Secondary metabolites of the genus Marrubium: Strategies of isolation and structure elucidation

Previous investigations on Marrubium velutinum and M. cylleneum revealed that these plants are a rich source of diterpenes, phenylethanoid glycosides and flavonoids [1,2,3], with interesting biological activities. Immunomodulating effects of a series of diterpenes [4] and the possible synergistic inhibitory activity against mushroom tyrosinase of the different compounds of the methanol extract [5] stimulated us to continue our research on this genus, with the phytochemical investigation of M. thessalum, another Greek endemic species. The plant proved to have a rich load of chemical constituents and its investigation is still in progress. For the isolation of the various compounds from the aerial parts diverse chromatographic methods of separation were employed, i.e. CC, TLC and RP-HPLC. Their structures were established mainly by means of 1D and 2D NMR (¹H-NMR, ¹³C-NMR/DEPT, ¹H-¹H COSY, NOESY, HSQC, HMBC). Isolation and structure elucidation problems of these classes of secondary metabolites are discussed. Isolation and structure elucidation of diterpenes proved to be a challenge due to the presence of epimeric mixtures. Pivotal role in the study of the phenylethanoid glycosides had the ¹³C-NMR spectra and HSQC-TOCSY technique, because they give valuable information concerning the sugars attached to the basic core of the molecule.

Acknowledgements: Argyropoulou C gratefully acknowledges financial support from the Alexander S. Onassis foundation. The authors wish to thank Dr. Th. Constantinidis for the identification of the plant.

References: 1. Karioti, A. et al. (2003) Phytochemistry 64:655–660.

2. Karioti, A. et al. (2005a) Z. Naturforsch. 60b:328–332.

3. Karioti, A. et al. (2005b) Phytochemistry 66:1060–1066.

4. Karioti, A. et al. (2007) Phytochemistry 68:1587–1594.

5. Karioti, A. et al. (2007) Bioorg. Med. Chem. 15:2708–2714.