Murray Munro - Academia.edu (original) (raw)

Papers by Murray Munro

Research paper thumbnail of Interactions of Halichondrin B and Eribulin with Tubulin

Journal of Chemical Information and Modeling, May 13, 2011

Compounds that modulate microtubule dynamics include highly effective anticancer drugs, leading t... more Compounds that modulate microtubule dynamics include highly effective anticancer drugs, leading to continuing efforts to identify new agents and improve the activity of established ones. Here, we demonstrate that [ 3 H]-labeled halichondrin B (HB), a complex, sponge-derived natural product, is bound to and dissociated from tubulin rapidly at one binding site per αβ-heterodimer, with an apparent K d of 0.31 μM. We found no HB-induced aggregation of tubulin by highperformance liquid chromatography, even following column equilibration with HB. Binding of [ 3 H]HB was competitively inhibited by a newly approved clinical agent, the truncated HB analogue eribulin (apparent K i , 0.80 μM) and noncompetitively by dolastatin 10 and vincristine (apparent K i 's, 0.35 and 5.4 μM, respectively). Our earlier studies demonstrated that HB inhibits nucleotide exchange on β-tubulin, and this, together with the results presented here, indicated the HB site is located on β-tubulin. Using molecular dynamics simulations, we determined complementary conformations of HB and β-tubulin that delineated in atomic detail binding interactions of HB with only β-tubulin, with no involvement of the α-subunit in the binding interaction. Moreover, the HB model served as a template for an eribulin binding model that furthered our understanding of the properties of eribulin as a drug. Overall, these results established a mechanistic basis for the antimitotic activity of the halichondrin class of compounds.

Research paper thumbnail of Effects of short-term exposure to paralytic shellfish toxins on clearance rates and toxin uptake in five species of New Zealand bivalve

Marine and Freshwater Research, 2012

Algal blooms produced by toxic dinoflagellates have increased worldwide, resulting in economic lo... more Algal blooms produced by toxic dinoflagellates have increased worldwide, resulting in economic losses to aquaculture and fisheries. Bivalve species differ in their ability to feed on toxin-producing dinoflagellates and this could result in differences in toxin accumulation among species. In New Zealand, the effects of paralytic shellfish poisoning (PSP) toxins on the physiology of bivalve molluscs are relatively unknown. We hypothesised that the feeding responses of five New Zealand bivalve species exposed to PSP-toxic dinoflagellates would be species-specific, affecting their accumulation of toxins. Each species was exposed to toxic and non-toxic species of Alexandrium spp. and clearance rate used as an index of sensitivity to PSP toxins. Clearance rates for the mussel Perna canaliculus and the clam Dosinia anus were unaffected by the presence of toxic dinoflagellates, whereas the rate in the scallop Pecten novaezelandiae decreased significantly. There were variable results for the clam Paphies donacina and the oyster Ostrea chilensis. Species-specific biotransformation of PSP-toxins had taken place in the bivalve tissues. We conclude that the rate of accumulation of PSP toxins in the tissues of the bivalve species was influenced by their feeding behaviour and the different chemical processes that had taken place in their tissues.

Research paper thumbnail of 3,4′-Linked bis(piperidines) related to the haliclonacyclamine class of marine alkaloids: synthesis using crossed-aldol chemistry and preliminary biological evaluations

Research paper thumbnail of Effects of short-term exposure to paralytic shellfish toxins on clearance rates and toxin uptake in five species of New Zealand bivalve

Marine and Freshwater Research, 2012

Algal blooms produced by toxic dinoflagellates have increased worldwide, resulting in economic lo... more Algal blooms produced by toxic dinoflagellates have increased worldwide, resulting in economic losses to aquaculture and fisheries. Bivalve species differ in their ability to feed on toxin-producing dinoflagellates and this could result in differences in toxin accumulation among species. In New Zealand, the effects of paralytic shellfish poisoning (PSP) toxins on the physiology of bivalve molluscs are relatively unknown. We hypothesised that the feeding responses of five New Zealand bivalve species exposed to PSP-toxic dinoflagellates would be species-specific, affecting their accumulation of toxins. Each species was exposed to toxic and non-toxic species of Alexandrium spp. and clearance rate used as an index of sensitivity to PSP toxins. Clearance rates for the mussel Perna canaliculus and the clam Dosinia anus were unaffected by the presence of toxic dinoflagellates, whereas the rate in the scallop Pecten novaezelandiae decreased significantly. There were variable results for the...

