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Conformational analysis of phorboxazole bis‐oxazole oxane fragment analogs by NMR spectroscopy and molecular modeling simulations
Author(s) -
Fontana Carolina,
Incerti Marcelo,
Moyna Guillermo,
Manta Eduardo
Publication year - 2008
Publication title -
magnetic resonance in chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.483
H-Index - 72
eISSN - 1097-458X
pISSN - 0749-1581
DOI - 10.1002/mrc.2120
Subject(s) - chemistry , oxazole , moiety , two dimensional nuclear magnetic resonance spectroscopy , stereochemistry , conformational isomerism , nuclear magnetic resonance spectroscopy , molecular model , heteronuclear single quantum coherence spectroscopy , molecule , computational chemistry , crystallography , organic chemistry
Abstract We present a detailed conformational study of a simplified synthetic analog of the bis‐oxazole oxane fragment found in the cytostatic agents phorboxazole A and B based on results from NMR spectroscopy and molecular modeling simulations. Complete 1 H and 13 C resonance assignments for the bis‐oxazole oxane system were carried out through the use of COSY, HSQC, HMBC, TOCSY, and HSQC‐TOCSY experiments, and its conformational preferences in solution were investigated by analysis of 3 J HH coupling constants and NOE enhancements obtained from 1D and 2D NOESY experiments. In order to solve inconsistencies from our preliminary structural studies, simulated annealing studies were performed to thoroughly sample the phase space available to the molecule. Our results reveal that the six‐membered oxane ring, which constitutes the most important moiety regarding the three‐dimensional (3D) structure and flexibility of the analog, exists in rapid equilibrium between its two accessible chair conformers in an approximate ratio of 70:30. The information gathered from these studies will be of critical importance in our efforts to prepare novel compounds with phorboxazole‐like structure and activity. Copyright © 2008 John Wiley & Sons, Ltd.