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On the Conformations of Halichlorine and the Pinnaic Acids: Nitrogen Inversion as a Possible Determinant of Biological Profile
Author(s) -
Trauner Dirk,
Churchill David G.,
Danishefsky Samuel J.
Publication year - 2000
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/1522-2675(20000906)83:9<2344::aid-hlca2344>3.0.co;2-2
Subject(s) - chemistry , quinolizidine , stereochemistry , nitrogen inversion , ring (chemistry) , nitrogen , alkaloid , organic chemistry
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 cPLA 2 , 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.