HMBC key correlation in structural elucidation of natural compounds

MANUELA GARCIA, V.NICOTRA, J.C. OBERTI

Alta Gracia

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

Facultad de Matem¨¢tica, Astronom¨ªa y F¨ªsica, UNC

 The sesquiterpene esters, based on the dihydro-¦Â-agarofuran [5,11-epoxy-5 ¦Â,10¦Á-eudesm-4(14)-ene] skeleton, are chemotaxonomic indicators of the Celastraceae Family,1 and they have received much attention from medicinal chemists due to their wide range of biological activities, e.g., insecticidal, cytotoxic, anti-inflammatory, multidrug resistance (MDR) reversal, immunosuppressive, antiviral, anti-HIV, and anti-HSV.2 As part of a program of research into 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 ethanol extract of the aerial parts of S.argentinensis yielded, in addition to the known two metabolites, eight new sesquiterpenes. This report aims to show the application of solution NMR techniques to solve structural determination. The analysis of NMR spectral data indicated that these compounds containing a skeleton based on 15 carbons: three methyl carbons, three methylene carbons, five methine carbons and four quaternary carbons. These data suggested it to have a 1,4,6,8,9,15-hexasubstituted-¦Â-dihydroagarofuran skeleton.4 (Figure 1) All metabolited isolated have the same substituyents 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 1D and 2D NMR experiments. The only difference between the compounds was the position and orientation of their substituents. The locations of the hydroxy and ester functions can be determinated on the basis of 1H-13C long-range correlations (HMBC experiments). These positions were stablished by the key cross-correlation peaks observed for carbinyl protons of the ¦Â-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  by NOESY experiments. Although the structural diversity in this family of compounds is not very wide, a minimal variation in the type of substituent and the relative stereochemistry of each carbon in the molecule, result in large changes in biological activity. In the current work HMBC experiment has proven a key tool that provides valuable information for the structural elucidation of a family of naturally occurring compounds. REFERENCES: Br¨¹ning, R.; Wagner, H. Phytochemistry. 1978, 17, 1821-1858. Gonz¨¢lez, A. G.;et.al. Bioorg. Med. Chem. 2000, 8, 1773-1778. Spivey, A. C.; Weston, M.; Woodhead, S. Chem. Soc. Rev. 2002, 31, 43-59. Gonz¨¢lez, A. G, et.al. Tetrahedron. 1993, 49, 697-702.