Conformationally restricted leukotriene antagonists. Modeling and assignment of structure of [(Octahydro-2-oxo-7-tetra-decylidene-2H-1-benzopyran-8-yl)thio]acetic acids

Abstract

The proton NMR spectrum of the conformationally restricted, leukotriene antagonist [(octahydro-2-oxo-7-tetradecylidene-2H-1-benzopyran-8-yl)thio]acetic acid ($\text{3a}$) did not support a chair-chair conformation for the bicyclic ring system as is usually expected. Molecular mechanics and semi-empirical molecular orbital calculations, on the model compounds $\text{3b}$ and $\text{4b}$, indicated that $\text{3a}$ exists in a chair-boat rather than a chair-chair form. The findings of this computational study were confirmed by a subsequent x-ray analysis.