Additional constituents from Heterotheca inuloides. Absolute configuration of some cadinanes

H. inuloides is one of the plants most used in the Mexican folk medicine and its applications are mainly related with the treatment of inflammatory processes [1]. Cadinane type sesquiterpenes are considered representative constituents of this species, however, the absolute configuration of some of them has not been defined. In the present investigation triterpenes, flavonoids, sterols and eight cadinanes (1 – 8) were isolated from the aerial parts of H. inuloides. Among these, 1 – 4 have not yet been described in the literature. The structures of these metabolites were elucidated on the basis of 1D and 2D NMR spectroscopic data analysis and confirmed by X-ray crystallographic analyses of the majority of them. The absolute configurations of compounds 2 – 5 were determined by comparing their experimental CD spectra with those calculated by the SCF-CI-DV MO method, and further checked via refinement of the Flack parameter using anomalous X-ray scattering from the oxygen atoms and chemical correlation methods. The 4R,10S configuration for compound 2 is the opposite to that of (+)-δ-cadinene isolated from Gossypium hirsutum. These findings are in agreement with previous investigations [2] and allowed to conclude that G. hirsutum and H. inuloides biosynthesize cadinanes of opposite enantiomeric series. All sesquiterpene compounds were evaluated for their anti-inflammatory potential applying the TPA-induced mouse ear edema model. The results revealed that some of these compounds display moderated activity.

References:

[1] Delgado G, Olivares M, Chávez M, Ramírez-Apan T, Linares E, Bye R, Espinosa-García F. Antiinflamatory Constituents from Heterotheca inuloides. J. Nat. Prod 2001; 64: 861 – 864.

[2] Stipanovic RD, Puckhaber LS, Reibenspies JH, Williams HJ. The absolute configuration of (-)-3-hydroxy-α-calacorene. Phytochemistry 2006; 67: 1304 – 1308.