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Pearse McCarron
Biotoxin Metrology, National Research Council Canada, 1411 Oxford Street, Nova Scotia, Halifax B3H 3Z1, Canada

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Journal article
Published: 08 March 2021 in Water Research
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Harmful cyanobacterial blooms, which frequently contain toxic secondary metabolites, are reported in aquatic environments around the world. More than two thousand cyanobacterial secondary metabolites have been reported from diverse sources over the past fifty years. A comprehensive, publically-accessible database detailing these secondary metabolites would facilitate research into their occurrence, functions and toxicological risks. To address this need we created CyanoMetDB, a highly curated, flat-file, openly-accessible database of cyanobacterial secondary metabolites collated from 850 peer-reviewed articles published between 1967 and 2020. CyanoMetDB contains 2010 cyanobacterial metabolites and 99 structurally related compounds. This has nearly doubled the number of entries with complete literature metadata and structural composition information compared to previously available open access databases. The dataset includes microcytsins, cyanopeptolins, other depsipeptides, anabaenopeptins, microginins, aeruginosins, cyclamides, cryptophycins, saxitoxins, spumigins, microviridins, and anatoxins among other metabolite classes. A comprehensive database dedicated to cyanobacterial secondary metabolites facilitates: (1) the detection and dereplication of known cyanobacterial toxins and secondary metabolites; (2) the identification of novel natural products from cyanobacteria; (3) research on biosynthesis of cyanobacterial secondary metabolites, including substructure searches; and (4) the investigation of their abundance, persistence, and toxicity in natural environments.

ACS Style

Martin R. Jones; Ernani Pinto; Mariana A. Torres; Fabiane Dörr; Hanna Mazur-Marzec; Karolina Szubert; Luciana Tartaglione; Carmela Dell'Aversano; Christopher O. Miles; Daniel G. Beach; Pearse McCarron; Kaarina Sivonen; David P. Fewer; Jouni Jokela; Elisabeth M.-L. Janssen. CyanoMetDB, a comprehensive public database of secondary metabolites from cyanobacteria. Water Research 2021, 196, 117017 .

AMA Style

Martin R. Jones, Ernani Pinto, Mariana A. Torres, Fabiane Dörr, Hanna Mazur-Marzec, Karolina Szubert, Luciana Tartaglione, Carmela Dell'Aversano, Christopher O. Miles, Daniel G. Beach, Pearse McCarron, Kaarina Sivonen, David P. Fewer, Jouni Jokela, Elisabeth M.-L. Janssen. CyanoMetDB, a comprehensive public database of secondary metabolites from cyanobacteria. Water Research. 2021; 196 ():117017.

Chicago/Turabian Style

Martin R. Jones; Ernani Pinto; Mariana A. Torres; Fabiane Dörr; Hanna Mazur-Marzec; Karolina Szubert; Luciana Tartaglione; Carmela Dell'Aversano; Christopher O. Miles; Daniel G. Beach; Pearse McCarron; Kaarina Sivonen; David P. Fewer; Jouni Jokela; Elisabeth M.-L. Janssen. 2021. "CyanoMetDB, a comprehensive public database of secondary metabolites from cyanobacteria." Water Research 196, no. : 117017.

Research paper
Published: 04 March 2021 in Analytical and Bioanalytical Chemistry
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A freeze-dried mussel tissue–certified reference material (CRM-FDMT1) was prepared containing the marine algal toxin classes azaspiracids, okadaic acid and dinophysistoxins, yessotoxins, pectenotoxins, cyclic imines, and domoic acid. Thus far, only a limited number of analogues in CRM-FDMT1 have been assigned certified values; however, the complete toxin profile is significantly more complex. Liquid chromatography–high-resolution mass spectrometry was used to profile CRM-FDMT1. Full-scan data was searched against a list of previously reported toxin analogues, and characteristic product ions extracted from all-ion-fragmentation data were used to guide the extent of toxin profiling. A series of targeted and untargeted acquisition MS/MS experiments were then used to collect spectra for analogues. A number of toxins previously reported in the literature but not readily available as standards were tentatively identified including dihydroxy and carboxyhydroxyyessotoxin, azaspiracids-33 and -39, sulfonated pectenotoxin analogues, spirolide variants, and fatty acid acyl esters of okadaic acid and pectenotoxins. Previously unreported toxins were also observed including compounds from the pectenotoxin, azaspiracid, yessotoxin, and spirolide classes. More than one hundred toxin analogues present in CRM-FDMT1 are summarized along with a demonstration of the major acyl ester conjugates of several toxins. Retention index values were assigned for all confirmed or tentatively identified analogues to help with qualitative identification of the broad range of lipophilic toxins present in the material.

