HMBC key correlation in structural elucidation of natural compounds.

GARCÍA MANUELA; VIVIANA NICOTRA

Alta Gracia

Congreso; Magnetic Resonance in a Cordubensis Perspective: New developments in NMR; 2011

Facultad de Matemática, Astronomía y Física, UNC

Sesquiterpene esters, based on dihydro-β-agarofuran [5,11-epoxy-5 β,10α-eudesm-4(14)-ene] skeleton, are chemotaxonomic indicators of the Celastraceae Family,1 and have received much attention in medicinal chemistry due to their wide range of biological activity, e.g., insecticidal, cytotoxic, anti-inflammatory, multidrug resistance (MDR) reversal, immunosuppressive, antiviral, anti-HIV, and anti-HSV.2 As part of a research program on biologically active metabolites from Celastraceae Family,3 Schaefferia argentinensis species was studied. Repeated chromatography on sephadex LH-20, preparative HPLC, and preparative TLC of the ethanolic extract yielded, in addition to the two known metabolites, eight new sesquiterpenes. This report aims at showing the application of solution NMR techniques to solve structural determination. The analysis of NMR spectral data indicate that these compounds contain a skeleton based on 15 carbons, i.e.: three methyl carbons; three methylene carbons; five methine carbons; and four quaternary carbons. These data also suggest that it is a 1,4,6,8,9,15-hexasubstituted-β-dihydroagarofuran skeleton (Fig. 1).4 All metabolites isolated have the same substituents such as hydroxyl or keto groups as well as acetyl, benzoyl and cinamoyl esters. The full and unambiguous proton and carbon NMR assignments for ten compounds were made using a combination of 1D and 2D NMR experiments. The only difference found between the compounds was the position and orientation of their substituents. The locations of the hydroxy and ester functions can be determined on the basis of 1H-13C long-range correlations (HMBC experiments). These positions were established by the key cross-correlation peaks observed for carbinyl protons of the β-dihydroagarofuran skeleton with carbonyl carbons of the substituents. The orientations of H-1, H-6, H-8 and H-9 were determined by analysis of the coupling constants and NOESY experiments. Although the structural diversity in this family of compounds is not particularly wide, a minimal variation in the type of substituent and the relative stereochemistry of each carbon in the molecule results in considerable changes in biological activity. In the current work, HMBC experiment has proven a key tool which provides valuable information on the structural elucidation of a family of naturally occurring compounds.