title: Vicinal 1H-1H NMR coupling constants from density functional theory as reliable tools for stereochemical analysis of highly flexible multichiral center molecules.
abstract: A protocol for stereochemical analysis, based on the systematic comparison between theoretical and experimental vicinal (1)H-(1)H NMR coupling constants, was developed and applied to a series of flexible compounds (1-8) derived from the 6-heptenyl-5,6-dihydro-2H-pyran-2-one framework. The method included a broad conformational search, followed by geometry optimization at the DFT B3LYP/DGDZVP level, calculation of the vibrational frequencies, thermochemical parameters, magnetic shielding tensors, and the total NMR spin-spin coupling constants. Three scaling factors, depending on the carbon atom hybridizations, were found for the (1)H-C-C-(1)H vicinal coupling constants: f((sp3)-(sp3)) = 0.910, f((sp3)-(sp2)) = 0.929, and f((sp2)-(sp2))= 0.977. A remarkable correlation between the theoretical (J(pre)) and experimental (1)H-(1)H NMR (J(exp)) coupling constants for spicigerolide (1), a cytotoxic natural product, and some of its synthetic stereoisomers (2-4) demonstrated the predictive value of this approach for the stereochemical assignment of highly flexible compounds containing multiple chiral centers. The stereochemistry of two natural 6-heptenyl-5,6-dihydro-2H-pyran-2-ones (14 and 15) containing diverse functional groups in the heptenyl side chain was also analyzed by application of this combined theoretical and experimental approach, confirming its reliability. Additionally, a geometrical analysis for the conformations of 1-8 revealed that weak hydrogen bonds substantially guide the conformational behavior of the tetraacyloxy-6-heptenyl-2H-pyran-2-ones.
authors.affiliation: Departamento de Química y Programa de Posgrado en Farmacología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, A.P. 14-470, México, D. F. 07000 Mexico.
authors.forename: Fabian
authors.initials: F
authors.lastname: López-Vallejo
authors.forename: Mabel
authors.initials: M
authors.lastname: Fragoso-Serrano
authors.forename: Gloria Alejandra
authors.initials: GA
authors.lastname: Suárez-Ortiz
authors.forename: Adriana C
authors.initials: AC
authors.lastname: Hernández-Rojas
authors.forename: Carlos M
authors.initials: CM
authors.lastname: Cerda-García-Rojas
authors.forename: Rogelio
authors.initials: R
authors.lastname: Pereda-Miranda
mesh_terms: D005456:Fluorescent Dyes / Q000737:chemistry*; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D011753:Pyrones / Q000737:chemistry*; D011789:Quantum Theory; D013237:Stereoisomerism
chemical_list: C569087:6-heptenyl-5,6-dihydro-2H-pyran-2-one; D005456:Fluorescent Dyes; D011753:Pyrones