Research paper thumbnail of Chrysosporide, a Cyclic Pentapeptide from a New Zealand Sample of the Fungus Sepedonium chrysospermum

Chrysosporide, a Cyclic Pentapeptide from a New Zealand Sample of the Fungus Sepedonium chrysospermum

Journal of Natural Products, 2006

A new cyclic pentapeptide, chrysosporide (1), was isolated from a New Zealand sample of the mycop... more A new cyclic pentapeptide, chrysosporide (1), was isolated from a New Zealand sample of the mycoparasitic fungus Sepedonium chrysospermum by bioactivity-guided fractionation. The planar structure was deduced by detailed spectroscopic analysis, and the absolute configurations of the amino acid residues were defined by Marfey's method. As both enantiomers of Leu occurred in chrysosporide, molecular mechanics calculations were applied to the analysis to distinguish between the possible structural isomers. Only the lowest energy conformers of the cyclo-(L-Val-D-Ala-L-Leu-L-Leu-D-Leu) isomer were in agreement with the observed NOEs, suggesting that this was the most probable amino acid sequence for chrysosporide (1).

Research paper thumbnail of Interactions of Halichondrin B and Eribulin with Tubulin

Journal of Chemical Information and Modeling, 2011

Compounds that modulate microtubule dynamics include highly effective anticancer drugs, leading t... more Compounds that modulate microtubule dynamics include highly effective anticancer drugs, leading to continuing efforts to identify new agents and improve the activity of established ones. Here, we demonstrate that [ 3 H]-labeled halichondrin B (HB), a complex, sponge-derived natural product, is bound to and dissociated from tubulin rapidly at one binding site per αβ-heterodimer, with an apparent K d of 0.31 μM. We found no HB-induced aggregation of tubulin by highperformance liquid chromatography, even following column equilibration with HB. Binding of [ 3 H]HB was competitively inhibited by a newly approved clinical agent, the truncated HB analogue eribulin (apparent K i , 0.80 μM) and noncompetitively by dolastatin 10 and vincristine (apparent K i 's, 0.35 and 5.4 μM, respectively). Our earlier studies demonstrated that HB inhibits nucleotide exchange on β-tubulin, and this, together with the results presented here, indicated the HB site is located on β-tubulin. Using molecular dynamics simulations, we determined complementary conformations of HB and β-tubulin that delineated in atomic detail binding interactions of HB with only β-tubulin, with no involvement of the α-subunit in the binding interaction. Moreover, the HB model served as a template for an eribulin binding model that furthered our understanding of the properties of eribulin as a drug. Overall, these results established a mechanistic basis for the antimitotic activity of the halichondrin class of compounds.

Research paper thumbnail of Marine natural products

Marine natural products

Annual Reports Section "B" (Organic Chemistry), 2008

Research paper thumbnail of Marine natural products

Natural Product Reports, 2005

This review covers the literature published in 2003 for marine natural products, with 619 citatio... more This review covers the literature published in 2003 for marine natural products, with 619 citations (413 for the period January to December 2003) referring to compounds isolated from marine microorganisms and phytoplankton, green algae, brown algae, red algae, sponges, coelenterates, bryozoans, molluscs, tunicates and echinoderms. The emphasis is on new compounds (656 for 2003), together with their relevant biological activities, source organisms and country of origin. Biosynthetic studies or syntheses that lead to the revision of structures or stereochemistries have been included (78), including any first total syntheses of a marine natural product. 3 Marine microorganisms and phytoplankton 4 Green algae 5 Brown algae 6 Red algae 7 Sponges 8 Coelenterates 9 Bryozoans 10 Molluscs 11 Tunicates (ascidians) 12 Echinoderms 13 Miscellaneous 14 Conclusions 15 Acknowledgements 16 References 2 Reviews A number of reviews have dealt with classes of compounds: "Sterols in microorganisms", 1 "Bioactive macrolides and polyketides from marine dinoflagellates", 2 "Chemistry and biology of new marine alkaloids from the indole and annelated indole series", 3 "Brominated diterpenes of marine origin", 4 "Sulfur-containing natural products from marine invertebrates", 5 "The cerebrosides", 6 "Nonribosomal peptides from marine sponges", 7 "Bioactive polyhydroxysterols and their sapogenins from marine organisms", 8 "Sphingolipids from marine organisms", 9 "A review of research on the cyanotoxin cylindrospermopsin", 10 and "The manzamine alkaloids". 11 Reviews that focus on bioactivity and development as drug candidates include: "Natural products as sources of new drugs over the period 1981-2002", 12 "Marine natural products as prototype agrochemical agents", 13 "Detection of pharmacologically active natural products using ecology", 14 "Marine pharmacology in 2000: antitumour and cytotoxic compounds", 15 "Bioactive natural products from marine invertebrates and associated fungi", 16 "Marine pyridoacridine alkaloids and synthetic analogues as antitumour agents", 17 "Drugs from the deep: marine natural products as drug candidates", 18 "Marine-derived anticancer agents in clinical trials", 19 "Marine natural products as lead anti-HIV agents", 20 "Natural products with anti-HIV activity from marine organisms", 21 "Algae, a possible source for new drugs in the treatment of HIV and other viral diseases", 22 and "Antimycobacterial natural products". 23 Chemical synthesis is the theme of a number of reviews covering specific types of compounds through to more generally applicable methodology: "Total synthesis of (+)macrosphelides A, C, E, F and G based on enzymatic function", 24 "The total syntheses of phorboxazoles-new classes in natural product synthesis", 25 "The development of a practical total synthesis of discodermolide", 26 "Synthesis of the pyrrole-imidazole alkaloids", 27 "Chemistry of bisspiroacetal systems: natural products, synthesis and stereochemistry", 28 "Approaches towards the

