Enantiospecific synthesis of annulated nicotine analogues from D-glutamic acid. 7-Azabicyclo[2.2.1]heptano[2.3-c]pyridines.
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.
Lennox
J R
JR
Department of Chemistry, University of California, Berkeley, California 94720, USA.
Turner
S C
SC
Rapoport
H
H
D001372:Aza Compounds / Q000138:chemical synthesis / Q000737:chemistry; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis / Q000737:chemistry; D015195:Drug Design; D018698:Glutamic Acid / Q000737:chemistry*; D009538:Nicotine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry; D013237:Stereoisomerism
D001372:Aza Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011725:Pyridines; D018698:Glutamic Acid; D009538:Nicotine