ACS Style

Elliott J. Wright; Pearse McCarron. A mussel tissue certified reference material for multiple phycotoxins. Part 5: profiling by liquid chromatography–high-resolution mass spectrometry. Analytical and Bioanalytical Chemistry 2021, 413, 2055 -2069.

AMA Style

Elliott J. Wright, Pearse McCarron. A mussel tissue certified reference material for multiple phycotoxins. Part 5: profiling by liquid chromatography–high-resolution mass spectrometry. Analytical and Bioanalytical Chemistry. 2021; 413 (8):2055-2069.

Chicago/Turabian Style

Elliott J. Wright; Pearse McCarron. 2021. "A mussel tissue certified reference material for multiple phycotoxins. Part 5: profiling by liquid chromatography–high-resolution mass spectrometry." Analytical and Bioanalytical Chemistry 413, no. 8: 2055-2069.

Journal article
Published: 28 September 2020 in Toxicon: X
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Azaspiracids (AZAs) are lipophilic polyether toxins produced by Azadinium and Amphidoma species of marine microalgae. The main dinoflagellate precursors AZA1 and AZA2 are metabolized by shellfish to produce an array of AZA analogues. Many marine toxins undergo fatty acid esterification in shellfish, therefore mussel tissues contaminated with AZAs were screened for intact fatty acid esters of AZAs using liquid chromatography-high resolution mass spectrometry. Acyl esters were primarily observed for AZAs containing hydroxy groups at C-3 with 3-O-palmitoylAZA4 identified as the most abundant acyl ester, while other fatty acid esters including 18:1, 16:1, 17:0, 20:2 and 18:0 acyl esters were detected. The structures of these acyl derivatives were determined through LC-MS/MS experiments, and supported by periodate cleavage reactions and semi-synthesis of palmitate esters of the AZAs. Esters of the hydroxy groups at C-20 or C-21 were not observed in mussel tissue. The relative proportion of the most abundant AZA ester was less than 3% of the sum of the major free AZA analogues in the hepatopancreas tissue. These findings reveal an additional metabolic pathway for AZAs in shellfish.

ACS Style

Elizabeth M. Mudge; Christopher O. Miles; William R. Hardstaff; Pearse McCarron. Fatty acid esters of azaspiracids identified in mussels (Mytilus edulis) using liquid chromatography-high resolution mass spectrometry. Toxicon: X 2020, 8, 100059 .

AMA Style

Elizabeth M. Mudge, Christopher O. Miles, William R. Hardstaff, Pearse McCarron. Fatty acid esters of azaspiracids identified in mussels (Mytilus edulis) using liquid chromatography-high resolution mass spectrometry. Toxicon: X. 2020; 8 ():100059.

Chicago/Turabian Style

Elizabeth M. Mudge; Christopher O. Miles; William R. Hardstaff; Pearse McCarron. 2020. "Fatty acid esters of azaspiracids identified in mussels (Mytilus edulis) using liquid chromatography-high resolution mass spectrometry." Toxicon: X 8, no. : 100059.

Research article
Published: 02 September 2020 in Rapid Communications in Mass Spectrometry
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RATIONALE Anatoxins (ATXs) are a potent class of cyanobacterial neurotoxins that are increasingly problematic in drinking water reservoirs and recreational water bodies worldwide. Because of their high polarity and low molecular weight, analysis of ATXs is challenging and they can be considered underreported compared with other classes of cyanobacterial toxins. Improved screening methods are therefore needed to effectively assess their occurrence and concentrations in the environment. METHODS A rapid screening method was developed for ATXs in cyanobacteria using direct analysis in real time – high resolution mass spectrometry (DART–HRMS), requiring < 2 min per sample for triplicate analysis. The developed method was evaluated for its quantitative capabilities, applied to the screening of 30 cyanobacteria culture samples for the presence of anatoxin‐a, homoanatoxin‐a and dihydroanatoxin‐a, and compared with a more typical liquid chromatography–HRMS method. RESULTS Excellent linearity was observed in the analysis of a matrix‐matched calibration curve by DART–HRMS, with ionization suppression of about 50% and relative standard deviations between replicate analyses of approximately 30%. Limits of detection for both anatoxin‐a and homoanatoxin‐a were estimated as 1 ng/mL. Excellent agreement was observed between DART‐HRMS and LC/HRMS with all ATX‐producing cultures correctly identified and only one false positive culture by DART‐HRMS. CONCLUSIONS DART‐HRMS shows excellent promise for the rapid, quantitative screening of ATXs in cyanobacteria and could be expanded in the future to include the analysis of field samples and drinking water, as well as additional ATX analogues.