Research paper thumbnail of Biological activity in New Zealand marine organisms

Pure and Applied Chemistry, 1989

The incidence and significance of antiviral and cytotoxic activity in a New Zealand collection of... more The incidence and significance of antiviral and cytotoxic activity in a New Zealand collection of marine organisms has been investigated. Several compounds with potent biological activities have been isolated and characterised.

Research paper thumbnail of A general synthesis of the acarnidines

Tetrahedron Letters, 1982

Research paper thumbnail of Application of a selective method in the search for new bioactive natural products from fungi

Application of a selective method in the search for new bioactive natural products from fungi

Planta Medica, 2008

Research paper thumbnail of spiro-Mamakone A:  A Unique Relative of the Spirobisnaphthalene Class of Compounds

spiro-Mamakone A: A Unique Relative of the Spirobisnaphthalene Class of Compounds

Organic Letters, 2006

[structure: see text] A spirobisnaphthalene derivative with a new spiro-nonadiene skeleton, spiro... more [structure: see text] A spirobisnaphthalene derivative with a new spiro-nonadiene skeleton, spiro-mamakone A (1), has been isolated from the extract of a cultured nonsporulating fungal endophyte derived from the New Zealand native tree Knightia excelsa (rewarewa). The carbon skeleton of spiro-mamakone A represents a new structural entity and an intriguing addition to the structurally diverse spirobisnaphthalene group of compounds. spiro-Mamakone A is potently cytotoxic and is also antimicrobial.

Research paper thumbnail of Synthetic and biological studies on the spiro-mamakone system

Organic & Biomolecular Chemistry, 2008

Research paper thumbnail of Pteratides I−IV, New Cytotoxic Cyclodepsipeptides from the Malaysian Basidiomycete Pterula sp

The Journal of Organic Chemistry, 2006

Research paper thumbnail of An Unusual Oxalylated Tetramic Acid from the New Zealand Basidiomycete Chamonixia pachydermis

Journal of Natural Products, 2006

An unusual oxalylated tetramic acid, pachydermin (1), has been isolated from the New Zealand basi... more An unusual oxalylated tetramic acid, pachydermin (1), has been isolated from the New Zealand basidiomycete Chamonixia pachydermis. The full structure, which was not directly accessible by NMR methods, was deduced from that of a degradation product, 5-(3-chloro-4-hydroxybenzylidene)tetramic acid (2). The degradation product 2 exhibited mild antibacterial activity against Bacillus subtilis.

Research paper thumbnail of Dichlorinated Pulvinic Acid Derivative from a Malaysian Scleroderma sp

Dichlorinated Pulvinic Acid Derivative from a Malaysian Scleroderma sp

Journal of Natural Products, 2005

A new dichlorinated pulvinic acid derivative, methyl-3&am... more A new dichlorinated pulvinic acid derivative, methyl-3',5'-dichloro-4,4'-di-O-methylatromentate, was isolated from the fruiting body of a Scleroderma sp. The structure was determined using spectroscopic methods, and an X-ray analysis was carried out for confirmation of the structure. Compound was found to display moderate antimicrobial activity against Bacillus subtilis.

