First total synthesis of (+/-)-3-hydroxy-11-norcytisine: structure confirmation and biological characterization

Daniel Yohannes; Camilla P Hansen; Srinivasa Rao Akireddy; Terry A Hauser; Melanie N Kiser; Nicholas J Gurnon; Cynthia S Day; Balwinder Bhatti; William S Caldwell

doi:10.1021/ol802145b

First total synthesis of (+/-)-3-hydroxy-11-norcytisine: structure confirmation and biological characterization

Org Lett. 2008 Dec 4;10(23):5353-6. doi: 10.1021/ol802145b.

Authors

Daniel Yohannes¹, Camilla P Hansen, Srinivasa Rao Akireddy, Terry A Hauser, Melanie N Kiser, Nicholas J Gurnon, Cynthia S Day, Balwinder Bhatti, William S Caldwell

Affiliation

¹ Targacept, Inc., 200 East First Street, Suite 300, Winston-Salem, North Carolina 27101, USA. [email protected]

PMID: 19007172
DOI: 10.1021/ol802145b

Abstract

The first total synthesis of the natural product 3-hydroxy-11-norcytisine (1), structurally related to cytisine (2), a benchmark ligand at neuronal nicotinic acetylcholine receptors (NNRs), has been achieved. The synthesis permits the unambiguous confirmation of the structure originally proposed for 1 and has enabled initial biological characterization of 1 and its related compounds against NNRs.

MeSH terms

Alkaloids / chemical synthesis*
Alkaloids / chemistry
Alkaloids / metabolism*
Animals
Azocines / chemical synthesis
Azocines / chemistry
Azocines / metabolism
Magnetic Resonance Spectroscopy
Quinolizines / chemical synthesis
Quinolizines / chemistry
Quinolizines / metabolism
Rats
Receptors, Nicotinic / metabolism
alpha7 Nicotinic Acetylcholine Receptor

Substances

Alkaloids
Azocines
Chrna7 protein, rat
Quinolizines
Receptors, Nicotinic
alpha7 Nicotinic Acetylcholine Receptor
nicotinic receptor alpha4beta2
cytisine