ACS Style

Daniel G. Beach; Cheryl Rafuse; Jeremy E. Melanson; Pearse McCarron. Rapid quantitative screening of cyanobacteria for production of anatoxins using direct analysis in real time high‐resolution mass spectrometry. Rapid Communications in Mass Spectrometry 2020, 35, 1 .

AMA Style

Daniel G. Beach, Cheryl Rafuse, Jeremy E. Melanson, Pearse McCarron. Rapid quantitative screening of cyanobacteria for production of anatoxins using direct analysis in real time high‐resolution mass spectrometry. Rapid Communications in Mass Spectrometry. 2020; 35 (1):1.

Chicago/Turabian Style

Daniel G. Beach; Cheryl Rafuse; Jeremy E. Melanson; Pearse McCarron. 2020. "Rapid quantitative screening of cyanobacteria for production of anatoxins using direct analysis in real time high‐resolution mass spectrometry." Rapid Communications in Mass Spectrometry 35, no. 1: 1.

Journal article
Published: 20 August 2020 in Toxins
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Dihydrodinophysistoxin-1 (dihydro-DTX1, (M-H)-m/z 819.5), described previously from a marine sponge but never identified as to its biological source or described in shellfish, was detected in multiple species of commercial shellfish collected from the central coast of the Gulf of Maine, USA in 2016 and in 2018 during blooms of the dinoflagellate Dinophysis norvegica. Toxin screening by protein phosphatase inhibition (PPIA) first detected the presence of diarrhetic shellfish poisoning-like bioactivity; however, confirmatory analysis using liquid chromatography-tandem mass spectrometry (LC-MS/MS) failed to detect okadaic acid (OA, (M-H)-m/z 803.5), dinophysistoxin-1 (DTX1, (M-H)-m/z 817.5), or dinophysistoxin-2 (DTX2, (M-H)-m/z 803.5) in samples collected during the bloom. Bioactivity-guided fractionation followed by liquid chromatography-high resolution mass spectrometry (LC-HRMS) tentatively identified dihydro-DTX1 in the PPIA active fraction. LC-MS/MS measurements showed an absence of OA, DTX1, and DTX2, but confirmed the presence of dihydro-DTX1 in shellfish during blooms of D. norvegica in both years, with results correlating well with PPIA testing. Two laboratory cultures of D. norvegica isolated from the 2018 bloom were found to produce dihydro-DTX1 as the sole DSP toxin, confirming the source of this compound in shellfish. Estimated concentrations of dihydro-DTX1 were >0.16 ppm in multiple shellfish species (max. 1.1 ppm) during the blooms in 2016 and 2018. Assuming an equivalent potency and molar response to DTX1, the authority initiated precautionary shellfish harvesting closures in both years. To date, no illnesses have been associated with the presence of dihydro-DTX1 in shellfish in the Gulf of Maine region and studies are underway to determine the potency of this new toxin relative to the currently regulated DSP toxins in order to develop appropriate management guidance.

ACS Style

Jonathan R. Deeds; Whitney L. Stutts; Mary Dawn Celiz; Jill MacLeod; Amy E. Hamilton; Bryant J. Lewis; David W. Miller; Kohl Kanwit; Juliette L. Smith; David M. Kulis; Pearse McCarron; Carlton D. Rauschenberg; Craig A. Burnell; Stephen D. Archer; Jerry Borchert; Shelley K. Lankford. Dihydrodinophysistoxin-1 Produced by Dinophysis norvegica in the Gulf of Maine, USA and Its Accumulation in Shellfish. Toxins 2020, 12, 533 .

AMA Style

Jonathan R. Deeds, Whitney L. Stutts, Mary Dawn Celiz, Jill MacLeod, Amy E. Hamilton, Bryant J. Lewis, David W. Miller, Kohl Kanwit, Juliette L. Smith, David M. Kulis, Pearse McCarron, Carlton D. Rauschenberg, Craig A. Burnell, Stephen D. Archer, Jerry Borchert, Shelley K. Lankford. Dihydrodinophysistoxin-1 Produced by Dinophysis norvegica in the Gulf of Maine, USA and Its Accumulation in Shellfish. Toxins. 2020; 12 (9):533.