Research paper thumbnail of Lanostane Triterpenoids from the Sri Lankan Basidiomycete Ganoderma applanatum

Lanostane Triterpenoids from the Sri Lankan Basidiomycete Ganoderma applanatum

Journal of Natural Products, 2006

Two new lanostane-type triterpenoids, 3alpha,16alpha-dihydroxylanosta-7,9(11),24-trien-21-oic aci... more Two new lanostane-type triterpenoids, 3alpha,16alpha-dihydroxylanosta-7,9(11),24-trien-21-oic acid (1) and 3alpha,16alpha,26-trihydroxylanosta-7,9(11),24-trien-21-oic acid (2), along with three known lanostanoids, 16alpha-hydroxy-3-oxolanosta-7,9(11),24-trien-21-oic acid (3), 3alpha-carboxyacetoxy-24-methylen-23-oxolanost-8-en-26-oic acid (4), and 3alpha-carboxyacetoxy-24-methyl-23-oxolanost-8-en-26-oic acid (5), have been isolated from the EtOAc extract of the fruiting body of Ganoderma applanatum. The structures of 1, 2, and 3 were determined directly by the interpretation of spectroscopic data, while the structures of 4 and 5 were assigned by comparison of spectroscopic data against literature values.

Research paper thumbnail of Pterulamides I−VI, Linear Peptides from a Malaysian Pterula sp

Journal of Natural Products, 2006

Six new linear peptides, pterulamides I-VI (1-6), were isolated from the fruiting bodies of a Mal... more Six new linear peptides, pterulamides I-VI (1-6), were isolated from the fruiting bodies of a Malaysian Pterula species. The structures were elucidated by MS and 2D NMR experiments, and the absolute configurations of the constituent amino acids established using Marfey's method. The pterulamides are mainly assembled from nonpolar N-methylated amino acids and, most interestingly, have non-amino-acid N-terminal groups, among them the unusual cinnamoyl, (E)-3-methylsulfinylpropenoyl, and (E)-3-methylthiopropenoyl groups. Furthermore, pterulamides I-V are the first natural peptides with a methylamide C-terminus. Pterulamides I and IV are cytotoxic against the P388 cell line with IC 50 values of 0.55 and 0.95 µg/mL (0.79 and 1.33 µM), respectively. Fungi of the genus Pterula (family Clavariaceae) are clavarioid basidiomycetes with predominantly coral-shaped fruiting bodies. A great variety of Pterula species occur from temperate to tropical regions, 1 but relatively little is known about the chemistry of these fungi. The only strain investigated, Pterula sp. 82168, was shown to produce the previously unknown natural products hydroxystrobilurin A, 2 pterulones A and B, 3,4 pterulinic acid, 3 and noroudemansin A, 5 all of which were strongly bioactive. In this paper we describe the isolation, structural elucidation, and biological activities of six novel linear peptides, pterulamides I-VI (1-6), from the fruiting bodies of a Malaysian Pterula sp. These compounds are remarkable not only for their high degree of N-methylation but because they also contain unusual, or unprecedented, N-terminal groups, viz., benzoyl, cinnamoyl, (E)-3methylsulfinylpropenoyl, and (E)-3-methylthiopropenoyl. A further structural feature hitherto unknown from natural peptides is the methylamide C-terminus found in pterulamides I-V.

Research paper thumbnail of Concise, Stereoselective Route to the Four Diastereoisomers of 4-Methylproline

Journal of Natural Products, 2008

A general and practical synthetic process for all the four diastereoisomers of Boc-protected 4met... more A general and practical synthetic process for all the four diastereoisomers of Boc-protected 4methylproline carboxylates has been developed with essentially complete stereoselectivity on the gram scale, which represents the most diastereoselective preparation of 4-methylproline derivatives to date. This synthesis features an Evans asymmetric alkylation to elegantly establish the challenging stereochemistry of the 4-methyl group, providing valuable insights for the diastereoselective preparation of 4-substituted prolines.

Research paper thumbnail of Cytotoxic and Antifungal Activities of 5-Hydroxyramulosin, a Compound Produced by an Endophytic Fungus Isolated fromCinnamomum mollisimum

Evidence-Based Complementary and Alternative Medicine, 2012

An endophytic fungus isolated from the plantCinnamomum mollissimumwas investigated for the bioact... more An endophytic fungus isolated from the plantCinnamomum mollissimumwas investigated for the bioactivity of its metabolites. The fungus, similar to aPhomasp., was cultured in potato dextrose broth for two weeks, followed by extraction with ethyl acetate. The crude extract obtained was fractionated by high-performance liquid chromatography. Both crude extract and fractions were assayed for cytotoxicity against P388 murine leukemic cells and inhibition of bacterial and fungal pathogens. The bioactive extract fraction was purified further and characterized by nuclear magnetic resonance, mass spectral and X-ray crystallography analysis. A polyketide compound, 5-hydroxyramulosin, was identified as the constituent of the bioactive fungal extract fraction. This compound inhibited the fungal pathogenAspergillus niger(IC501.56 μg/mL) and was cytotoxic against murine leukemia cells (IC502.10 μg/mL). 5-Hydroxyramulosin was the major compound produced by the endophytic fungus. This research sugge...

