title: DFT 1H-1H coupling constants in the conformational analysis and stereoisomeric differentiation of 6-heptenyl-2H-pyran-2-ones: configurational reassignment of synargentolide A.
abstract: Density functional theory (DFT) (1) H-(1) H NMR coupling constant calculations, including solvation parameters with the polarizable continuum model B3LYP/DGDZVP basis set together with the experimental values measured by spectral simulation, were used to predict the configuration of hydroxylated 6-heptenyl-5,6-dihydro-2H-pyran-2-ones 1, 2, 4, and 7, allowing epimer differentiation. Modeling of these flexible compounds requires the inclusion of solvation models that account for stabilizing interactions derived from intramolecular and intermolecular hydrogen bonds, in contrast with peracetylated derivatives (3, 5, and 6) in which the solvation consideration can be omitted. Using this DFT NMR integrated approach as well as spectral simulation, the configurational reassignment of synargentolide A (8) was accomplished by calculations in the gas phase among four possible diastereoisomers (8-11). Calculated (3) JH,H values established its configuration as 6R-[4'S,5'S,6'S-(triacetyloxy)-2E-heptenyl]-5,6-dihydro-2H-pyran-2-one (8), in contrast with the incorrect 6R,4'R,5'R,6'R-diastereoisomer previously proposed by synthesis (12). Application of this approach increases the probability for successful enantiospecific total syntheses of flexible compounds with multiple chiral centers.
authors.affiliation: Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, Ciudad Universitaria, Mexico City, 04510, DF, Mexico.
authors.forename: Francisco
authors.initials: F
authors.lastname: Juárez-González
authors.forename: Gloria Alejandra
authors.initials: GA
authors.lastname: Suárez-Ortiz
authors.forename: Mabel
authors.initials: M
authors.lastname: Fragoso-Serrano
authors.forename: Carlos M
authors.initials: CM
authors.lastname: Cerda-García-Rojas
authors.forename: Rogelio
authors.initials: R
authors.lastname: Pereda-Miranda
mesh_terms: D008968:Molecular Conformation; D066244:Proton Magnetic Resonance Spectroscopy; D011714:Pyrans / Q000737:chemistry*; D011753:Pyrones / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization; D013237:Stereoisomerism
chemical_list: D011714:Pyrans; D011753:Pyrones; C000602530:synargentolide A
keywords: 1H-1H coupling constants; NMR spectroscopy; configuration; conformational analysis; density functional calculations; spectral simulation; synargentolide A