Chicago/Turabian Style

Jonathan R. Deeds; Whitney L. Stutts; Mary Dawn Celiz; Jill MacLeod; Amy E. Hamilton; Bryant J. Lewis; David W. Miller; Kohl Kanwit; Juliette L. Smith; David M. Kulis; Pearse McCarron; Carlton D. Rauschenberg; Craig A. Burnell; Stephen D. Archer; Jerry Borchert; Shelley K. Lankford. 2020. "Dihydrodinophysistoxin-1 Produced by Dinophysis norvegica in the Gulf of Maine, USA and Its Accumulation in Shellfish." Toxins 12, no. 9: 533.

Journal article
Published: 16 June 2020 in Toxins
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Paralytic shellfish toxins (PSTs) are a complex class of analogs of the potent neurotoxin saxitoxin (STX). Since calibration standards are not available for many PSTs, including C-11 hydroxyl analogs called M-toxins, accurate quantitation by liquid chromatography–mass spectrometry (LC-MS) can be challenging. In the absence of standards, PSTs are often semiquantitated using standards of a different analog (e.g., STX), an approach with a high degree of uncertainty due to the highly variable sensitivity between analytes in electrospray ionization. Here, relative molar response factors (RMRs) were investigated for a broad range of PSTs using common LC-MS approaches in order to improve the quantitation of PSTs for which standards are unavailable. First, several M-toxins (M1-M6, M9 and dcM6) were semipurified from shellfish using preparative gel filtration chromatography and quantitated using LC-charged aerosol detection (LC-CAD). The RMRs of PST certified reference materials (CRMs) and M-toxins were then determined using selective reaction monitoring LC-MS/MS and full scan LC-high-resolution MS (LC-HRMS) methods in positive and negative electrospray ionization. In general, RMRs for PSTs with similar chemical structures were comparable, but varied significantly between subclasses, with M-toxins showing the lowest sensitivity. For example, STX showed a greater than 50-fold higher RMR than M4 and M6 by LC-HRMS. The MS instrument, scan mode and polarity also had significant impacts on RMRs and should be carefully considered when semiquantitating PSTs by LC-MS. As a demonstration of their utility, the RMRs determined were applied to the semiquantitation of PSTs in contaminated mussels, showing good agreement with results from calibration with CRMs.

ACS Style

Jiangbing Qiu; Elliott J. Wright; Krista Thomas; Aifeng Li; Pearse McCarron; Daniel G. Beach. Semiquantitation of Paralytic Shellfish Toxins by Hydrophobic Interaction Liquid Chromatography-Mass Spectrometry Using Relative Molar Response Factors. Toxins 2020, 12, 1 .

AMA Style

Jiangbing Qiu, Elliott J. Wright, Krista Thomas, Aifeng Li, Pearse McCarron, Daniel G. Beach. Semiquantitation of Paralytic Shellfish Toxins by Hydrophobic Interaction Liquid Chromatography-Mass Spectrometry Using Relative Molar Response Factors. Toxins. 2020; 12 (6):1.

Chicago/Turabian Style

Jiangbing Qiu; Elliott J. Wright; Krista Thomas; Aifeng Li; Pearse McCarron; Daniel G. Beach. 2020. "Semiquantitation of Paralytic Shellfish Toxins by Hydrophobic Interaction Liquid Chromatography-Mass Spectrometry Using Relative Molar Response Factors." Toxins 12, no. 6: 1.

Preprint content
Published: 16 April 2020
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Cyanobacteria form harmful mass blooms in freshwater and marine environments around the world. A range of secondary metabolites has been identified from cultures of cyanobacteria and biomass collected from cyanobacterial bloom events. A comprehensive database is necessary to correctly identify cyanobacterial metabolites and advance research on their abundance, persistence and toxicity in natural environments. We consolidated open access databases and manually curated missing information from the literature published between 1970 and March 2020. The result is the database CyanoMetDB, which includes more than 2000 entries based on more than 750 literature references. This effort has more than doubled the total number of entries with complete literature metadata and structural composition (SMILES codes) compared to publicly available databases to this date. Over the past decade, more than one hundred additional secondary metabolites have been identified yearly. We organized all entries into structural classes and conducted substructure searches of the provided SMILES codes. This approach demonstrated, for example, that 65% of the compounds carry at least one peptide bond, 57% are cyclic compounds, and 30% carry at least one halogen atom. Structural searches by SMILES code can be further specified to identify structural motifs that are relevant for analytical approaches, research on biosynthetic pathways, bioactivity-guided analysis, or to facilitate predictive science and modeling efforts on cyanobacterial metabolites. This database facilitates rapid identification of cyanobacterial metabolites from toxic blooms, research on the biosynthesis of cyanobacterial natural products, and the identification of novel natural products from cyanobacteria.