Research paper thumbnail of Interactions of Halichondrin B and Eribulin with Tubulin

Journal of Chemical Information and Modeling, May 13, 2011

Compounds that modulate microtubule dynamics include highly effective anticancer drugs, leading t... more Compounds that modulate microtubule dynamics include highly effective anticancer drugs, leading to continuing efforts to identify new agents and improve the activity of established ones. Here, we demonstrate that [ 3 H]-labeled halichondrin B (HB), a complex, sponge-derived natural product, is bound to and dissociated from tubulin rapidly at one binding site per αβ-heterodimer, with an apparent K d of 0.31 μM. We found no HB-induced aggregation of tubulin by highperformance liquid chromatography, even following column equilibration with HB. Binding of [ 3 H]HB was competitively inhibited by a newly approved clinical agent, the truncated HB analogue eribulin (apparent K i , 0.80 μM) and noncompetitively by dolastatin 10 and vincristine (apparent K i 's, 0.35 and 5.4 μM, respectively). Our earlier studies demonstrated that HB inhibits nucleotide exchange on β-tubulin, and this, together with the results presented here, indicated the HB site is located on β-tubulin. Using molecular dynamics simulations, we determined complementary conformations of HB and β-tubulin that delineated in atomic detail binding interactions of HB with only β-tubulin, with no involvement of the α-subunit in the binding interaction. Moreover, the HB model served as a template for an eribulin binding model that furthered our understanding of the properties of eribulin as a drug. Overall, these results established a mechanistic basis for the antimitotic activity of the halichondrin class of compounds.

Research paper thumbnail of Effects of short-term exposure to paralytic shellfish toxins on clearance rates and toxin uptake in five species of New Zealand bivalve

Marine and Freshwater Research, 2012

Algal blooms produced by toxic dinoflagellates have increased worldwide, resulting in economic lo... more Algal blooms produced by toxic dinoflagellates have increased worldwide, resulting in economic losses to aquaculture and fisheries. Bivalve species differ in their ability to feed on toxin-producing dinoflagellates and this could result in differences in toxin accumulation among species. In New Zealand, the effects of paralytic shellfish poisoning (PSP) toxins on the physiology of bivalve molluscs are relatively unknown. We hypothesised that the feeding responses of five New Zealand bivalve species exposed to PSP-toxic dinoflagellates would be species-specific, affecting their accumulation of toxins. Each species was exposed to toxic and non-toxic species of Alexandrium spp. and clearance rate used as an index of sensitivity to PSP toxins. Clearance rates for the mussel Perna canaliculus and the clam Dosinia anus were unaffected by the presence of toxic dinoflagellates, whereas the rate in the scallop Pecten novaezelandiae decreased significantly. There were variable results for the clam Paphies donacina and the oyster Ostrea chilensis. Species-specific biotransformation of PSP-toxins had taken place in the bivalve tissues. We conclude that the rate of accumulation of PSP toxins in the tissues of the bivalve species was influenced by their feeding behaviour and the different chemical processes that had taken place in their tissues.

Research paper thumbnail of 3,4′-Linked bis(piperidines) related to the haliclonacyclamine class of marine alkaloids: synthesis using crossed-aldol chemistry and preliminary biological evaluations

Research paper thumbnail of Effects of short-term exposure to paralytic shellfish toxins on clearance rates and toxin uptake in five species of New Zealand bivalve

Marine and Freshwater Research, 2012

Algal blooms produced by toxic dinoflagellates have increased worldwide, resulting in economic lo... more Algal blooms produced by toxic dinoflagellates have increased worldwide, resulting in economic losses to aquaculture and fisheries. Bivalve species differ in their ability to feed on toxin-producing dinoflagellates and this could result in differences in toxin accumulation among species. In New Zealand, the effects of paralytic shellfish poisoning (PSP) toxins on the physiology of bivalve molluscs are relatively unknown. We hypothesised that the feeding responses of five New Zealand bivalve species exposed to PSP-toxic dinoflagellates would be species-specific, affecting their accumulation of toxins. Each species was exposed to toxic and non-toxic species of Alexandrium spp. and clearance rate used as an index of sensitivity to PSP toxins. Clearance rates for the mussel Perna canaliculus and the clam Dosinia anus were unaffected by the presence of toxic dinoflagellates, whereas the rate in the scallop Pecten novaezelandiae decreased significantly. There were variable results for the...

