Moses K. Langat

Cembranolides from the stem bark of the southern African medicinal plant, Croton gratissimus (Euphorbiaceae)

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.

Cembranolides from the Leaves of Croton gratissimus.

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).

New ent-clerodane and abietane diterpenoids from the roots of Kenyan Croton megalocarpoides Friis & M.G. Gilbert

The roots of the endangered medicinal plant Croton megalocarpoides collected in Kenya were investigated and twenty-two compounds isolated. Among them were twelve new ent-clerodane (1-12) and a new abietane (13) diterpenoids, alongside the known crotocorylifuran (4 a), two known abietane and four known ent-trachylobane diterpenoids, and the triterpenoids, lupeol and acetyl aleurotolic acid. The structures of the compounds were determined using NMR, HRMS and ECD. The isolated compounds were evaluated against a series of microorganisms (fungal and bacteria) and also against Plasmodium falciparum, however no activity was observed.

Application of Residual Dipolar Couplings and Selective Quantitative NOE to Establish the Structures of Tetranortriterpenoids from Xylocarpus rumphii

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.

Reducing copper use in the environment: The use of larixol and larixyl acetate to treat downy mildew caused by Plasmopara viticola in viticulture

BACKGROUND Plant extracts might provide sustainable alternatives to copper fungicides, which are still widely used despite their unfavourable ecotoxicological profile. Larch bark extract and its constituents, larixyl acetate and larixol, have been shown to be effective against grapevine downy mildew (Plasmopara viticola) under semi-controlled conditions. The aim of this study was to reduce the gap between innovation and the registration of a marketable product, namely to develop scalable extraction processes and to evaluate and optimise the performance of larch extracts under different conditions. RESULTS Toxicologically and technically acceptable solvents like ethanol were used to extract the active compounds larixyl acetate and larixol from bark in sufficient amounts and their combined concentration could be increased by up to 39% by purification steps. The combined concentration of larixyl acetate and larixol from larch turpentine could be increased by up to 66%. The Minimal Inhibitory Concentration (MIC100 ) against P. viticola in vitro (6-23 µg mL-1 ) and the Effective Concentration (EC50 ) in planta under semi-controlled conditions (0.2-0.4 mg mL-1 ) were promising compared with other plant extracts. In vineyards, efficacies of larch extracts reached up to 68% in a stand-alone strategy and 84% in low-copper strategies. CONCLUSION Larch extracts represent valid candidates for copper reduction in organic vineyards, and their development into a sustainable plant protection product might be feasible.

Alienusolin, a new 4α-deoxyphorbol ester derivative, and crotonimide C, a new glutarimide alkaloid from the Kenyan Croton alienus.

Two novel compounds, alienusolin, a 4α-deoxyphorbol ester (1), crotonimide C, a glutarimide alkaloid derivative (2), and ten known compounds, julocrotine (3), crotepoxide (4), monodeacetyl crotepoxide (5), dideacetylcrotepoxide, (6), β-senepoxide (7), α-senepoxide (8), (+)-(2S,3R-diacetoxy-1-benzoyloxymethylenecyclohex-4,6-diene (9), benzyl benzoate (10), acetyl aleuritolic (11), and 24-ethylcholesta-4,22-dien-3-one (12) were isolated from the Kenyan Croton alienus. The structures of the compounds were determined using NMR, GCMS, and HRESIMS studies.

Laevifins A–G, clerodane diterpenoids from the Bark of Croton oblongus Burm.f.

A phytochemical investigation of the stem barks of the Malaysian Croton oblongus Burm.f. (Syn. Croton laevifolius Blume) (Euphorbiaceae) yielded seven previously undescribed ent-neo-clerodane diterpenoids, laevifins A - G and the known crovatin (3). Structures were established by a combination of spectroscopic methods including HRESIMS, NMR spectroscopy and X-ray crystallography. The absolute configuration of crovatin and laevifins A-G was established by comparison of experimental ECD and theoretical TDDFT ECD calculated spectra. This is the first report on the occurrence of the sesquiterpenoid cryptomeridiol in a Croton species. In vitro cytotoxicity assays on laevifins A, B and G showed moderate activities against the MCF-7 cancer cell line (IC50 102, 115 and 106 μM, respectively) while β-amyrin and acetyl aleuritolic acid showed good anti-inflammatory activity on the LPS-induced NF-κB translocation inhibition in RAW 264.7 cells assay with IC50 values of 23.5 and 35.4 μg/mL, respectively.

Ent-abietane diterpenoids from Suregada zanzibariensis Baill. (Euphorbiaceae), their cytotoxic and anticancer properties

Abstract The stem bark extract of Suregada zanzibariensis afforded a previously undescribed ent-abietane diterpenoid trivially named mangiolide (1) and a known jolkinolide B (2) via anticancer bioassay-guided fractionation. The CH2Cl2:MeOH extract of S. zanzibariensis was initially analysed for its anticancer properties against three cancer cell lines, renal (TK10), melanoma (UACC62), and breast (MCF7) and was found to be potent at low μg/mL ranges. Compound 1, 6α-acetoxy-14-keto-ent-abieta-7(8),13(15)-diene-16,12-olide (mangiolide) inhibited the growth of renal (TK10) with a GI50 of 0.02 μg/mL; a GI50 of 0.03 μg/mL for melanoma (UACC62) and a GI50 of 0.05 μg/mL for breast (MCF7) cancer cell lines. Compound 2, 8,13-diepoxy-13,15-ent-abietene-16,12-olide (jolkinolide B) inhibited the growth (GI50) of the cell lines at 3.31 μg/mL for renal (TK10), 0.94 μg/mL for melanoma (UACC62) and 2.99 μg/mL for the breast (MCF7). The structures were established on the basis of their spectroscopic analysis and the absolute stereostructures assigned using electronic circular dichroism (ECD).

Pumilol, a Diterpenoid with a Rare Strobane Skeleton from Pinus pumila (Pinaceae)

Pumilol (1), a strobane diterpenoid, reported herein for the first time, was isolated from the bark of Pinus pumila (Pall.) Regel (Siberian Dwarf Pine or Japanese Stone Pine), along with 17 known compounds including serratane triterpenoids, not previously reported from this species, and four ferulate derivatives. The absolute configuration of pumilol was established using HR‐ESI‐MS, NMR, the DP4+ probabilities and by comparison of the experimental and calculated electronic circular dichroism (ECD) spectra. Labda‐8(17),13‐dien‐15‐oic acid (4), bornyl (E)‐4‐hydroxycinnamate (14) and bornyl (E)‐ferulate (15) showed activity against S. aureus and/or E. faecalis with MIC90 values 12.5 – 50 μm.

Novel triterpenoid derivatives from Eucomis bicolor Bak. (Hyacinthaceae: Hyacinthoideae)

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.