Planta Med 2008; 74 - PK7
DOI: 10.1055/s-0028-1084976

Conformational analysis of Hyptolide by DFT molecular modeling calculations and theoretical versus experimental NMR coupling constants analysis

JA Mendoza-Espinoza 1, F López-Vallejo 1, CM Cerda-García-Rojas 1, R Pereda-Miranda 2
  • 1Departamento de Química y Sección Externa de Farmacología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, A. P. 14–470, México, D. F. 07000 Mexico
  • 2Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, Circuito Exterior Ciudad Universitaria, México, D. F. 04510, Mexico

Hyptolide belongs to a relevant group of cytotoxic compounds which occur in several members of the Lamiaceae family [1]. The conformational analysis of this highly flexible polyacylated-6-heptenyl-5,6-dihydro-2H-pyran-2-one was ascertained by a molecular modeling protocol which includes extensive systematic conformational searching [2], geometry optimization by DFT B3LYP/DGDZVP calculations, and comparison between the theoretical (DFT-GIAO) and experimental 1H-1H NMR couplings [3]. For the 28 more stable conformations, the root mean square difference between the observed and calculated couplings was smaller than 1Hz assuring the accuracy of the models.

29.91%

21.16%

15.07%

6.96%

Acknowledgements: Financial support from Conacyt is acknowledged (grant 45759-Q). Geometry optimizations and coupling constant calculations were performed in the Kan-Balam cluster at DGSCA, UNAM.

References: 1. Achmad, S. A. et al. (1987) Acta Chem. Scand. 41B: 599–609.

2. Pereda-Miranda, R. et al. (2001) Tetrahedron 57: 47–53.

3. Wolinski, K. et al. (1990)J. Am. Chem. Soc. 112: 8251–8260.