title: Complementarity of DFT Calculations, NMR Anisotropy, and ECD for the Configurational Analysis of Brevipolides K-O from Hyptis brevipes.
abstract: Brevipolides K-O (1-5), five new cytotoxic 6-(6'-cinnamoyloxy-2',5'-epoxy-1'-hydroxyheptyl)-5,6-dihydro-2H-pyran-2-ones (IC50values 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 NMR1H-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).
authors.affiliation: Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, Circuito Exterior Ciudad Universitaria , Mexico City 04510, Mexico.
authors.forename: G Alejandra
authors.initials: GA
authors.lastname: Suárez-Ortiz
authors.affiliation: Departamento de Química, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional , A. P. 14-740, Mexico City 07000, Mexico.
authors.forename: Carlos M
authors.initials: CM
authors.lastname: Cerda-García-Rojas
authors.affiliation: Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, Circuito Exterior Ciudad Universitaria , Mexico City 04510, Mexico.
authors.forename: Mabel
authors.initials: M
authors.lastname: Fragoso-Serrano
authors.affiliation: Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, Circuito Exterior Ciudad Universitaria , Mexico City 04510, Mexico.
authors.forename: Rogelio
authors.identifier: 0000-0002-0542-0085
authors.initials: R
authors.lastname: Pereda-Miranda
mesh_terms: D016880:Anisotropy; D002460:Cell Line; D006801:Humans; D031331:Hyptis / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D011753:Pyrones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D011789:Quantum Theory; D013237:Stereoisomerism
chemical_list: D011753:Pyrones