Bioactive sesquiterpene pyridine alkaloids from Maytenus aquifolium

Two new sesquiterpene evoninate alkaloids, were isolated together with the known compounds syringaresinol and 4'-O-methyl-(-)-epigallocatechin from the root bark of Maytenus aquifolium. The structures of the two alkaloids were elucidated by interpretation of their spectral data, and both exhibited very weak activity in a mechanism-based DNA-modifying yeast assay. (C) 1998 Elsevier B.V. Ltd. All rights reserved.

Further sesquiterpene pyridine alkaloids from Maytenus aquifolium

Two new sesquiterpene evoninate alkaloids, aquifoliunine E-III and aquifoliunine E-IV, were isolated from the root bark of Maytenus aquifolium. The structures of the new compounds were elucidated on the basis of spectroscopic methods, including ES-MS.

Antiprotozoal Sesquiterpene Pyridine Alkaloids from Maytenus ilicifolia

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Pteridine-, thymidine-, choline- and imidazole-derived alkaloids from the Australian ascidian, Leptoclinides durus

Four new acylated pteridine alkaloids, duramidines A-D, two new acylated thymidine alkaloids, leptoclinidines A and B, two new 1-acylglyceryl-3-(O- carboxyhydroxymethylcholine) alkaloids, durabetaines A and B, three new 1,3-dimethyl-5-methylsulfanylimidazole alkaloids, leptoclinidamines D-F, and the known alkaloids leptoclinidamines B and C and 6-bromo-1H-indolo-3-yl-oxoacetic acid methyl ester were isolated from the Australian ascidian Leptoclinides durus. The duramidines are the first pteridine alkaloids, possessing a three carbon side chain esterified at C-1′ with a 4-hydroxy-2′- methoxycinnamic acid, and are either hydroxylated or sulfated at C-2′. The leptoclinidines are the first 3′-indole-3-carboxylic acid ester derivatives of thymidine to be reported in the literature. The durabetaines are the first glyceryl-3-(O-carboxyhydroxymethylcholine) alkaloids to be reported from an animal source and are also the only known derivatives from this class to be acylated with aromatic carboxylic acids. MS and NMR data analysis established the structures of the new compounds. All compounds were shown to be inactive when tested for cytotoxic activity against prostate (LNCaP) and breast (MDA-MB-231) cancer cell lines and antimicrobial activity against Pseudomonas aeruginosa and Staphylococcus aureus.

Isolation, structure determination and cytotoxicity studies of tryptophan alkaloids from an Australian marine sponge Hyrtios sp

Mass-guided fractionation of the MeOH extract from a specimen of the Australian marine sponge Hyrtios sp. resulted in the isolation of two new tryptophan alkaloids, 6-oxofascaplysin (2), and secofascaplysic acid (3), in addition to the known metabolites fascaplysin (1) and reticulatate (4). The structures of all molecules were determined following NMR and MS data analysis. Structural ambiguities in 2 were addressed through comparison of experimental and DFT-generated theoretical NMR spectral values. Compounds 1–4 were evaluated for their cytotoxicity against a prostate cancer cell line (LNCaP) and were shown to display IC50 values ranging from 0.54 to 44.9 μM.

Ecionines A and B, two new cytotoxic pyridoacridine alkaloids from the Australian marine sponge, Ecionemia geodides

Chemical investigations of the Australian marine sponge Ecionemia geodides resulted in the isolation of two new pyridoacridine alkaloids, ecionines A (1) and B (2), along with the previously isolated marine natural products, biemnadin (3) and meridine (4). Compounds 1 and 2 both contain an imine moiety, which is rare for the pyridoacridine structure class. The chemical structures of 1 and 2 were determined by extensive 1D and 2D NMR and MS data analyses. All compounds were tested against a panel of human bladder cancer cell lines, the increasingly metastatic TSU-Pr1 series (TSU-Pr1, TSU-Pr1-B1 and TSU-Pr1- B2) and the superficial bladder cancer cell line 5637. Ecionine A (1) displayed cytotoxicity against all cell lines, with IC50 values ranging from 3 to 7 mM. This is the first report of chemistry from the sponge genus Ecionemia.

Cytotoxic C20 diterpenoid alkaloids from the Australian endemic rainforest plant Anopterus macleayanus

In order to identify new anticancer compounds from nature, a prefractionated library derived from Australian endemic plants was generated and screened against the prostate cancer cell line LNCaP using a metabolic assay. Fractions from the seeds, leaves, and wood of Anopterus macleayanus showed cytotoxic activity and were subsequently investigated using a combination of bioassay-guided fractionation and mass-directed isolation. This led to the identification of four new diterpenoid alkaloids, 6α-acetoxyanopterine (1), 4′-hydroxy-6α-acetoxyanopterine (2), 4′-hydroxyanopterine (3), and 11α-benzoylanopterine (4), along with four known compounds, anopterine (5), 7β-hydroxyanopterine (6), 7β,4′-dihydroxyanopterine (7), and 7β-hydroxy-11α-benzoylanopterine (8); all compounds were purified as their trifluoroacetate salt. The chemical structures of 1–8 were elucidated after analysis of 1D/2D NMR and MS data. Compounds 1–8 were evaluated for cytotoxic activity against a panel of human prostate cancer cells (LNCaP, C4-2B, and DuCaP) and nonmalignant cell lines (BPH-1 and WPMY-1), using a live-cell imaging system and a metabolic assay. All compounds showed potent cytotoxicity with IC50 values of <400 nM; compound 1 was the most active natural product from this series, with an IC50 value of 3.1 nM toward the LNCaP cell line. The live-cell imaging assay on 1–8 showed a concentration- and time-dependent effect on the cell morphology and proliferation of LNCaP cells.

