Open AccessNMR and molecular modeling study of active and inactive taxol analogues in aqueous and nonaqueous solution
Author(s) -
Howard J. Williams,
A. Ian Scott,
Reiner Dieden,
Charles S. Swindell,
Lisa Emily Chirlian,
Michelle Francl,
Julia M. Heerding,
Nancy E. Krauss
Publication year - 1994
Publication title -
canadian journal of chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.323
H-Index - 68
eISSN - 1480-3291
pISSN - 0008-4042
DOI - 10.1139/v94-038
Subject(s) - chemistry , aqueous solution , molecular model , chloroform , biological activity , two dimensional nuclear magnetic resonance spectroscopy , stereochemistry , side chain , proton nmr , nuclear magnetic resonance spectroscopy , coupling constant , combinatorial chemistry , molecule , computational chemistry , organic chemistry , in vitro , biochemistry , polymer , physics , particle physics
The conformations of the biologically active taxol analogs Taxotere®, 3R, 4R, and 4S, and the biologically inactive analog 3S were evaluated in CDCl 3 and DMSO–water solution using 1 H NMR coupling constant and NOESY data and molecular modeling. The solution structures of Taxotere® were very similar to those detected previously for taxol. The A-ring side chain conformations of analogs 3 and 4 could not be defined with the same precision as had been possible for taxol, but the conformational possibilities could be significantly limited by the data. Analogs 3R, 4R, and 4S (but not 3S) can mimic the dominant conformation of taxol in chloroform, but no logical relationship between biological activity and aqueous solution conformation could be detected.
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