Research paper thumbnail of Chrysosporide, a Cyclic Pentapeptide from a New Zealand Sample of the Fungus Sepedonium chrysospermum

Chrysosporide, a Cyclic Pentapeptide from a New Zealand Sample of the Fungus Sepedonium chrysospermum

Journal of Natural Products, 2006

A new cyclic pentapeptide, chrysosporide (1), was isolated from a New Zealand sample of the mycop... more A new cyclic pentapeptide, chrysosporide (1), was isolated from a New Zealand sample of the mycoparasitic fungus Sepedonium chrysospermum by bioactivity-guided fractionation. The planar structure was deduced by detailed spectroscopic analysis, and the absolute configurations of the amino acid residues were defined by Marfey's method. As both enantiomers of Leu occurred in chrysosporide, molecular mechanics calculations were applied to the analysis to distinguish between the possible structural isomers. Only the lowest energy conformers of the cyclo-(L-Val-D-Ala-L-Leu-L-Leu-D-Leu) isomer were in agreement with the observed NOEs, suggesting that this was the most probable amino acid sequence for chrysosporide (1).

Research paper thumbnail of Interactions of Halichondrin B and Eribulin with Tubulin

Journal of Chemical Information and Modeling, 2011

Compounds that modulate microtubule dynamics include highly effective anticancer drugs, leading t... more Compounds that modulate microtubule dynamics include highly effective anticancer drugs, leading to continuing efforts to identify new agents and improve the activity of established ones. Here, we demonstrate that [ 3 H]-labeled halichondrin B (HB), a complex, sponge-derived natural product, is bound to and dissociated from tubulin rapidly at one binding site per αβ-heterodimer, with an apparent K d of 0.31 μM. We found no HB-induced aggregation of tubulin by highperformance liquid chromatography, even following column equilibration with HB. Binding of [ 3 H]HB was competitively inhibited by a newly approved clinical agent, the truncated HB analogue eribulin (apparent K i , 0.80 μM) and noncompetitively by dolastatin 10 and vincristine (apparent K i 's, 0.35 and 5.4 μM, respectively). Our earlier studies demonstrated that HB inhibits nucleotide exchange on β-tubulin, and this, together with the results presented here, indicated the HB site is located on β-tubulin. Using molecular dynamics simulations, we determined complementary conformations of HB and β-tubulin that delineated in atomic detail binding interactions of HB with only β-tubulin, with no involvement of the α-subunit in the binding interaction. Moreover, the HB model served as a template for an eribulin binding model that furthered our understanding of the properties of eribulin as a drug. Overall, these results established a mechanistic basis for the antimitotic activity of the halichondrin class of compounds.

Research paper thumbnail of Marine natural products

Marine natural products

Annual Reports Section "B" (Organic Chemistry), 2008

Research paper thumbnail of Marine natural products

Natural Product Reports, 2005

This review covers the literature published in 2003 for marine natural products, with 619 citatio... more This review covers the literature published in 2003 for marine natural products, with 619 citations (413 for the period January to December 2003) referring to compounds isolated from marine microorganisms and phytoplankton, green algae, brown algae, red algae, sponges, coelenterates, bryozoans, molluscs, tunicates and echinoderms. The emphasis is on new compounds (656 for 2003), together with their relevant biological activities, source organisms and country of origin. Biosynthetic studies or syntheses that lead to the revision of structures or stereochemistries have been included (78), including any first total syntheses of a marine natural product. 3 Marine microorganisms and phytoplankton 4 Green algae 5 Brown algae 6 Red algae 7 Sponges 8 Coelenterates 9 Bryozoans 10 Molluscs 11 Tunicates (ascidians) 12 Echinoderms 13 Miscellaneous 14 Conclusions 15 Acknowledgements 16 References 2 Reviews A number of reviews have dealt with classes of compounds: "Sterols in microorganisms", 1 "Bioactive macrolides and polyketides from marine dinoflagellates", 2 "Chemistry and biology of new marine alkaloids from the indole and annelated indole series", 3 "Brominated diterpenes of marine origin", 4 "Sulfur-containing natural products from marine invertebrates", 5 "The cerebrosides", 6 "Nonribosomal peptides from marine sponges", 7 "Bioactive polyhydroxysterols and their sapogenins from marine organisms", 8 "Sphingolipids from marine organisms", 9 "A review of research on the cyanotoxin cylindrospermopsin", 10 and "The manzamine alkaloids". 11 Reviews that focus on bioactivity and development as drug candidates include: "Natural products as sources of new drugs over the period 1981-2002", 12 "Marine natural products as prototype agrochemical agents", 13 "Detection of pharmacologically active natural products using ecology", 14 "Marine pharmacology in 2000: antitumour and cytotoxic compounds", 15 "Bioactive natural products from marine invertebrates and associated fungi", 16 "Marine pyridoacridine alkaloids and synthetic analogues as antitumour agents", 17 "Drugs from the deep: marine natural products as drug candidates", 18 "Marine-derived anticancer agents in clinical trials", 19 "Marine natural products as lead anti-HIV agents", 20 "Natural products with anti-HIV activity from marine organisms", 21 "Algae, a possible source for new drugs in the treatment of HIV and other viral diseases", 22 and "Antimycobacterial natural products". 23 Chemical synthesis is the theme of a number of reviews covering specific types of compounds through to more generally applicable methodology: "Total synthesis of (+)macrosphelides A, C, E, F and G based on enzymatic function", 24 "The total syntheses of phorboxazoles-new classes in natural product synthesis", 25 "The development of a practical total synthesis of discodermolide", 26 "Synthesis of the pyrrole-imidazole alkaloids", 27 "Chemistry of bisspiroacetal systems: natural products, synthesis and stereochemistry", 28 "Approaches towards the

