Total Synthesis of (-)-Cocaine and (-)-Ferruginine

Total synthesis of (-)-cocaine and (-)ferruginine. Cheng G, Wang X, Zhu R, Shao C, Xu J, Hu Y.

Source Department of Chemistry, Tsinghua University, Beijing 100084, People's Republic of China.

Abstract Total synthesis of tropane alkaloids (-)-cocaine and (-)-ferruginine were accomplished in nine steps each and in 55% and 46% overall yields, respectively, starting from the known Betti base derivative (+)-(7aR,10R,12S)-10-(1H-benzotriazol-1-yl)-7a,8,9,10-tetrahydro-12phenyl-12H-naphtho[1,2-e]pyrrolo[2,1-b][1,3]oxazine. In this novel route, RCM reaction and 1,3-dipolar cycloaddition were employed as key steps for the enantioselective construction of tropane skeleton and the regioselective introduction of 3-bromo-2-isoxazoline ring as masked cis-2,3-disubstituents. To obtain the desired precursor (2S,5R)-2-allyl-5-vinylpyrrolidine for RCM reaction, we developed a general and practical method for the preparation of enantiopure cis-2,5-disubstituted pyrrolidines bearing alkene- and/or alkyne-containing substituents. We also offered two highly efficient pathways for the conversion of the 3-bromo2-isoxazoline ring into the desired cis-2,3-disubstituted groups in (-)-cocaine and (-)ferruginine. PMID: 21391709 [PubMed - indexed for MEDLINE]

Publication Types, MeSH Terms, Substances Publication Types 

Research Support, Non-U.S. Gov't

MeSH Terms           

Alkenes/chemistry Alkynes/chemistry Bicyclo Compounds, Heterocyclic/chemical synthesis* Bicyclo Compounds, Heterocyclic/metabolism Cocaine/chemical synthesis* Cocaine/metabolism Dopamine Uptake Inhibitors/antagonists & inhibitors Dopamine Uptake Inhibitors/metabolism Molecular Structure Nicotinic Agonists/chemical synthesis* Nicotinic Agonists/metabolism

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Pyrrolidines/chemical synthesis* Receptors, Dopamine/metabolism Receptors, Nicotinic/metabolism Stereoisomerism Vinyl Compounds/chemistry

Substances           

Alkenes Alkynes Bicyclo Compounds, Heterocyclic Dopamine Uptake Inhibitors Nicotinic Agonists Pyrrolidines Receptors, Dopamine Receptors, Nicotinic Vinyl Compounds ferruginine Cocaine

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