Abstract
A novel fused tricyclic analog (11) of cytisine has been prepared (coined 'cyfusine') and determined to have high affinity at neuronal nicotinic acetylcholine receptors. A [3+2] cycloaddition protocol permitted entry into a 3,4-differentially difunctionalized dihydropyrrole (7). The penultimate cyclization was accomplished using the modified Van Tamelen conditions developed in our earlier synthesis of (+/-)-cytisine. Sequential ring-forming reactions ([3+2] cycloaddition/cyclopropanation/pyridone cyclization) gives a unique cyclopropyl analog (16) possessing a skeleton isoatomic with that of cytisine.
MeSH terms
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Alkaloids / chemistry*
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Azocines / chemistry
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Cyclization
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Cyclopropanes / chemistry
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Heterocyclic Compounds, 3-Ring / chemistry*
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Models, Chemical
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Pyridones / chemical synthesis*
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Pyridones / chemistry
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Pyridones / metabolism
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Pyrroles / chemical synthesis*
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Pyrroles / chemistry
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Pyrroles / metabolism
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Quinolizines / chemistry
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Receptors, Nicotinic / chemistry*
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Receptors, Nicotinic / metabolism
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Stereoisomerism
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Structure-Activity Relationship
Substances
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Alkaloids
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Azocines
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Cyclopropanes
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Heterocyclic Compounds, 3-Ring
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Pyridones
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Pyrroles
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Quinolizines
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Receptors, Nicotinic
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pyrroline
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cytisine
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cyclopropane