•The crotofolanes, crotodichogamoin A and B isolated from Croton dichogamus.•The halimanes, crothalimene A and B, isolated from Croton dichogamus.•Crotofolane, casbane, furanohalimane and patchoulene diterpenoids isolated.Four previously undescribed diterpenoids including two crotofolanes, crotodichogamoin A and B, and two halimanes, crothalimene A and B, a new sesquiterpenoid, and fifteen previously reported compounds, including the crotofolane, crotohaumanoxide, the casbane, depressin, a further seven furanohalimane diterpenoids, three patchoulane and two further cadinane sesquiterpenoids and aleuritolic acid were isolated from the root of Croton dichogamus. Crotodichogamoin B is an important biosynthetic intermediate of the crotofolane class and this is the first report of patchoulene sesquiterpenoids from the genus. Compounds were tested at one concentration, 1 × 10−5 M, in the NCI59 cell one-dose screen but did not show significant activity snd were also evaluated for their cytotoxicity against Caco-2 cell lines using the neutral red assay. 10-epi-Maninsigin D reduced Caco-2 cell viability at 10, 30 and 100 μM, with values of decreased viability of 28%, 48% and 43% respectively. None of the other tested compounds showed significant activity.Download high-res image (280KB)Download full-size image

The bulbs of Eucomis bicolor (Hyacinthoideae) yielded fourteen novel natural compounds, including (17S)-3-oxo-24,25,26,27,28-pentanorlanost-8-en-23,17α-olide, whose structure was determined using the logic for structure determination program, and nine novel lanosterol glycosides. Compounds were screened against the NCI-59 cancer cell panel but showed limited activity.

Nine triterpenoid derivatives were isolated from the heartwood of Xylocarpus rumphii and were identified as xylorumphiins E (1), C (2), L (3), and M–R (4–9). Compounds 4–9 have a hemiacetal group in the triterpenoid side chain, making them impossible to purify. Purification was achieved after acetylation and subsequent separation of the epimeric mixtures of acetates; however differentiaition of the R and S epimers was not possible using standard NMR techniques. In one case, the relative configuration of a remotely located stereocenter with respect to the stereocenters in the main skeleton was unambiguously determined using residual dipolar couplings. Dipolar couplings were collected from the sample oriented in compressed poly(methyl methacrylate) gels swollen in CDCl3. In another case, the relative configuration was determined using 1D selective quantitative NOE experiments. Xylorumphiin K (10), xyloccensin E, taraxer-14-en-3β-ol, (22S)-hydroxytirucalla-7,24-diene-3,23-dione, and 25-hydroxy-(20S,24S)-epoxydammaran-3-one were isolated from the bark of the same plant. Compounds 3–10 are new compounds. Compounds 1–6 and xyloccensin E were tested at one concentration, 1 × 10–5 M, in the NCI59 cell one-dose screen but did not show significant activity.

•Ovatifolionone acetate showed a good degree of COX-2 selectivity.•Five compounds were isolated from Ledebouria socialis and L. ovatifolia.•Compounds isolated showed COX-1 and COX-2 activity.•Circular dichroism was used to establish absolute configurations.The bulbs of Ledebouria socialis (Hyacinthaceae) yielded the benzocyclobutene homoisoflavonoid, (R)-2′,5-dihydroxy-3′,4′,7-trimethoxyspiro{2H-1-benzopyran-3-(4H)-9-bicyclo[4.2.0]octa[1,3,5]triene}-4-one, socialinone (1). Ledebouria ovatifolia yielded (2ε,3R)-2,5-dihydroxy-7-methoxyspiro[2H-1-benzopyran-3(4H), 5′(6′H)-cyclobuta[f][1,3]benzodioxol]-4-one (2) and the homoisoflavanone, (E)-3-(3′,4′-dihydroxybenzylidene)-5,7-dihydroxychroman-4-one, ovatifolionone (5), the dihydrochalcone, 4,4′-dihydroxy-2′,6′-dimethoxydihydrochalcone (3), and xanthone, 1,6-dihydroxy-2,3,5-trimethoxy-8-methyl-9H-xanthen-9-one (4) along with 21 known compounds. Structures were determined using spectroscopic techniques. The anti-inflammatory activities of the homoisoflavonoids and xanthones isolated were evaluated against cyclooxygenase-1 and -2 isoenzymes. (R)-3-(3′,4′-Dihydroxybenzyl)-7-hydroxy-5-methoxychroman-4-one (7), (E)-3-(3′,4′-dihydroxybenzylidene)-7-hydroxy-5-methoxychroman-4-one (10), 1,3,6-trihydroxy-2-methoxy-8-methylxanthen-9-one (6) and ovatifolionone acetate (5Ac) exhibited significant activity against cyclooxygenase-2 at <10 μM.Homoisoflavonoids, including (E)-3-(3′,4′-dihydroxybenzylidene)-5-acetoxy-7-hydroxychroman-4-one (ovatifolionone acetate) and (E)-3-(3′,4′-dihydroxybenzylidene)-7-hydroxy-5-methoxychroman-4-one, showed selective COX-2 inhibition.

