np5b00511_si_001.pdf (13.52 MB)
Advanced Structural Determination of Diterpene Esters Using Molecular Modeling and NMR Spectroscopy
journal contributionposted on 2015-10-23, 00:00 authored by Louis-Félix Nothias-Scaglia, Jean-François Gallard, Vincent Dumontet, Fanny Roussi, Jean Costa, Bogdan I. Iorga, Julien Paolini, Marc Litaudon
Three new jatrophane esters (1–3) were isolated from Euphorbia amygdaloides ssp. semiperfoliata, including an unprecedented macrocyclic jatrophane ester bearing a hemiketal substructure, named jatrohemiketal (3). The chemical structures of compounds 1–3 and their relative configurations were determined by spectroscopic analysis. The absolute configuration of compound 3 was determined unambiguously through an original strategy combining NMR spectroscopy and molecular modeling. Conformational search calculations were performed for the four possible diastereomers 3a–3d differing in their C-6 and C-9 stereocenters, and the lowest energy conformer was used as input structure for geometry optimization. The prediction of NMR parameters (1H and 13C chemical shifts and 1H–1H coupling constants) by density functional theory (DFT) calculations allowed identifying the most plausible diastereomer. Finally, the stereostructure of 3 was solved by comparison of the structural features obtained by molecular modeling for 3a–3d with NMR-derived data (the values of dihedral angles deduced from the vicinal proton–proton coupling constants (3JHH) and interproton distances determined by ROESY). The methodology described herein provides an efficient way to solve or confirm structural elucidation of new macrocyclic diterpene esters, in particular when no crystal structure is available.
13 C chemical shiftscompound 3Conformational search calculationsgeometry optimizationEuphorbia amygdaloides sspMolecular Modelingmacrocyclic diterpene estersenergy conformerdihedral anglescrystal structuremacrocyclic jatrophane esterinput structureDiterpene Estersmodelingconfigurationdiastereomers 3hemiketal substructureinterproton distanceschemical structuresDFTAdvanced Structural DeterminationconstantJHHNMR SpectroscopyThreeROESYNMR spectroscopyspectroscopic analysis