A bioassay-guided fractionation of the EtOH extract of the Madagascan plant Terminalia calcicola H. Perrier (Combretaceae) led to the isolation of two new cytotoxic xanthones, termicalcicolanone A (1) and termicalcicolanone B (2). The structures of the new compounds were established on the basis of one and two dimensional NMR spectroscopic data. Both compounds showed modest antiproliferative activity toward the A2780 human ovarian cancer cell line.In our continuing search for bioactive molecules from the Madagascar rainforests as part of an International Cooperative Biodiversity Group (ICBG) program, 1 we obtained extracts of various parts of the tree Terminalia calcicola H. Perrier (Combretaceae) collected in Madagascar. The EtOH extract of the immature fruit proved to have moderate antiproliferative activity, with an IC 50 value of 14 µg/mL against the A2780 human ovarian cancer cell line. This extract was thus selected for bioassay-guided fractionation based on its cytotoxicity and also on the absence of any previous detailed phytochemical studies on this species.Previous phytochemical studies have revealed the genus of Terminalia to be a rich source of secondary metabolites, such as lignans, 2 flavonoids, 3 terpenoids, 4 and tannins. 5 Some of these metabolites have shown a wide range of biological activities, including anti-HIV-1, 2 antimalarial, 2 antifungal, 2,4 antibacterial, 4,6 and cytotoxic 5 activities. The anthelminthic and haemolytic properties of the terpene esters from T. macroptera have been studied. 4 The antioxidant effects of aqueous extract of T. chebula have also been investigated. 7Activity-guided fractionation of the dichloromethane extract (IC 50 , 10 µg/mL) by passage over a C18 open column, followed by purification of active fractions using C18 HPLC, led to the isolation of the two new compounds, 1 and 2. Table 1, including one carbonyl group, two aromatic rings with six oxygenated carbons, and two prenyl groups. The H-1″ resonance appeared at δ H 4.68, which was a more deshielded value than that usually found for this functionality, due to the effect of the C-9 carbonyl group. 9 Clearly, both the C-1 hydroxy and the C-8 3-methyl-but-2-enyl groups were peri to the carbonyl group. The ortho coupled aromatic H-5 and H-6 showed 3 J HMBC correlations (Figure 1) to C-7 and C-8a, and C-8 and C-10a, respectively, while H-1″ correlated to C-7, C-8, C-8a, C-2″, and C-3″, which provided further evidence for the position of the 3-methyl-but-2-enyl group at C-8. The HMBC correlations between the hydrogen-bonded proton (1-OH) and C-1, C-2, and C-9a, H-1′ and C-1, and H-2′ and C-2 were also observed, indicating that the 3′,3′-dimethylpyrano ring was fused at C-2 and C-3, which was confirmed by a ROESY correlation between the hydrogenbonded proton and H-1′. Based on the molecular formula of 1, the remaining two hydroxy groups must be located at C-4 and C-7, respectively. Thus, the structure of 1 was determined to be 5,8,12Termicalcicolanone B (2) was also obtained as a yellow powder. It was ...

Antimalarial bioassay-guided fractionation of an EtOH extract of the root wood of Cryptocarya rigidifolia (Lauraceae) led to the isolation of the five new 5,6-dihydro-α-pyrones cryptorigidifoliols A–E (1–5) and the six bicyclic tetrahydro-α-pyrone derivatives cryptorigidifoliols F–K (6–11). The structure elucidations of all compounds were made on the basis of the interpretation of spectroscopic data and chemical derivatization, and the relative and absolute configurations were determined by NOESY, electronic circular dichroism (ECD), and 1H NMR analysis of α-methoxyphenylacetyl (MPA) derivatives. The bicyclic tetrahydro-α-pyrone derivatives were identified as products of acid-catalyzed intramolecular Michael addition of the 5,6-dihydro-α-pyrones in the presence of silica gel. A structure–activity relationship study suggested that the presence of an α,β-unsaturated carbonyl moiety is not essential for potent antimalarial activity.

Bioassay-guided fractionation of the ethanol extract obtained from the fruits of Rheedia calcicola led to the isolation of two new guttiferone analogues, guttiferones K (1) and L (16-hydroxyguttiferone K) (2). The structures of 1 and 2 were established on the basis of extensive interpretation of one and two dimensional NMR spectroscopic data. Both compounds were tested for their antiproliferative activity against the A2780 human ovarian cancer cell line.As part of our continuing investigation of Madagascar plants for cytotoxic principles, 1 we found that an ethanol extract (MG 2796) of the fruits of Rheedia calcicola Jum. & H. Perrier (Clusiaceae) showed cytotoxicity in the A2780 assay with an IC 50 value of 15 µg/mL. This extract was selected for bioassay-guided fractionation based on its cytotoxicity against the A2780 human ovarian cancer cell line, and also on the absence of any previous chemical investigation of the species. Our bioassay-guided fractionation of Rheedia calcicola resulted in the isolation of two new cytotoxic guttiferone analogues, guttiferones K (1) and L (16-hydroxyguttiferone K) (2)The genus Rheedia has been found to be a rich sources of xanthones, 2-4 biflavonoids, 5-7 polyisoprenylated benzophenones (7-and 15-epiclusianone and xanthochymol), 7-9 and triterpenoids. 10 Their biological properties including brine shrimp lethality, 11 as well as antibacterial 10,11 and analgesic activity, 6 have been reported. 7-Epiclusianone and xanthochymol showed anti-HIV activity, 12 and xanthochymol also displayed antimicrobial activity 13 and cytotoxicity. 14 There is no information on traditional uses of the plant, and only lemurs eat its fruit. 15Extract MG 2796 was partitioned between hexane, CH 2 Cl 2 , and MeOH, and the CH 2 Cl 2 extract was found to be the most active with an IC 50 value of 10 µg/mL. The CH 2 Cl 2 extract was purified by filtration through a C18 cartridge followed by HPLC on a C18 column to yield compound 1 from the second fraction. Further HPLC separation of the first fraction using a C8 column yielded compound 2.*To whom correspondence should be addressed. Tel: (540) (Table 1) exhibited the presence of a 1,2,4-trisubstituted benzene ring. Four olefinic protons, one tertiary methyl and eight vinyl methyl groups, six methylenes, and one methine were also observed in the 1 H NMR and HSQC spectra of 1, indicating the presence of four 3-methylbut-2-enyl groups and a fifth C5 unit.The 13 C NMR spectrum of 1 ( (Figure 1) indicated the presence of two fragments, I (a 3,4-dihydroxybenzoyl group) and II (a 2,2-dimethylbicyclo[3.3.1]nonane ring system substituted with four 3-methylbut-2-enyl groups). The 1 H and 13 C NMR spectra of 1 were very similar to those of guttiferone A (3) 12b suggesting that 1 was a stereoisomer of guttiferone A. The correlations between CH 3 -22 and CH 2 -17/H-7α in the ROESY spectrum of 1 indicated that CH 3 -22 (δ H 0.81/δ C 16.4, in CD 3 OD/0.1%TFA) must be in the α-orientation like CH 2 -17. The 13 C NMR chemical shift of C-6 at δ C 42.0 in CD 3 OD/...