Two new ent-kauren-19-oic acid derivatives, ent-14S*-hydroxykaur-16-en-19-oic acid and ent-14S*,17-dihydroxykaur-15-en-19-oic acid together with eleven known compounds ent-kaur-16-en-19-oic acid, ent-kaur-16-en-19-al, ent-12β-hydroxykaur-16-en-19-oic acid, ent-12β-acetoxykaur-16-en-19-oic acid, 8R,13R-epoxylabd-14-ene, eudesm-4(15)-ene-1β,6α-diol, (−)-7-epivaleran-4-one, germacra-4(15), 5E,10(14)-trien-9β-ol, acetyl aleuritolic acid, β-amyrin, and stigmasterol were isolated from the stem bark of Croton pseudopulchellus (Euphorbiaceae). Structures were determined using spectroscopic techniques. Ent-14S*-hydroxykaur-16-en-19-oic acid, ent-kaur-16-en-19-oic acid, ent-12β-hydroxykaur-16-en-19-oic acid, ent-12β-acetoxykaur-16-en-19-oic acid and 8R,13R-epoxylabd-14-ene were tested for their effects on Semliki Forest virus replication and for cytotoxicity against human liver tumour cells (Huh-7 strain) but were found to be inactive. Ent-kaur-16-en-19-oic acid, the major constituent, showed weak activity against the Plasmodium falciparum (CQS) D10 strain.Graphical abstractHighlights► Two novel ent-diterpenoids have been isolated along with a range of known ent-diterpenoids, sesquiterpenoids and triterpenoids. ► Following ethnomedicinal usage, compounds were tested for anti-viral activity against the Semliki virus but were found to be inactive. ► The major constituent showed moderate antiplasmodial activity against the chloroquine resistant strain of the malarial parasite Plasmodium falciparum.

Ten new cembranolides, (−)-(1R*,4R*,10R*)-4-methoxycembra-2E,7E,11Z-trien-20,10-olide (1), (−)-(1S*,4R*,10R*)-1-hydroxy-4-methoxycembra-2E,7E,11Z-trien-20,10-olide (2), (−)-(1S*,4S*,10R*)-1,4-dihydroxycembra-2E,7E,11Z-trien-20,10-olide (3), (−)-(1S*,4S*,10R*)-1,4-dihydroxycembra-2E,7E,11Z-trien-20,10-olide (4), (+)-(10R*)-cembra-1E,3E,7E,11Z,16-pentaen-20,10-olide (5), (+)-(10R*)-cembra-1Z,3Z,7E,11Z,15-pentaen-20,10-olide (6), (+)-(5R*,10R*)-5-methoxycembra-1E,3E,7E,11Z,15-pentaen-20,10-olide (7), (+)-(1S*,4S*,7R*,10R*)-1,4,7-trihydroxycembra-2E,8(19),11Z-trien-20,10-olide (8), (−)-(1S*,4S*,7S*,10R*)-1,4,7-trihydroxycembra-2E,8(19),11Z-trien-20,10-olide (9), and (+)-(1S*,4R*,8S*,10R*)-1,4,8-trihydroxycembra-2E,6E,11Z-trien-20,10-olide (10), together with six known compounds, lupeol, 4(15)-eudesmene-1β,6α-diol, α-glutinol, 24-ethylcholesta-4,22-dien-3-one, (+)-(1R*,10R*)-cembra-2E,4E,7E,11Z-tetraen-20,10-olide, and (+)-(1R*,4S*,10R*)-4-hydroxycembra-2E,7E,11Z-trien-20,10-olide (4a), have been isolated from the leaves of Croton gratissimus. The acetyl derivatives of 8 and 4a were evaluated against a chloroquine-sensitive strain of Plasmodium falciparum (D10).

The stem bark of Croton gratissimus (Euphorbiaceae) yielded four cembranolides, including the first reported example of a 2,12-cyclocembranolide, (+)-[1R*,2S*,7S*,8S*,12R*]-7,8-epoxy-2,12-cyclocembra-3E,10Z-dien-20,10-olide, whose structure was confirmed by means of single crystal X-ray analysis. This compound showed moderate activity against the PEO1 and PEO1TaxR ovarian cancer cell lines.The stem bark of Croton gratissimus (Euphorbiaceae) yielded four cembranolides, including the first reported example of a 2,12-cyclocembranolide, (+)-[1R*,2S*,7S*,8S*,12R*]-7,8-epoxy-2,12-cyclocembra-3E,10Z-dien-20,10-olide, whose structure was confirmed by means of single crystal X-ray analysis. This compound showed moderate activity against the PEO1 and PEO1TaxR ovarian cancer cell lines.