ACS Style

Martin R. Jones; Ernani Pinto; Mariana A. Torres; Fabiane Doerr; Hanna Mazur-Marzec; Karolina Szubert; Luciana Tartaglione; Carmela Dell’Aversano; Christopher O. Miles; Daniel G. Beach; Pearse McCarron; Kaarina Sivonen; David P. Fewer; Jouni Jokela; Elisabeth M.-L. Janssen. Comprehensive database of secondary metabolites from cyanobacteria. 2020, 1 .

AMA Style

Martin R. Jones, Ernani Pinto, Mariana A. Torres, Fabiane Doerr, Hanna Mazur-Marzec, Karolina Szubert, Luciana Tartaglione, Carmela Dell’Aversano, Christopher O. Miles, Daniel G. Beach, Pearse McCarron, Kaarina Sivonen, David P. Fewer, Jouni Jokela, Elisabeth M.-L. Janssen. Comprehensive database of secondary metabolites from cyanobacteria. . 2020; ():1.

Chicago/Turabian Style

Martin R. Jones; Ernani Pinto; Mariana A. Torres; Fabiane Doerr; Hanna Mazur-Marzec; Karolina Szubert; Luciana Tartaglione; Carmela Dell’Aversano; Christopher O. Miles; Daniel G. Beach; Pearse McCarron; Kaarina Sivonen; David P. Fewer; Jouni Jokela; Elisabeth M.-L. Janssen. 2020. "Comprehensive database of secondary metabolites from cyanobacteria." , no. : 1.

Journal article
Published: 20 February 2020 in Harmful Algae
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Marine shellfish exposed to the microalgae Karenia selliformis can accumulate gymnodimines (GYM). Shellfish samples collected from Beihai City in Guangxi Autonomous Region, and Ningde City in Fujian Province, in the South China Sea, as well as mussels Mytilus galloprovincialis fed on K. selliformis under laboratory conditions were analyzed. Gymnodimines and various fatty acid ester metabolites were detected in the clam Antigona lamellaris and pen shell Atrina pectinata, while no esters were found in the oyster Crassostrea sp. and the gastropod Batillaria zonalis despite positive detection of free GYM in both species. When present, the predominant acyl esters observed were 18:0-GYM-A and 20:1-GYM-A. Under laboratory conditions GYM-A was accumulated and metabolized to fatty acid esters in mussels exposed to K. selliformis, with 16:0-GYM-A and 20:1-GYM-A as the major variants. A novel compound with the same accurate mass as GYM-A and its 16:0 fatty acid ester were observed in the experimental mussels but was not present in the microalgal strain to which mussels were exposed. No significant differences of reactive oxygen species (ROS) levels and antioxidant enzymes were found between mussels fed on K. selliformis or GYM-free microalgae Isochrysis galbana. This suggests the accumulation of GYM and its metabolites does not significantly impact the physiological status of mussels. While it is currently not proven that GYM affects human health, risk assessments should consider the presence of GYM esters in naturally contaminated shellfish as part of exposure analysis.

ACS Style

Ying Ji; Yijia Che; Elliott J. Wright; Pearse McCarron; Philipp Hess; Aifeng Li. Fatty acid ester metabolites of gymnodimine in shellfish collected from China and in mussels (Mytilus galloprovincialis) exposed to Karenia selliformis. Harmful Algae 2020, 92, 101774 .

AMA Style

Ying Ji, Yijia Che, Elliott J. Wright, Pearse McCarron, Philipp Hess, Aifeng Li. Fatty acid ester metabolites of gymnodimine in shellfish collected from China and in mussels (Mytilus galloprovincialis) exposed to Karenia selliformis. Harmful Algae. 2020; 92 ():101774.

Chicago/Turabian Style

Ying Ji; Yijia Che; Elliott J. Wright; Pearse McCarron; Philipp Hess; Aifeng Li. 2020. "Fatty acid ester metabolites of gymnodimine in shellfish collected from China and in mussels (Mytilus galloprovincialis) exposed to Karenia selliformis." Harmful Algae 92, no. : 101774.

