Cornutins C–L, neo-clerodane-type diterpenoids from Cornutia grandifolia var. intermedia § Kristina Jenett-Siems a, *, Inga Ko¨hler a , Carola Kraft a , Karsten Siems b , Pablo N. Solis c , Mahabir P. Gupta c , Ulrich Bienzle d a Institut fu ¨r Pharmazie (Pharmazeutische Biologie), Freie Universita ¨t Berlin, Ko ¨nigin-Luise-Str. 2-4, D-14195 Berlin, Germany b Analyticon Discovery GmbH, D-14473 Potsdam, Germany c Centro de Investigationes Farmacognosticas de la Flora Panamen ˜a (CIFLORPAN), Facultad de Farmacia, Universidad de Panama ´, Panama d Institut fu ¨r Tropenmedizin, Medizinische Fakulta ¨t der Charite ´, Humboldt-Universita ¨t, D-14050 Berlin, Germany Received 25 February 2003; received in revised form 20 May 2003 Abstract Ten novel neo-clerodane diterpenoids, named cornutins C–L, have been isolated from the leaves of Cornutia grandifolia var. intermedia. Their structures have been elucidated by detailed spectroscopic analysis. In addition, the in vitro antiplasmodial activity of four isolated compounds (cornutin C–F) has been evaluated, revealing only a marginal activity. # 2003 Elsevier Ltd. All rights reserved. Keywords: Cornutia grandifolia var. intermedia; Verbenaceae; Cornutins; Neo-clerodane diterpenoids; Plasmodium falciparum 1. Introduction The neotropical genus Cornutia belonging to the family Verbenaceae comprises about 25 species. Cornu- tia grandifolia var. intermedia Moldenke is a shrub or small tree with large many-flowered inflorescences and blue or violet flowers. The species is native to Central American rainforests from Guatemala to Panama (Moldenke, 1973). It is used as a remedy against fever in Panama (Gupta et al., 1986). Earlier investigations of the leaves of C. grandifolia yielded the cornutins A and B, neo-clerodane-type diterpenoids with repellent activ- ity against leafcutter ants (Chen et al., 1992). During our ongoing investigations on antiplasmodial plant species from Central America, we isolated ten novel diterpenoids, named cornutins C–L (1–10), from the leaves of C. grandifolia var. intermedia. 2. Results and discussion Ground, dried leaves of C. grandifolia var. intermedia were extracted at room temperature with a mixture of petrolether–EtOAc (1:1). After evaporation of the sol- vent, the oily residue was fractionated by MPLC over RP-18 material with H 2 O–MeOH mixtures and MeOH to yield 16 fractions. Successive chromatographic pur- ification finally led to the isolation of ten novel diterpe- noids (1–10). Compound 1 displayed a molecular ion peak at m/z 366 in the EIMS, as well as characteristic fragments at m/z 348 [M–H 2 O] and m/z 97. Its molecular formula was determined as C 20 H 30 O 6 (HREIMS). The 1 H and 13 C NMR spectra revealed the presence of a -sub- stituted furan moiety (Tables 1 and 2). One of the furan protons ( 6.33, br s) showed HMBC correlations to a hydroxymethine carbon atom at  63.6. The fragment at m/z 97 in the EIMS could thus be explained by the loss of a furan-CHOH-moiety from the molecule. The cor- responding proton of the hydroxymethine residue ( 4.82, dd, J=9.5; 2.0 Hz) was coupled to a methylene group at  2.51 (1H, dd, J=9.5; 16.0 Hz) and  1.69 (1H, dd, J=16.0; 2.0 Hz). This methylene group showed long-range correlations to four further carbon atoms: 0031-9422/$ - see front matter # 2003 Elsevier Ltd. All rights reserved. doi:10.1016/S0031-9422(03)00352-2 Phytochemistry 64 (2003) 797–804 www.elsevier.com/locate/phytochem § Part 10 in the series ‘‘Herbal remedies traditionally used against malaria’’, for part 9 see Jenett-Siems et al. (2003). * Corresponding author. Tel.: +49-30-83853720; fax: +49-30- 83853729. E-mail address: kjsiems@zedat.fu-berlin.de (K. Jenett-Siems).