Cocaine Pyrolyzate - Scheidweiler et al. 307 (3): 1179 Figure IG6 - Journal of Pharmacology And Experimental Therapeutics )〕 lungs〔British Journal of Pharmacology (- Abstract of article: Evidence for cocaine and methylecgonidine stimulation of M2 muscarinic receptors in cultured human embryonic lung cells )〕 & liver.〔(Studies on Hydrolytic and Oxidative Metabolic Pathways of Anhydroecgonine Methyl Ester (Methylecgonidine) Using Microsomal Preparations from Rat Organs (Chemical Research in Toxicology/ACS Publications) )〕 It is also used in scientific research for the manufacture of phenyltropane analogues such as Troparil, Dichloropane, Iometopane and CFT. Methylecgonidine could also theoretically be used to produce cocaine and so may be a controlled substance in some countries. ==Synthesis== (1) Hydrolysis,〔DeJong, A. W. K. Recl. Trav. Chim. 1937, 57, 186.〕 (2) dehydration,〔Matchett, J. R.; Levine, J. J. Am. Chem. Soc. 1941, 63, 2444.〕 and (3) esterification.〔 Bell, M. R.; Archer, S. J. Am. Chem. Soc. 1960, 82, 4642.〕 The scheme by Kline〔Kline, R. H., Jr.; Wright, J.; Fox, K. M.; Eldefrawi, M. E. J. Med.Chem. 1990, 33, 2024.〕 is based on the reaction of 2,4,6-cycloheptatriene-7-carboxylic acid with methylamine. This is a modified version of by Grundmann and Ottmann. In the accompanying patent these same authors react their Methylecgonidine with two equivalents of PhLi to form a 3° alcohol by "hard" addition to the ester and not "soft" Michael addition. However, the product is only 1/10th the potency of atropine. The methyl 2,4,6-cycloheptatriene-1-carboxylate can be made synthetically.〔http://www.chemsynthesis.com/base/chemical-structure-15475.html〕 Davies et al. synthesized R/S-Methylecgonidine by a tandem cyclopropanation/Cope rearrangement.〔Davies, H. M. L.; Saikali, E.; Young, W. B. J. Org. Chem. 1991, 56, 5696.〕〔Davies, H. M. L.; Young, W. B.; Smith, H. D. Tetrahedron Lett.1989, 30, 4653.〕 Thus, reaction of methyldiazobutenoate (2) with 5 equiv of N-((2-(TMS)ethoxy)carbonyl)pyrrole (1) in the presence of rhodium(II) hexanoate/hexane gave the ()-azabicyclic system R/S-8 in 62% yield. The unsubstituted double bond was selectively reduced using Wilkinson catalyst to provide N-protected anhydroecgonine methyl ester (R/S-4). Following deprotection of N8 nitrogen with TBAF and reductive methylation with formaldehyde and sodium cyanoborohydride, R/S-5 was obtained in overall good yield (Scheme 3). 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Methylecgonidine」の詳細全文を読む スポンサード リンク
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