Journal article
Published: 23 January 2020 in Toxins
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[D-Leu1]MC-LY (1) ([M + H]+ m/z 1044.5673, Δ 2.0 ppm), a new microcystin, was isolated from Microcystis aeruginosa strain CPCC-464. The compound was characterized by 1H and 13C NMR spectroscopy, liquid chromatography–high resolution tandem mass spectrometry (LC–HRMS/MS) and UV spectroscopy. A calibration reference material was produced after quantitation by 1H NMR spectroscopy and LC with chemiluminescence nitrogen detection. The potency of 1 in a protein phosphatase 2A inhibition assay was essentially the same as for MC-LR (2). Related microcystins, [D-Leu1]MC-LR (3) ([M + H]+ m/z 1037.6041, Δ 1.0 ppm), [D-Leu1]MC-M(O)R (6) ([M + H]+ m/z 1071.5565, Δ 2.0 ppm) and [D-Leu1]MC-MR (7) ([M + H]+ m/z 1055.5617, Δ 2.2 ppm), were also identified in culture extracts, along with traces of [D-Leu1]MC-M(O2)R (8) ([M + H]+ m/z 1087.5510, Δ 1.6 ppm), by a combination of chemical derivatization and LC–HRMS/MS experiments. The relative abundances of 1, 3, 6, 7 and 8 in a freshly extracted culture in the positive ionization mode LC–HRMS were ca. 84, 100, 3.0, 11 and 0.05, respectively. These and other results indicate that [D-Leu1]-containing MCs may be more common in cyanobacterial blooms than is generally appreciated but are easily overlooked with standard targeted LC–MS/MS screening methods.

ACS Style

Patricia Leblanc; Nadine Merkley; Krista Thomas; Nancy I. Lewis; Khalida Békri; Susan LeBlanc Renaud; Frances R. Pick; Pearse McCarron; Christopher O. Miles; Michael A. Quilliam. Isolation and Characterization of [D-Leu1]microcystin-LY from Microcystis aeruginosa CPCC-464. Toxins 2020, 12, 77 .

AMA Style

Patricia Leblanc, Nadine Merkley, Krista Thomas, Nancy I. Lewis, Khalida Békri, Susan LeBlanc Renaud, Frances R. Pick, Pearse McCarron, Christopher O. Miles, Michael A. Quilliam. Isolation and Characterization of [D-Leu1]microcystin-LY from Microcystis aeruginosa CPCC-464. Toxins. 2020; 12 (2):77.

Chicago/Turabian Style

Patricia Leblanc; Nadine Merkley; Krista Thomas; Nancy I. Lewis; Khalida Békri; Susan LeBlanc Renaud; Frances R. Pick; Pearse McCarron; Christopher O. Miles; Michael A. Quilliam. 2020. "Isolation and Characterization of [D-Leu1]microcystin-LY from Microcystis aeruginosa CPCC-464." Toxins 12, no. 2: 77.

Review article
Published: 08 July 2019 in Journal of Natural Products
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Liquid chromatography–high-resolution mass spectrometry (LC-HRMS) analysis of a Namibian strain of Gonyaulax spinifera showed the presence of a number of yessotoxins (YTXs). Principal among these were YTX (1), homoYTX (2), and a tentative hydroxylated analogue that did not correspond to any previously confirmed YTX structures. Culturing the G. spinifera strain afforded sufficient biomass for purification of the new analogue through a series of solvent partitioning and chromatographic steps, yielding ∼0.9 mg as a solid. NMR spectroscopy, ion-trap mass spectrometry, and HRMS identified the new analogue as 24-hydroxyYTX (7). Purified 24-hydroxyYTX was quantitated by NMR, and its relative toxicity evaluated using two embryonic zebrafish toxicity assays. 24-HydroxyYTX demonstrated reduced toxicity compared to YTX.

ACS Style

Isabelle Rajotte; Cheryl Rafuse; Elliott J. Wright; John C. Achenbach; Lee D. Ellis; Pearse McCarron. Structure Elucidation and Relative Toxicity of (24R)-24-Hydroxyyessotoxin from a Namibian Isolate of Gonyaulax spinifera. Journal of Natural Products 2019, 82, 1945 -1952.

AMA Style

Isabelle Rajotte, Cheryl Rafuse, Elliott J. Wright, John C. Achenbach, Lee D. Ellis, Pearse McCarron. Structure Elucidation and Relative Toxicity of (24R)-24-Hydroxyyessotoxin from a Namibian Isolate of Gonyaulax spinifera. Journal of Natural Products. 2019; 82 (7):1945-1952.

Chicago/Turabian Style

Isabelle Rajotte; Cheryl Rafuse; Elliott J. Wright; John C. Achenbach; Lee D. Ellis; Pearse McCarron. 2019. "Structure Elucidation and Relative Toxicity of (24R)-24-Hydroxyyessotoxin from a Namibian Isolate of Gonyaulax spinifera." Journal of Natural Products 82, no. 7: 1945-1952.

