Conformational analysis of spiro-epoxides by principal component analysis of molecular dynamics trajectories

A new procedure for full conformational analyses comprising the statistical analysis of molecular dynamics trajectories was developed and applied. This method included a coordinate space for sampling using molecular dynamics simulations, reduction of dimensionality using tensor decomposition tools, determination of probability distributions in a reduced space, and finally the search for all of the strict extrema points of probability distributions. These extracted extrema points formed an initial guess for geometry optimization and clustering of conformers. A complete conformational space of 1-oxaspiro[2,5]octane and its cis- and trans-4-, 5- and 6-methyl substituted derivatives was also determined. In each case, eight conformers were found with two chair-like conformers predominant at room temperature. It was found that chair-like conformers with an epoxide ring oxygen atom in the pseudo-axial position had less strain, as well as all of their conformers with the methyl substituent in an equatorial position on a cyclohexane moiety.