On the conformations of halichlorine and the pinnaic acids

Nitrogen inversion as a possible determinant of biological profile

Dirk Trauner, David G. Churchill, Samuel J. Danisliefsky

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)2344-2351
Number of pages8
JournalHelvetica Chimica Acta
Volume83
Issue number9
DOIs
StatePublished - 2000

Fingerprint

Quinolizidines
determinants
Conformations
Nitrogen
inversions
nitrogen
acids
alkaloids
Acids
rings
homology
profiles
closures
Alkaloids
Vascular Cell Adhesion Molecule-1
Structure-Activity Relationship
nuclear magnetic resonance
synthesis
Nuclear magnetic resonance
pinnaic acid

ASJC Scopus subject areas

  • Catalysis
  • Biochemistry
  • Drug Discovery
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

On the conformations of halichlorine and the pinnaic acids : Nitrogen inversion as a possible determinant of biological profile. / Trauner, Dirk; Churchill, David G.; Danisliefsky, Samuel J.

In: Helvetica Chimica Acta, Vol. 83, No. 9, 2000, p. 2344-2351.

Research output: Contribution to journalArticle

Trauner, Dirk ; Churchill, David G. ; Danisliefsky, Samuel J. / On the conformations of halichlorine and the pinnaic acids : Nitrogen inversion as a possible determinant of biological profile. In: Helvetica Chimica Acta. 2000 ; Vol. 83, No. 9. pp. 2344-2351.
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