Absolute Configuration and Conformational Analysis of Brevipolides, Bioactive 5,6-Dihydro-alpha-pyrones from Hyptis brevipes

作者：Alejandra Suarez Ortiz G; Cerda Garcia Rojas Carlos M; Hernandez Rojas Adriana; Pereda Miranda Rogelio^*

来源：Journal of Natural Products, 2013, 76(1): 72-78.

DOI：10.1021/np300740h

The (6%26apos;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%26apos;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-alpha-pyrones was carried out on compound 9 by application of a protocol based on comparison between experimental and DFT-calculated vicinal H-1-H-1 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 (ED50 0.3-8.0 mu g/mL) against a variety of tumor cell lines.

• 出版日期2013-1