DFT 1H-1H coupling constants in the conformational analysis and stereoisomeric differentiation of 6-heptenyl-2H-pyran-2-ones: configurational reassignment of synargentolide A

• Published in: Magnetic resonance in chemistry Vol. 53; no. 3; pp. 203 - 212
• Main Authors: Juárez-González, Francisco, Suárez-Ortiz, Gloria Alejandra, Fragoso-Serrano, Mabel, Cerda-García-Rojas, Carlos M., Pereda-Miranda, Rogelio
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.03.2015; Wiley Subscription Services, Inc
• Subjects: 1H-1H coupling constants; configuration; conformational analysis; density functional calculations; Molecular Conformation; NMR spectroscopy; Proton Magnetic Resonance Spectroscopy; Pyrans - chemistry; Pyrones - chemistry; spectral simulation; Spectrometry, Mass, Electrospray Ionization; Stereoisomerism; synargentolide A; density functional calculations; 1H-1H coupling constants; configuration; conformational analysis; spectral simulation; NMR spectroscopy; synargentolide A
• ISSN: 0749-1581; 1097-458X
• DOI: 10.1002/mrc.4178

Density functional theory (DFT) 1H–1H 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 3JH,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. Copyright © 2014 John Wiley & Sons, Ltd. DFT 1H–1H NMR coupling constant calculations, including solvation parameters with the polarizable continuum model, together with the experimental values measured by spectral simulation, were used to predict the stereochemistry of flexible and highly polyoxygenated 6‐heptenyl‐5,6‐dihydro‐2H‐pyran‐2‐ones with multiple chiral centers allowing epimer differentiation. Using this DFT NMR integrated approach, the configurational reassignment of synargentolide A was accomplished.