The limonoid derivative, methyl uguenenoate, the azole, uguenenazole, and the amide, uguenenonamide, together with the known furoquinoline alkaloids flindersiamine and maculosidine, and syringaldehyde have been isolated from the root of the East African Rutaceae Vepris uguenensis. While methyl uguenenoate and the furoquinoline alkaloids displayed mild antimalarial activity, the azole and amide were completely inactive.The limonoid, methyl uguenesonate, 1, the azole, uguenenazole, 2, and the amide, uguenenonamide, together with the known furoquinoline alkaloids flindersiamine and maculosidine, and syringaldehyde have been isolated from the root of the East African Rutaceae Vepris uguenensis.

Five 3-hydroxy-type homoisoflavonoids, 3,5-dihydroxy-7,8-dimethoxy-3-(3′,4′-dimethoxybenzyl)-4-chromanone, 3,5-dihydroxy-7-methoxy-3-(3′,4′-dimethoxybenzyl)-4-chromanone, 3,5-dihydroxy-7,8-dimethoxy-3-(3′-hydroxy-4′-methoxybenzyl)-4-chromanone, 3,5,6-trihydroxy-7-methoxy-3-(3′-hydroxy-4′-methoxybenzyl)-4-chromanone and 3,5,7-trihydroxy-3-(3′-hydroxy-4′methoxybenzyl)-4-chromanone in addition to the nortriterpenoid, 15-deoxoeucosterol, have been isolated from the dichloromethane extract of the bulbs of Pseudoprospero firmifolium, the sole representative of the tribe Pseudoprospereae of the subfamily Hyacinthoideae of the Hyacinthaceae.Five homoisoflavanones: 3,5-dihydroxy-7,8-dimethoxy-3-(3′,4′-dimethoxybenzyl)-4-chromanone, 3,5-dihydroxy-7-methoxy-3-(3′,4′-dimethoxybenzyl)-4-chromanone, 3,5-dihydroxy-7,8-dimethoxy-3-(3′-hydroxy-4′-methoxybenzyl)-4-chromanone, 3,5,6-trihydroxy-7-methoxy-3-(3′-hydroxy-4′-methoxybenzyl)-4-chromanone and 3,5,7-trihydroxy-3-(3′-hydroxy-4′methoxybenzyl)-4-chromanone and the nortriterpenoid, 15-deoxoeucosterol, have been isolated from the bulbs of Pseudoprospero firmifolium, the sole representative of the tribe Pseudoprospereae (Hyacinthaceae: Hyacinthoideae).

Two bufadienolides, 3β,16β-dihydroxy-5β-bufa-20,22-dienolide and 16β-hydroxy-5β-bufa-20,22-dienolide-3β-O-β-d-galactoside, have been isolated from bulbs of the poisonous South African geophyte Drimia depressa (Hyacinthaceae).Two bufadienolides, 3β,16β-dihydroxy-5β-bufa-20,22-dienolide and 16β-hydroxy-5β-bufa-20,22-dienolide-3β-O-β-d-galactoside, have been isolated from bulbs of the poisonous South African geophyte Drimia depressa (Hyacinthaceae).

The bufadienolides, rubellin and riparianin were isolated from the bulbs of Drimia macrocentra and Urginea riparia (Hyacinthaceae) respectively. Rubellin and riparianin contain a carbohydrate moiety doubly linked to the bufadienolide aglycone at the C-2 and C-3 positions. Riparianin showed moderate activity when tested against MCF7 (breast), TK10 (renal) and UACC62 (melanoma) cell lines.Rubellin and riparianin have been isolated from the bulbs of Drimia macrocentra and Urginea riparia (Hyacinthaceae) respectively. Rubellin and riparianin contain a carbohydrate moiety doubly linked to the bufadienolide aglycone at the C-2 and C-3 positions. Riparianin showed moderate activity when tested against MCF7 (breast), TK10 (renal) and UACC62 (melanoma) cancer cell lines.

The stem bark of Phyllanthus polyanthus (Phyllanthaceae) has yielded phyllanthol, phyllanthone, (20S)-3β-acetoxy-24-methylenedammaran-20-ol, δ-amyrin acetate and lupenone and the leaves yielded (20S)-3α-acetoxy-24-methylenedammaran-20-ol. NMR data for phyllanthol provided in the literature have been revised.The stem bark of Phyllanthus polyanthus (Phyllanthaceae) has yielded phyllanthol, phyllanthone, (20S)-3β-acetoxy-24-methylenedammaran-20-ol, 1, δ-amyrin acetate and lupenone and the leaves yielded (20S)-3α-acetoxy-24-methylenedammaran-20-ol. NMR data for phyllanthol provided in the literature have been revised.