- Restricted rotations of chemical bonds can lead to the
presence of persistent conformational chirality in molecules
10 lacking stereocenters. We report the development of first-ofa-
kind predictive rules that enable identification of
conformational chirality and prediction of racemization
barriers in the diarylether heptanoid (DAEH) natural
products that do not possess stereocenters. These empirical
15 rules-of-thumb are based on quantum mechanical
computations (SCS-MP2/∞//B3LYP/6-31G*/PCM) of
racemization barriers of four representative DAEHs.
Specifically, the local symmetry of ring B and the E/Z
configuration of the vinylogous acid/ester are critical in
20 determining conformational chirality in the DAEH natural
Molecular chirality is of paramount importance to chemistry,
biology, and medicine. Small molecules that are chiral by virtue
of restricted rotations (atropisomerism), or conformational
25 chirality, are an underdeveloped territory with the potential for
new developments of chiral ligands, medicinal compounds,
catalysts, and materials. At present, there are no known methods
to predict the presence of persistent conformational chirality in
these compounds based solely on their molecular architecture
30 without resorting to total synthesis. Specifically in this report,
we have developed predictive rules-of-thumb for the chiral
properties of all members in a family of cyclophane natural
products called the diarylether heptanoids (DAEHs).
Additionally, we elucidate the atomistic and energetic details
35 related to the racemizations.
- Pattawong, O., Salih, M. Q., Rosson, N. T., Beaudry, C. M., & Cheong, P. H. Y. (2014). The nature of persistent conformational chirality, racemization mechanisms, and predictions in diarylether heptanoid cyclophane natural products. Organic & Biomolecular Chemistry, 12(20), 3303-3309. doi:10.1039/c3ob42550a
- This is an author's peer-reviewed final manuscript, as accepted by the publisher.