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Complementarity of DFT Calculations, NMR Anisotropy, and ECD for the Configurational Analysis of Brevipolides K–O from Hyptis brevipes

Suárez-Ortiz, G. Alejandra, Cerda-García-Rojas, Carlos M., Fragoso-Serrano, Mabel, Pereda-Miranda, Rogelio
Journal of natural products 2017 v.80 no.1 pp. 181-189
Hyptis, anticarcinogenic activity, cytotoxicity, high performance liquid chromatography, inhibitory concentration 50, neoplasms, nuclear magnetic resonance spectroscopy, spectral analysis, tetrahydrofuran
Brevipolides K–O (1–5), five new cytotoxic 6-(6′-cinnamoyloxy-2′,5′-epoxy-1′-hydroxyheptyl)-5,6-dihydro-2H-pyran-2-ones (IC₅₀ values against six cancer cell lines, 1.7–10 μM), were purified by recycling HPLC from Hyptis brevipes. The structures, containing a distinctive tetrahydrofuran ring, were established by comprehensive quantum mechanical calculations and experimental spectroscopic analysis of their NMR and ECD data. Detailed analysis of the experimental NMR ¹H–¹H vicinal coupling constants in comparison with the corresponding DFT-calculated values at the B3LYP/DGDZVP level confirmed the absolute configuration of 3 and revealed its conformational preferences, which were further strengthened by NOESY correlations. NMR anisotropy experiments by the application of Mosher’s ester methodology and chemical correlations were also used to conclude that this novel brevipolide series (1–5) share the same absolute configuration corresponding to C-6(R), C-1′(S), C-2′(R), C-5′(S), and C-6′(S).