Cocaine analogues, synthesis

Hardegger, E., and Ott, H. 1955. Konfiguration des cocains und derivate der ecgoninsaure. Helv ChimActa 38, 312-320. Hernandez, A., and Rapoport, H. 1994. Conformationally constrained analogues of anatoxin, chirospecific synthesis of s-trans carbonyl ring-fused analogues. J Org Chem 59, 1058-1066. 

Iso Y, Grajkowska E, Wroblewski JT et al (2006) Synthesis and structure-activity relationships of 3-[(2-methyl-1, 3-thiazol-4-yl)ethynyl]pyridine analogues as potent, noncompetitive metabotropic glutamate receptor subtype 5 antagonists search for cocaine medications. J Med Chem 49 1080-1100... 

Tamiz, A.P., Smith, M.P. and Kozikowski, A.P. (2000) Design, synthesis and biological evaluation of 7-azatricyclodecanes analogue of cocaine. Bioorg. Med. Chem. Lett. 10 297-300. 

Deutsch HM, Shi Q, Gruszecka-Kowalik E, et al. Synthesis and pharmacology of potential cocaine antagonists. 2. Structure-activity relationship studies of aromatic ring-substituted methylphenidate analogues. J Med Chem 1996 39 1201-1209. 

An elegant synthesis of oxygen analogues of cocaine is shown in Scheme 24. Further photochemical studies concern the formation of an oxetan in the well-studied series of 5-acyl-norbornenes, and the formation of oxetan from... 

Davies has further exploiled his previously reporied approach to (he tropanc skeleton related to cocaine based on the rhodium catalyzed decomposition of the vinyidiazomethane 81 in the presence of A/-Boc-pyrroIe (82) <01BMCL487>. Reduction of the non-conjugated double bond followed by A -deprotection and N-alkylation provided substrate 83 which was susceptible to conjugate addition of nucleophiles such as 84 in the presence of CuBr to afford 3-p-aryl tropanes which exhibited potent binding affinity for both the dopamine and serotonin transporters. Additionally, this author described the synthesis of various methyl heteroaryldiazoacetate analogues of 81, (me of which possessed an indole function, for use in catalytic asymmetric cyclopropanations . 

Cycloaddition of oxyallyl cations to N-methylpyrrole and furan leads to novel analogues of cocaine (Scheme 74). ° In a somewhat related synthesis the tropane skeleton has been prepared using bromo-ketone-iron carbonyl coupling to pyrroles (Scheme 75). ° ... 

Kim DI, Deutsch HM, Ye XC, Schweti MM. Synthesis and pharmacology of site-specific cocaine abuse treatment agents Restricted rotation analogues of methylphenidate. / Med Chem. 2007 50 2718-2731. 

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