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

被引:30
作者
Alejandra Suarez-Ortiz, G. [1 ]
Cerda-Garcia-Rojas, Carlos M. [2 ,3 ]
Hernandez-Rojas, Adriana [1 ]
Pereda-Miranda, Rogelio [1 ]
机构
[1] Univ Nacl Autonoma Mexico, Fac Quim, Dept Farm, Mexico City 04510, DF, Mexico
[2] Inst Politecn Nacl, Ctr Invest & Estudios Avanzados, Dept Quim, Mexico City 07000, DF, Mexico
[3] Inst Politecn Nacl, Ctr Invest & Estudios Avanzados, Programa Posgrad Farmacol, Mexico City 07000, DF, Mexico
来源
JOURNAL OF NATURAL PRODUCTS | 2013年 / 76卷 / 01期
关键词
MOLECULAR-FORCE FIELD; ALPHA-PYRONES; ELUCIDATION; GEOMETRIES; STEREOCHEMISTRY; SPICIGEROLIDE; PERFORMANCE; PIRONETIN; ASSAY;
D O I
10.1021/np300740h
中图分类号
Q94 [植物学];
学科分类号
071001 ;
摘要
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-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.
引用
收藏
页码:72 / 78
页数:7
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