Journal article
Published: 01 May 2019 in Harmful Algae
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The Benguela Current in the Atlantic is one of the four major upwelling systems on the Eastern boundary of the world ocean. Thus the coastal regions off Namibia are prone to high primary productivity that can lead to Harmful Algae Blooms as this nutrient rich water reaches the euphotic zone. Yessotoxins (YTXs) produced by G. spinifera were detected in Namibian phytoplankton field samples in 2011. Isolation of G. spinifera cultures from this location in 2012 enabled molecular genetics work and further liquid chromatography-mass spectrometry assessment of toxin profiles. The molecular work grouped the Benguela G. spinifera with other toxic G. spinifera strains originating from Italy and New Zealand. The main YTX analogs present in the Benguela G. spinifera are homo-YTX, YTX and a hydroxylated analogue. This work adds important knowledge on the occurrence of Harmful Algae Blooms in this region and is of relevance for safety.

ACS Style

Chibo Chikwililwa; Pearse McCarron; Joanna J. Waniek; Detlef E. Schulz-Bull. Phylogenetic analysis and yessotoxin profiles of Gonyaulax spinifera cultures from the Benguela Current upwelling system. Harmful Algae 2019, 85, 101626 .

AMA Style

Chibo Chikwililwa, Pearse McCarron, Joanna J. Waniek, Detlef E. Schulz-Bull. Phylogenetic analysis and yessotoxin profiles of Gonyaulax spinifera cultures from the Benguela Current upwelling system. Harmful Algae. 2019; 85 ():101626.

Chicago/Turabian Style

Chibo Chikwililwa; Pearse McCarron; Joanna J. Waniek; Detlef E. Schulz-Bull. 2019. "Phylogenetic analysis and yessotoxin profiles of Gonyaulax spinifera cultures from the Benguela Current upwelling system." Harmful Algae 85, no. : 101626.

International bodies
Published: 12 October 2018 in Accreditation and Quality Assurance
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ACS Style

Håkan Emteborg; Doris Florian; Steven Choquette; Stephen L. R. Ellison; Maria Fernandes-Whaley; Lindsey Mackay; Pearse McCarron; Ulrich Panne; Sylvia G. Sander; Sook-Kyung Kim; Andrea Held; Thomas Linsinger; Stefanie Trapmann. Cooperation in publicly funded reference material production. Accreditation and Quality Assurance 2018, 23, 371 -377.

AMA Style

Håkan Emteborg, Doris Florian, Steven Choquette, Stephen L. R. Ellison, Maria Fernandes-Whaley, Lindsey Mackay, Pearse McCarron, Ulrich Panne, Sylvia G. Sander, Sook-Kyung Kim, Andrea Held, Thomas Linsinger, Stefanie Trapmann. Cooperation in publicly funded reference material production. Accreditation and Quality Assurance. 2018; 23 (6):371-377.

Chicago/Turabian Style

Håkan Emteborg; Doris Florian; Steven Choquette; Stephen L. R. Ellison; Maria Fernandes-Whaley; Lindsey Mackay; Pearse McCarron; Ulrich Panne; Sylvia G. Sander; Sook-Kyung Kim; Andrea Held; Thomas Linsinger; Stefanie Trapmann. 2018. "Cooperation in publicly funded reference material production." Accreditation and Quality Assurance 23, no. 6: 371-377.

Journal article
Published: 06 July 2018 in Harmful Algae
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The dinoflagellate genus Alexandrium Halim has frequently been associated with harmful algal blooms. Although a number of species from this genus are known to produce paralytic shellfish toxins (PST) and/or cyclic imines (CI), studies on comprehensive toxin profiling using techniques capable of detecting the full range of PST and CI analogues are limited. Isolates of Alexandrium spp. from Atlantic Canada were analyzed by targeted and untargeted liquid chromatography-tandem mass spectrometry (LC–MS). Results showed a number of distinct profiles and wide ranging cell quotas of PST and spirolides (SPX) in both A. catenella (Whedon & Kofoid) Balech and A. ostenfedii (Paulsen) Balech & Tangen. The concentration of PST in A. catenella ranged from 0.0029 to 54 fmol cell−1 with the major components being C2 and GTX4. In addition, putative PST metabolites were confirmed for the first time in A. catenella by high resolution MS/MS. By comparison, A. ostenfeldii isolates showed much lower concentrations of PST (

ACS Style

Jiangbing Qiu; Cheryl Rafuse; Nancy I. Lewis; Aifeng Li; Fanping Meng; Daniel G. Beach; Pearse McCarron. Screening of cyclic imine and paralytic shellfish toxins in isolates of the genus Alexandrium (Dinophyceae) from Atlantic Canada. Harmful Algae 2018, 77, 108 -118.

