Enantiospecific synthesis of annulated nicotine analogues from D-glutamic acid. 7-Azabicyclo[2.2.1]heptano[2.3-c]pyridines

J R Lennox; S C Turner; H Rapoport

doi:10.1021/jo010534y

Enantiospecific synthesis of annulated nicotine analogues from D-glutamic acid. 7-Azabicyclo[2.2.1]heptano[2.3-c]pyridines

J Org Chem. 2001 Oct 19;66(21):7078-83. doi: 10.1021/jo010534y.

Authors

J R Lennox¹, S C Turner, H Rapoport

Affiliation

¹ Department of Chemistry, University of California, Berkeley, California 94720, USA.

PMID: 11597233
DOI: 10.1021/jo010534y

Abstract

The conformationally restricted nicotinoid (1S,4S)-7-methyl-7-azabicyclo[2.2.1]heptano[2,3-c]pyridine dihydrochloride has been prepared enantiospecifically from D-glutamic acid. The method involved a lithium cis-2,6-dimethylpiperidide-mediated intramolecular anionic cyclization of (2S,5R)-N-(tert-butyloxycarbonyl)-5-[3-(4-N-chloropyridinyl]proline methyl ester in tandem with a standard decarboxylation sequence. Reductive amination afforded the desired N-methylated [2.2.1]bicyclonicotinoid. Cyclization of the corresponding iodopyridinylproline methyl ester, obtained via ultrasound-facilitated chloro-iodo exchange, was also effected.

MeSH terms

Aza Compounds / chemical synthesis
Aza Compounds / chemistry
Bridged Bicyclo Compounds, Heterocyclic / chemical synthesis
Bridged Bicyclo Compounds, Heterocyclic / chemistry
Drug Design
Glutamic Acid / chemistry*
Nicotine / analogs & derivatives*
Nicotine / chemical synthesis
Nicotine / chemistry
Nicotinic Agonists
Nicotinic Antagonists
Pyridines / chemical synthesis
Pyridines / chemistry
Stereoisomerism

Substances

Aza Compounds
Bridged Bicyclo Compounds, Heterocyclic
Nicotinic Agonists
Nicotinic Antagonists
Pyridines
Glutamic Acid
Nicotine