Discovery of Staircase Chirality through the Design of Unnatural Amino Acid Derivatives.

Abstract

Chirality has garnered significant attention in the scientific community since its discovery by Louis Pasteur over a century ago. It has been showing a profound impact on chemical, biomedical, and materials sciences. Significant progress has been made in controlling molecular chirality, as evidenced by the several Nobel Prizes in chemistry awarded in this area, particularly for advancements in the asymmetric catalytic synthesis of molecules with central and axial chirality. However, the exploration of new types of chirality has been largely stagnant for more than half a century, likely due to the complexity and challenges inherent in this field. In this work, we present the discovery of a novel type of chirality-staircase chirality as inspired by the design and synthesis of unnatural amino acid derivatives. The architecture of staircase chirality is characterized by 2 symmetrical phenyl rings anchored by a naphthyl pier, with the rings asymmetrically displaced due to the influence of chiral auxiliaries at their para positions. This unique staircase chiral framework has been thoroughly characterized using spectroscopic techniques, with its absolute configuration definitively confirmed by x-ray diffraction analysis. Remarkably, one of the staircase molecules exhibits 4 distinct types of chirality: central, orientational, turbo, and staircase chirality, a combination that has not been previously documented in the literature. Computational studies using density functional theory (DFT) calculations were conducted to analyze the relative energies of individual staircase isomers, and the results are in agreement with our experimental findings. We believe that this discovery will open up a new research frontier in asymmetric synthesis and catalysis, with the potential to make a substantial impact on the fields of chemistry, medicine, and materials science.