From Relative to Absolute Stereochemistry of Secondary Metabolites: Applications in Plant Chemistry

Abstract

Structural elucidation of specialized metabolites or natural plant products, especially the stereochemical features of chiral bioactive metabolites, is the most important stage for all investigations in pharmacognosy and phytochemistry. Numerous methods have been established to solve the absolute configuration of natural products, including direct methods such as X-ray diffraction, chiroptical spectroscopy, stereo-controlled partial or total organic synthesis, and chemical correlation by simple organic reactions for derivatization, as well as indirect methods using a standard chiral compound or a derivatizing agent with known absolute configuration, for example, nuclear magnetic resonance by utilization of anisotropic effects of chiral agents. Once the relative configuration of a natural product is resolved, the absolute stereochemistry can be determined with the assistance of chiroptical spectroscopies supported by quantum mechanical-NMR prediction of chemical shifts, scalar coupling constants and simulation of optical rotatory dispersion, in addition to electronic and vibrational circular dichroism spectra. This review summarizes the most practical methods employed in the assignment of absolute stereochemistry of natural plant products with selected examples focused on multichiral center bioactive small molecules from the mega-diverse Brazilian and Mexican flora.