On the conformations of halichlorine and the pinnaic acids: Nitrogen inversion as a possible determinant of biological profile Journal Article

  

Authors:	Trauner, D.; Churchill, D. G.; Danishefsky, S. J.
Article Title:	On the conformations of halichlorine and the pinnaic acids: Nitrogen inversion as a possible determinant of biological profile
Abstract:	Although the marine alkaloids halichlorine (1) and the pinnaic acids 2, which contain a quinolizidine ring system, exhibit considerable structural homology, they act upon different biological targets (VCAM-1 and cPLA2, respectively). Quinolizidines can exist as cisoid or transoid invertomers. In the recently reported total synthesis of (+)-halichlorine, it was determined by NMR that advanced intermediates 3 and 4, containing the spiroquinolizidine core, exhibit the transoid conformation, while the macrolactone-containing halichlorine has the cisoid conformation. We conclude that constraints imposed upon closure of the macrolactone ring force adoption of the cisoid conformation. The major conformational reorganization upon macrolactonization has implications for the design of pharmacophors and anticipated structure-activity relationships in their action on biological targets.
Keywords:	unclassified drug; vascular cell adhesion molecule 1; structure activity relation; pharmacophore; conformational transition; x ray crystallography; phospholipase a2; molecular model; proton nuclear magnetic resonance; lactone derivative; drug conformation; alkaloid; nuclear overhauser effect; article; halichlorine; pinnaic acid; quinolizidine derivative
Journal Title:	Helvetica Chimica Acta
Volume:	83
Issue:	9
ISSN:	0018-019X
Publisher:	Wiley V C H Verlag Gmbh
Date Published:	2000-09-06
Start Page:	2344
End Page:	2351
Language:	English
DOI:	10.1002/1522-2675(20000906)83:9<2344::aid-hlca2344>3.0.co;2-2
PROVIDER:	scopus
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-0033787008&partnerID=40&md5=fb64c15ca81c6b0dc20aa5da3a0b2e60
Notes:	Export Date: 18 November 2015 -- Source: Scopus

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