Stereochemistry of complex natural compounds by vibrational optical activity: acetogenins

Abstract

Determining the absolute configuration of chiral molecules is one of the mostchallenging tasks in natural product chemistry due to the structural complexity of secondarymetabolites containing multiple chiral centers. Among the techniques available to assess theirstereochemical properties, chiroptical spectroscopy, which arises from differential interactionof chiral molecules with circularly polarized radiation, is a powerful alternative. OpticalRotation, Optical Rotatory Dispersion, and Electronic Circular Dichroism are chiropticalmethods applied in the UV-visible spectral region. Vibrational Circular Dichroism and RamanOptical activity, on the other hand, are applied in the infrared region and are commonly referredto as Vibrational Optical Activity (VOA). In this project, we focus on the use of VOAtechniques to determine the relative (RC) and absolute (AC) configurations of severalacetogenins isolated from Annona mucosa (Annonaceae). These secondary metabolites presenta broad spectrum of biological activities, including potent pesticide activity, making thempromising candidates as natural insecticides against agricultural plagues in Brazil. However, itis extremely important to determine the exact spatial arrangement of their atoms. Moststereochemical data found in the literature for acetogenins are incomplete, and based primarilyon empirical 1H e 13C NMR analysis. Therefore, this project aims, through the combination oftheoretical and experimental spectroscopic data, to establish definitely the AC of acetogeninsdirectly in solution. The spectral signatures to be identified in this project will be useful in futurestudies of other molecules from the same class. (AU)