Furanocoumarins from Dorstenia foetida Ramona Heinke a , Katrin Franke a , Andrea Porzel a , Ludger A. Wessjohann a , Nasser A. Awadh Ali b , Jürgen Schmidt a,⇑ a Leibniz Institute of Plant Biochemistry, Department of Bioorganic Chemistry, Weinberg 3, D-06120 Halle/Saale, Germany b Pharmacognosy Department, Faculty of Pharmacy, Sana’a University, P.O. Box 13150, Sana’a, Yemen article info Article history: Received 1 February 2011 Received in revised form 9 March 2011 Available online 12 April 2011 Keywords: Dorstenia foetida Moraceae Phytochemistry Furanocoumarins 7-Hydroxy-5-methoxy-6-carboxymethyl-3- [3-(b-D-glucopyranosyloxy)-2-hydroxy-3- methyl-butyl]-coumarin abstract The linear furanocoumarins 5-(2,3-epoxy-3-methyl-butoxy)-chalepensin, 5-methoxy-3-(3-methyl- 2,3-dihydroxybutyl)-psoralen-diacetate (7), 5-methoxy-3-[3-(b-D-glucopyranosyloxy)-2-acetyloxy-3- methyl-butyl]-psoralen and 5-(3-methyl-2,3-dihydroxybutyloxy)-3-[3-(b-D-glucopyranosyloxy)-2- hydroxy-3-methyl-butyl]-psoralen, and the coumarin derivative 7-hydroxy-5-methoxy-6-carboxy- methyl-3-[3-(b-D-glucopyranosyloxy)-2-hydroxy-3-methyl-butyl]-coumarin were isolated from the leaves of Dorstenia foetida (Moraceae) along with the known compounds psoralen, bergapten, isopimpi- nellin, phellopterin, 5-methoxychalepensin and turbinatocoumarin. Further furanocoumarins were char- acterized by ESI-MS/MS investigations. The nonpolar extracts of D. foetida exhibit antifungal, antibacterial and cytotoxic activity, however, no anthelminthic activity. Ó 2011 Elsevier Ltd. All rights reserved. 1. Introduction Dorstenia is a herbaceous genus of the family Moraceae, found throughout the tropics, which is particularly rich in furanocouma- rins, an important class of plant phototoxins. Four species of this genus occur in Yemen and Socotra Island (Wood, 1997; Miller and Morris, 2004). Dorstenia foetida (Forssk.) Schweinf. is a gla- brous herb with a thick branched fleshy tuberous stem with numerous leaf scars. The succulent subshrub, which is distributed in Yemen, Saudi Arabia, Oman, Somalia, Ethiopia and Tanzania, is growing in deciduous and succulent bushland, on open places and rocks outcrops up to an altitude of 2100 m (Eggli, 2002). The juice of the aerial parts is used in local traditional medicine in Ye- men for treating skin diseases and in particular leishmaniasis (Awadh Ali et al., 2005). In northwest Ethiopia the root is orally used against leprosy, liver diseases and intestinal worms by the so- cio-cultural group of Amhara peoples (Giday et al., 2007). In Oman the cooked tuberous roots are used as food (Marwah et al., 2007). Up to now, only psoralen (1) and bergapten (2) and the presence of other furanocoumarins, which are not isolated and identified, have been reported for D. foetida (Swain and Downum, 1990). Furanocoumarins possess a variety of biological activities including antimicrobial, antifungal (Smith et al., 2004), antioxida- tive and antiinflammatory (Ban et al., 2003), estrogenic or anties- trogenic properties (Piao et al., 2006) as well as inhibitory effects on cytochrome P-450 enzymes (Guo and Yamazoe, 2004), on acetylcholine esterase (Kang et al., 2001), and on prostaglandin E 2 production (Ban et al., 2003). Our detailed phytochemical investigation of leaves of D. foetida collected in Yemen resulted in the characterization of four new fur- anocoumarins and one carboxymethyl coumarin derivative along with six known ones (Fig. 1). 2. Results and discussion The dried leaves of D. foetida were extracted with 80% EtOH. This extract was reduced to the aq. phase and partitioned successively with n-heptane, EtOAc and n-BuOH. Comprehensive chromatogra- phy of these extracts provided the four new linear furanocoumarins 5-(2,3-epoxy-3-methyl-butoxy)-chalepensin (6), 5-methoxy-3-(3- methyl-2,3-dihydroxybutyl)-psoralen-diacetate (7), 5-methoxy-3- [3-(b-D-glucopyranosyloxy)-2-acetyloxy-3-methyl-butyl]-psoralen (9) and 5-(3-methyl-2,3-dihydroxybutyloxy)-3-[3-(b-D-glucopyr- anosyloxy)-2-hydroxy-3-methyl-butyl]-psoralen (10), and the new coumarin derivative 11, which all are isolated for the first time as a natural product. Their planar structures were elucidated on basis of spectral data, the stereochemistry at chiral centres was not deter- mined. Further three novel furanocoumarins were characterized by mass spectral investigations (12–14). The compounds isopimpinel- lin (3), phellopterin (4), 5-methoxychalepensin (5) and turbinato- coumarin (8) are reported for the first time in D. foetida. Additionally the known furanocoumarins psoralen (1) and bergap- ten (2) were isolated. The structures of these compounds were 0031-9422/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.phytochem.2011.03.008 ⇑ Corresponding author. E-mail address: jschmidt@ipb-halle.de (J. Schmidt). Phytochemistry 72 (2011) 929–934 Contents lists available at ScienceDirect Phytochemistry journal homepage: www.elsevier.com/locate/phytochem