Pure and Applied Chemistry

Abstract: The stereochemical study of flexible stereogenic carbon chains, such as those of many novel natural products, is a particularly challenging task. Recent applications of our group on the so-called "J-based approach", a methodology relying on a detailed analysis of homonuclear (H-H) and heteronuclear (C-H) ^2,3J couplings, include the study of the sphinxolide family of antitumor macrolides, a group of molecules characterized by a flexible macrocyclic framework bearing a number of oxygenated and methylated undetermined stereocenters, and of ascaulitoxin, a nitrogen-containing phytotoxin with herbicidal activity produced by a phytopathogenic fungus. An extension of the original procedure, relying on a Hartree-Fock (HF) ab initio calculation of conformational equilibrium and an estimate of the Boltzmann averaged ^2,3JHH and ^2,3JCH couplings, has been applied to the stereochemical study of sapinofuranone A, where the conformational equilibrium among existing rotamers had initially led to controversial results. ¹³C NMR chemical shifts are additional useful parameters in the study of complex organic molecules. Along these lines, we have lately proposed the use of Hartree–Fock gauge including atomic orbitals (GIAO) calculated ¹³C NMR chemical shift values as a supporting tool for the validation of the structure of new natural products and the determination of the relative stereochemistry of diastereomeric flexible compounds that are characterized by multiple conformer equilibria.