Coronopilin-another major sesquiterpene lactone in Parthenium hysterophorus

No abstract is available.

The Biosynthesis of Sesquiterpene Isocyanides and Isothiocyanates in the Marine Sponge Acanthella cavernosa (Dendy); Evidence for Dietary Transfer to the Dorid Nudibranch Phyllidiella pustulosa

The tropical marine sponge Acanthella cavernosa (Dendy) converts potassium [14C] cyanide to axisonitrile-3 (1); this precursor is also used for the synthesis of axisothiocyanate-3 (2) suggesting that isocyanides are precursors to isothiocyanates in A. cavernosa. Likewise, potassium [14C] thiocyanate is used for the synthesis of axisothiocyanate-3; unexpectedly this precursor also labelled axisonitrile-3. These results demonstrate either an interconversion between cyanide and thiocyanate prior to secondary metabolite formation or that the secondary metabolites can themselves be interconverted. Specimens of the dorid nudibranch Phyllidiellu pustulosa, preadapted to a diet of A. cavernosa, fed on 14C-labelled sponges and were subsequently found to contain the radioactive terpenes (1) and (2). Specimens of P. pustulosa, which had not expressed a dietary preference for A. cavernosa in the field, did not generally feed in aquarium tests with 14C-labelled sponges and, therefore, provided non-radioactive extracts. Since control experiments demonstrated the inability of P. pustulosa to synthesise the metabolites de novo, we therefore conclude that P. pustulosa acquires secondary metabolites by dietary transfer from A. cavernosa.

Pyrrolizidine Alkaloids in Crotalaria Taxa from Northern Australia: Risk to Grazing Livestock.

Crotalaria species containing hepatotoxic pyrrolizidine alkaloids grow widely in pastures in northern Australia and have sporadically poisoned grazing livestock. The diverse Crotalaria taxa present in these pastures include varieties, subspecies, and chemotypes not previously chemically examined. This paper reports the pyrrolizidine alkaloid composition and content of 24 Crotalaria taxa from this region and assesses the risk of poisoning in livestock consuming them. Alkaloids present in C. goreensis, C. aridicola subsp. densifolia, and C. medicaginea var. neglecta lack the esterified 1,2-unsaturated functionality required for pyrrole adduct formation, and these taxa are not hepatotoxic. Taxa with high levels of hepatotoxic alkaloids, abundance, and biomass pose the greatest risk to livestock health, particularly C. novae-hollandiae subsp. novae-hollandiae, C. ramosissima, C. retusa var. retusa, and C. crispata. Other species containing moderate alkaloid levels, C. spectabilis and C. mitchellii, also pose significant risk when locally abundant.

Risks from plants containing pyrrolizidine alkaloids for livestock and meat quality in Northern Australia.

This chapter describes poisoning associated with consumption of pyrrolizidine alkaloid (PA)-containing plants (Crotalaria spp., Heliotropium spp. and Senecio spp.) by cattle and horses in rangelands of northern Australia, as well as the risks for meat quality of PA residues and potential health hazards to consumers.

Studies in sesquiterpenes-XVI. Zerumbone, a monocyclic sesquiterpene ketone

The structure, previously assigned to zerumbone, has been found to be untenable. The ketone has been shown to be monocyclic containing three ethylenic linkages, and has been further correlated with humulene. Results from ozonolysis, and base-catalysed cleavage allowed the compound to be formulated as 2,6,9,9-tetramethyl-2,6,10-cyclo-undecatrien-1-one.

Synthesis, structure and DNA cleavage studies of coumarin analogues of tetrahydroisoquinoline and protoberberine alkaloids

Novel molecular matrices have been derived from coumarin-4-acetic acids and beta-phenylethylamines using the Bischler-Napieralski protocol which has led to the synthesis of analogues of tetrahydropapaverine in which the dimethoxybenzene moiety has been replaced by substituted coumarins. One carbon homologation has led to cyclization at the C3 position of coumarin generating the protoberberine skeleton. Structures have been confirmed by diffraction studies. The results showed that compounds 6e, 6f, 7e and 7f were found to be very effective against DNA samples of Gram positive bacterium Staphylococcus aureus and fungus Aspergillus niger. (C) 2010 Elsevier Masson SAS. All rights reserved.

Alkaloid synthesis: stereoselective approach towards fawcettimine-serratinine group of lycopodium alkaloids

The concept of carbocycle-heterocycle equivalency has been utilised to assemble the framework of fawcettimine-serratinine group of alkaloids from 1,5-cyclooctadiene through a common tricarbocyclic intermediate 3.