Research paper thumbnail of Biological activity in New Zealand marine organisms

Pure and Applied Chemistry, 1989

The incidence and significance of antiviral and cytotoxic activity in a New Zealand collection of... more The incidence and significance of antiviral and cytotoxic activity in a New Zealand collection of marine organisms has been investigated. Several compounds with potent biological activities have been isolated and characterised.

Research paper thumbnail of A general synthesis of the acarnidines

Tetrahedron Letters, 1982

Research paper thumbnail of Application of a selective method in the search for new bioactive natural products from fungi

Application of a selective method in the search for new bioactive natural products from fungi

Planta Medica, 2008

Research paper thumbnail of spiro-Mamakone A:  A Unique Relative of the Spirobisnaphthalene Class of Compounds

spiro-Mamakone A: A Unique Relative of the Spirobisnaphthalene Class of Compounds

Organic Letters, 2006

[structure: see text] A spirobisnaphthalene derivative with a new spiro-nonadiene skeleton, spiro... more [structure: see text] A spirobisnaphthalene derivative with a new spiro-nonadiene skeleton, spiro-mamakone A (1), has been isolated from the extract of a cultured nonsporulating fungal endophyte derived from the New Zealand native tree Knightia excelsa (rewarewa). The carbon skeleton of spiro-mamakone A represents a new structural entity and an intriguing addition to the structurally diverse spirobisnaphthalene group of compounds. spiro-Mamakone A is potently cytotoxic and is also antimicrobial.

Research paper thumbnail of Synthetic and biological studies on the spiro-mamakone system

Organic & Biomolecular Chemistry, 2008

Research paper thumbnail of Pteratides I−IV, New Cytotoxic Cyclodepsipeptides from the Malaysian Basidiomycete Pterula sp

The Journal of Organic Chemistry, 2006

Research paper thumbnail of An Unusual Oxalylated Tetramic Acid from the New Zealand Basidiomycete Chamonixia pachydermis

Journal of Natural Products, 2006

An unusual oxalylated tetramic acid, pachydermin (1), has been isolated from the New Zealand basi... more An unusual oxalylated tetramic acid, pachydermin (1), has been isolated from the New Zealand basidiomycete Chamonixia pachydermis. The full structure, which was not directly accessible by NMR methods, was deduced from that of a degradation product, 5-(3-chloro-4-hydroxybenzylidene)tetramic acid (2). The degradation product 2 exhibited mild antibacterial activity against Bacillus subtilis.

Research paper thumbnail of Dichlorinated Pulvinic Acid Derivative from a Malaysian Scleroderma sp

Dichlorinated Pulvinic Acid Derivative from a Malaysian Scleroderma sp

Journal of Natural Products, 2005

A new dichlorinated pulvinic acid derivative, methyl-3&am... more A new dichlorinated pulvinic acid derivative, methyl-3',5'-dichloro-4,4'-di-O-methylatromentate, was isolated from the fruiting body of a Scleroderma sp. The structure was determined using spectroscopic methods, and an X-ray analysis was carried out for confirmation of the structure. Compound was found to display moderate antimicrobial activity against Bacillus subtilis.

