ABSTRACT
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).
Subject(s)
Hyptis/chemistry , Pyrones/isolation & purification , Anisotropy , Cell Line , Humans , Inhibitory Concentration 50 , Magnetic Resonance Spectroscopy , Molecular Structure , Pyrones/chemistry , Pyrones/pharmacology , Quantum Theory , StereoisomerismABSTRACT
The (6'S)-configuration of brevipolides A-J (1-10), isolated from Hyptis brevipes, was established by X-ray diffraction analysis of 9 in conjunction with Mosher's ester analysis of the tetrahydro derivative 11 obtained from both geometric isomers 8 and 9 as well as by chemical correlations. The structure of the new brevipolide J (10) was characterized through NMR and MS data as having the same 6-heptyl-5,6-dihydro-2H-pyran-2-one framework possessing the cyclopropane moiety of all brevipolides but substituted by an isoferuloyl group instead of the p-methoxycinnamoyl moiety found in 8 and 9. Conformational analysis of these cytotoxic 6-heptyl-5,6-dihydro-α-pyrones was carried out on compound 9 by application of a protocol based on comparison between experimental and DFT-calculated vicinal (1)H-(1)H NMR coupling constants. Molecular modeling was used to correlate minimum energy conformers and observed electronic circular dichroism transitions for the isomeric series of brevipolides. Compounds 7-10 exhibited moderate activity (ED(50) 0.3-8.0 µg/mL) against a variety of tumor cell lines.
Subject(s)
Hyptis/chemistry , Pyrones/chemistry , Pyrones/isolation & purification , Circular Dichroism , Crystallography, X-Ray , Drug Screening Assays, Antitumor , Mexico , Molecular Conformation , Molecular Structure , Pyrones/pharmacology , StereoisomerismABSTRACT
The title compound, C(18)H(27)NO(2), crystallizes as the enamine form with Z geometry. The ß-enamino-ester fragment forms a dihedral angle of 87.5â (1)° with the isopropyl-phenyl frame. The structure exhibits an intra-molecular N-Hâ¯O hydrogen bond. In addition, in the crystal, mol-ecules are linked by a centrosymmetric inter-molecular N-Hâ¯O hydrogen bond.
ABSTRACT
The title compound, C(15)H(21)NO(2), was obtained by the reaction of acetoacetate with 2,4,6-trimethyl-aniline using Mexican bentonitic clay as a catalyst. It crystallizes in the enamine form. The ß-enamino ester residue is almost perpendicular to the aromatic ring [dihedral angle = 88.10â (6)°]. The mol-ecular conformation is stabilized by a strong intra-molecular N-Hâ¯O hydrogen bond. In addition, the N-H group forms a weak inter-molecular N-Hâ¯O hydrogen bond linking the mol-ecules into centrosymmetric dimers.
