Deconstructing cytisine : The syntheses of (±)-cyfusine and (±)-cyclopropylcyfusine, fused ring analogs of cytisine

Daniel YOHANNES; Kristen PROCKO; Lorraine A LEBEL; Carol B FOX; Brian T O'NEILL

doi:10.1016/j.bmcl.2008.02.078

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Deconstructing cytisine : The syntheses of (±)-cyfusine and (±)-cyclopropylcyfusine, fused ring analogs of cytisine

Journal article

Peer reviewed

Deconstructing cytisine : The syntheses of (±)-cyfusine and (±)-cyclopropylcyfusine, fused ring analogs of cytisine

Daniel YOHANNES, Kristen PROCKO, Lorraine A LEBEL, Carol B FOX and Brian T O'NEILL

Bioorganic & medicinal chemistry letters, Vol.18(7), pp.2316-2319

2008

DOI: 10.1016/j.bmcl.2008.02.078

PMID: 18356044

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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.

Neuropharmacology

Biological and medical sciences

Cholinergic system

Medical sciences

Neurotransmitters. Neurotransmission. Receptors

Pharmacology. Drug treatments

Details

Title: Subtitle: Deconstructing cytisine : The syntheses of (±)-cyfusine and (±)-cyclopropylcyfusine, fused ring analogs of cytisine
Creators: Daniel YOHANNES - Pfizer Global Research and Development, Groton Laboratories, Eastern Point Road, Groton, CT 06340, United States
Kristen PROCKO - Pfizer Global Research and Development, Groton Laboratories, Eastern Point Road, Groton, CT 06340, United States
Lorraine A LEBEL - Pfizer Global Research and Development, Groton Laboratories, Eastern Point Road, Groton, CT 06340, United States
Carol B FOX - Pfizer Global Research and Development, Groton Laboratories, Eastern Point Road, Groton, CT 06340, United States
Brian T O'NEILL - Pfizer Global Research and Development, Groton Laboratories, Eastern Point Road, Groton, CT 06340, United States
Resource Type: Journal article
Publication Details: Bioorganic & medicinal chemistry letters, Vol.18(7), pp.2316-2319
DOI: 10.1016/j.bmcl.2008.02.078
PMID: 18356044
NLM abbreviation: Bioorg Med Chem Lett
ISSN: 0960-894X
eISSN: 1464-3405
Publisher: Elsevier
Language: English
Date published: 2008
Academic Unit: Endocrinology and Metabolism; Internal Medicine
Record Identifier: 9984094564502771

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