Research paper thumbnail of Lanostane Triterpenoids from the Sri Lankan Basidiomycete Ganoderma applanatum

Lanostane Triterpenoids from the Sri Lankan Basidiomycete Ganoderma applanatum

Journal of Natural Products, 2006

Two new lanostane-type triterpenoids, 3alpha,16alpha-dihydroxylanosta-7,9(11),24-trien-21-oic aci... more Two new lanostane-type triterpenoids, 3alpha,16alpha-dihydroxylanosta-7,9(11),24-trien-21-oic acid (1) and 3alpha,16alpha,26-trihydroxylanosta-7,9(11),24-trien-21-oic acid (2), along with three known lanostanoids, 16alpha-hydroxy-3-oxolanosta-7,9(11),24-trien-21-oic acid (3), 3alpha-carboxyacetoxy-24-methylen-23-oxolanost-8-en-26-oic acid (4), and 3alpha-carboxyacetoxy-24-methyl-23-oxolanost-8-en-26-oic acid (5), have been isolated from the EtOAc extract of the fruiting body of Ganoderma applanatum. The structures of 1, 2, and 3 were determined directly by the interpretation of spectroscopic data, while the structures of 4 and 5 were assigned by comparison of spectroscopic data against literature values.

Research paper thumbnail of Pterulamides I−VI, Linear Peptides from a Malaysian Pterula sp

Journal of Natural Products, 2006

Six new linear peptides, pterulamides I-VI (1-6), were isolated from the fruiting bodies of a Mal... more Six new linear peptides, pterulamides I-VI (1-6), were isolated from the fruiting bodies of a Malaysian Pterula species. The structures were elucidated by MS and 2D NMR experiments, and the absolute configurations of the constituent amino acids established using Marfey's method. The pterulamides are mainly assembled from nonpolar N-methylated amino acids and, most interestingly, have non-amino-acid N-terminal groups, among them the unusual cinnamoyl, (E)-3-methylsulfinylpropenoyl, and (E)-3-methylthiopropenoyl groups. Furthermore, pterulamides I-V are the first natural peptides with a methylamide C-terminus. Pterulamides I and IV are cytotoxic against the P388 cell line with IC 50 values of 0.55 and 0.95 µg/mL (0.79 and 1.33 µM), respectively. Fungi of the genus Pterula (family Clavariaceae) are clavarioid basidiomycetes with predominantly coral-shaped fruiting bodies. A great variety of Pterula species occur from temperate to tropical regions, 1 but relatively little is known about the chemistry of these fungi. The only strain investigated, Pterula sp. 82168, was shown to produce the previously unknown natural products hydroxystrobilurin A, 2 pterulones A and B, 3,4 pterulinic acid, 3 and noroudemansin A, 5 all of which were strongly bioactive. In this paper we describe the isolation, structural elucidation, and biological activities of six novel linear peptides, pterulamides I-VI (1-6), from the fruiting bodies of a Malaysian Pterula sp. These compounds are remarkable not only for their high degree of N-methylation but because they also contain unusual, or unprecedented, N-terminal groups, viz., benzoyl, cinnamoyl, (E)-3methylsulfinylpropenoyl, and (E)-3-methylthiopropenoyl. A further structural feature hitherto unknown from natural peptides is the methylamide C-terminus found in pterulamides I-V.

Research paper thumbnail of Concise, Stereoselective Route to the Four Diastereoisomers of 4-Methylproline

Journal of Natural Products, 2008

A general and practical synthetic process for all the four diastereoisomers of Boc-protected 4met... more A general and practical synthetic process for all the four diastereoisomers of Boc-protected 4methylproline carboxylates has been developed with essentially complete stereoselectivity on the gram scale, which represents the most diastereoselective preparation of 4-methylproline derivatives to date. This synthesis features an Evans asymmetric alkylation to elegantly establish the challenging stereochemistry of the 4-methyl group, providing valuable insights for the diastereoselective preparation of 4-substituted prolines.

Research paper thumbnail of Cytotoxic and Antifungal Activities of 5-Hydroxyramulosin, a Compound Produced by an Endophytic Fungus Isolated fromCinnamomum mollisimum

Evidence-Based Complementary and Alternative Medicine, 2012

An endophytic fungus isolated from the plantCinnamomum mollissimumwas investigated for the bioact... more An endophytic fungus isolated from the plantCinnamomum mollissimumwas investigated for the bioactivity of its metabolites. The fungus, similar to aPhomasp., was cultured in potato dextrose broth for two weeks, followed by extraction with ethyl acetate. The crude extract obtained was fractionated by high-performance liquid chromatography. Both crude extract and fractions were assayed for cytotoxicity against P388 murine leukemic cells and inhibition of bacterial and fungal pathogens. The bioactive extract fraction was purified further and characterized by nuclear magnetic resonance, mass spectral and X-ray crystallography analysis. A polyketide compound, 5-hydroxyramulosin, was identified as the constituent of the bioactive fungal extract fraction. This compound inhibited the fungal pathogenAspergillus niger(IC501.56 μg/mL) and was cytotoxic against murine leukemia cells (IC502.10 μg/mL). 5-Hydroxyramulosin was the major compound produced by the endophytic fungus. This research sugge...