Search

Sample configurations of distaminolyne A (1a); isolated from the ascidians Pseudodistoma opacum and P. cereum, and collected at different sites in New Zealand, were investigated by two methods: Exciton coupled electronic circular dichroism (EC ECD) of the corresponding N,O-dibenzoyl derivative 1b; and chiral reagent derivatization of 1a with (S)- and (R)-α-methoxyphenylacetic acid (MPA), followed by ¹H-NMR analysis. Configuration and optical purity of 1a (%ee) was found to vary depending on the geographic distribution of ascidian colonies. An improved method for preparing N,O-diarenoyl derivatives of 1a was optimized. The EC ECD method was found to be complementary to the MPA-NMR method at different ranges of %ee.

Sample configurations of distaminolyne A (1a); isolated from the ascidians Pseudodistoma opacum and P. cereum, and collected at different sites in New Zealand, were investigated by two methods: Exciton coupled electronic circular dichroism (EC ECD) of the corresponding N,O-dibenzoyl derivative 1b; and chiral reagent derivatization of 1a with (S)- and (R)-α-methoxyphenylacetic acid (MPA), followed by ¹H-NMR analysis. Configuration and optical purity of 1a (%ee) was found to vary depending on the geographic distribution of ascidian colonies. An improved method for preparing N,O-diarenoyl derivatives of 1a was optimized. The EC ECD method was found to be complementary to the MPA-NMR method at different ranges of %ee.

Research has been conducted on the ascidian-derived alkaloid enantiomeric pair from New Zealand. The enantiomeric nature of these alkaloids has been investigated and the results are presented.

The first total synthesis of (--)-bicubebin A, and two previously unreported dilignans, (--)-bicubebin B and (+)-bicubebin C has been achieved through the dimerization of (--)-cubebin, confirming the structure and absolute stereochemistry of (--)-bicubebin A. Analysis of the data for (--)-bicubebin B showed it matched that of reported compound (--)-cis-cubebin. The NMR data of the subsequently synthesized proposed structure of cis-cubebin confirmed that its original proposed structure was incorrect. [ABSTRACT FROM AUTHOR]

A study of the bioactive crude extract of the New Zealand ascidian Lissoclinum notti led to the isolation of the new pyridoacridine alkaloids isodiplamine (4), cystodytin K (5) and lissoclinidine (6), as well as the known pyridoacridine alkaloids diplamine (7) and cystodytin J (8) and the benzopentathiepin varacin (3) and related trithiane varacin A. The new alkaloids were characterised using standard spectroscopic techniques, including 2D 1H–15N NMR experiments. Pyridoacridine alkaloids 4–8 were assayed for a range of biological activities including antitumour and antibiotic properties. [Copyright &y& Elsevier]

Distomadines A and B, novel tetracyclic guanidine-containing 6-hydroxyquinoline alkaloids were isolated from the New Zealand ascidian Pseudodistoma aureum and characterised by interpretation of spectroscopic data and chemical derivatisation. Distomadine A exhibited mild antifungal activity but failed to exhibit any biological activity in a range of antitumour, cytotoxicity, anti-inflammatory, and antimycobacterial tests. The known methyl esters of fatty acids eicosapentaenoic acid (EPA), docosahexaenoic acid and eicosatetraenoic acid were also identified in the extract with EPA methyl ester exhibiting mild cytotoxicity to a non-malignant cell line. [Copyright &y& Elsevier]

Pure compound screening has identified the dioxothiazino-quinoline-quinone ascidian metabolite ascidiathiazone A (2) to be a moderate growth inhibitor of Trypanosoma brucei rhodesiense (IC₅₀ 3.1 μM) and Plasmodium falciparum (K1 dual drug resistant strain) (IC₅₀ 3.3 μM) while exhibiting low levels of cytotoxicity (L6, IC₅₀ 167 μM). A series of C-7 amide and Δ²(³) analogues were prepared that explored the influence of lipophilicity and oxidation state on observed anti-protozoal activity and selectivity. Little variation in anti-malarial potency was observed (IC₅₀ 0.62-6.5 μM), and no correlation was apparent between anti-malarial and anti-T. brucei activity. Phenethylamide 7e and Δ²(³)-glycine analogue 8k exhibited similar anti-Pf activity to 2 but with slightly enhanced selectivity (SI 72 and 93, respectively), while Δ²(³)-phenethylamide 8e (IC₅₀ 0.67 μM, SI 78) exhibited improved potency and selectivity towards T. brucei rhodesiense compared to the natural product hit. A second series of analogues were prepared that replaced the quinoline ring of 2 with benzofuran or benzothiophene moieties. While esters 10a/10b and 15 were once again found to exhibit cytotoxicity, carboxylic acid analogues exhibited potent anti-Pf activity (IC₅₀ 0.34-0.035 μM) combined with excellent selectivity (SI 560-4000). In vivo evaluation of a furan carboxylic acid analogue against P. berghei was undertaken, demonstrating 85.7% and 47% reductions in parasitaemia with ip or oral dosing respectively.

This review covers natural products (secondary metabolites) with reported growth inhibitory activity towards Mycobacterium tuberculosis or related organisms. Such compounds have been isolated from a variety of sources including terrestrial and marine plants and animals, and microorganisms, with the express intent of identifying novel scaffolds for the development of new antituberculosis agents. The literature from January 2003 to December 2005 (inclusive) is reviewed and 146 references to 353 compounds are cited. The compounds are presented in order of chemical type, namely lipids/fatty acids and simple aromatics, phenolics and quinones, peptides, alkaloids, terpenes (monoterpenoids, diterpenes, sesquiterpenes and triterpenes), steroids and miscellaneous structures.

Bioassay-directed fractionation of extracts of a Synoicum n. sp. ascidian from New Zealand led to the isolation of the principal anti-inflammatory component, which was identified by spectroscopic methods as a new member of the rubrolide family, rubrolide O (1), existing as a mixture of E/Z isomers.