AMA Style

Jiangbing Qiu, Cheryl Rafuse, Nancy I. Lewis, Aifeng Li, Fanping Meng, Daniel G. Beach, Pearse McCarron. Screening of cyclic imine and paralytic shellfish toxins in isolates of the genus Alexandrium (Dinophyceae) from Atlantic Canada. Harmful Algae. 2018; 77 ():108-118.

Chicago/Turabian Style

Jiangbing Qiu; Cheryl Rafuse; Nancy I. Lewis; Aifeng Li; Fanping Meng; Daniel G. Beach; Pearse McCarron. 2018. "Screening of cyclic imine and paralytic shellfish toxins in isolates of the genus Alexandrium (Dinophyceae) from Atlantic Canada." Harmful Algae 77, no. : 108-118.

Book chapter
Published: 01 June 2018 in Harmful Algal Blooms
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The ability to mitigate the adverse impacts of harmful algal blooms (HAB) on humans, wildlife, fisheries, and ecosystems, as well as to identify the environmental factors driving HAB population growth and toxicity, is based largely on early detection of causative organisms and their toxins. This chapter explores a wide range of organism and toxin detection methods and technologies. It describes the fundamental principles of operation/conduct. It outlines the prospects for future advances in bloom and toxin detection/surveillance capabilities. Molecular methods used to detect organisms are potentially faster and more accurate than light microscopy (LM) methods. Monoclonal antibodies (MAbs) and polyclonal antibodies have been used to detect cultured and field‐collected cells of a wide variety of harmful algae. Immunoassays are based on antibodies recognizing and binding to one or more epitopes or antigenic determinants on a toxin molecule. The Enzyme‐Linked Immunosorbent Assay, ELISA has been the format of choice for most commercial algal toxin detection kits.

ACS Style

Gregory J. Doucette; Linda K. Medlin; Pearse McCarron; Philipp Hess. Detection and Surveillance of Harmful Algal Bloom Species and Toxins. Harmful Algal Blooms 2018, 39 -114.

AMA Style

Gregory J. Doucette, Linda K. Medlin, Pearse McCarron, Philipp Hess. Detection and Surveillance of Harmful Algal Bloom Species and Toxins. Harmful Algal Blooms. 2018; ():39-114.

Chicago/Turabian Style

Gregory J. Doucette; Linda K. Medlin; Pearse McCarron; Philipp Hess. 2018. "Detection and Surveillance of Harmful Algal Bloom Species and Toxins." Harmful Algal Blooms , no. : 39-114.

Paper in forefront
Published: 16 May 2018 in Analytical and Bioanalytical Chemistry
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Polar marine toxins are more challenging to analyze by mass spectrometry-based methods than lipophilic marine toxins, which are now routinely measured in shellfish by multiclass reversed-phase liquid chromatography–tandem mass spectrometry (MS/MS) methods. Capillary electrophoresis (CE)–MS/MS is a technique that is well suited for the analysis of polar marine toxins, and has the potential of providing very high resolution separation. Here, we present a CE–MS/MS method developed, with use of a custom-built interface, for the sensitive multiclass analysis of paralytic shellfish toxins, tetrodotoxins, and domoic acid in seafood. A novel, highly acidic background electrolyte (5 M formic acid) was designed to maximize protonation of analytes and to allow a high degree of sample stacking to improve the limits of detection. The method was applied to a wide range of regulated and less common toxin analogues, and exhibited a high degree of selectivity between toxin isomers and matrix interference. The limits of detection in mussel tissue were 0.0052 mg/kg for tetrodotoxins, 0.160 mg/kg for domoic acid, and between 0.0018 and 0.120 mg/kg for paralytic shellfish toxins, all of which showed good linearity. Minimal ionization suppression was observed when the response from neat and mussel-matrix-matched standards was corrected with multiple internal standards. Analysis of shellfish matrix reference materials and spiked samples demonstrated good accuracy and precision. Finally, the method was transferred to a commercial CE–MS/MS system to demonstrate its widespread applicability for use in both R & D and routine regulatory settings. The approach of using a highly acidic background electrolyte is of broad interest, and can be considered generally applicable to simultaneous analysis of other classes of small, polar molecules with differing pKa values.

ACS Style

Daniel G. Beach; Elliott S. Kerrin; Krista Thomas; Michael Quilliam; Pearse McCarron. Capillary electrophoresis–tandem mass spectrometry for multiclass analysis of polar marine toxins. Analytical and Bioanalytical Chemistry 2018, 410, 5405 -5420.

AMA Style

Daniel G. Beach, Elliott S. Kerrin, Krista Thomas, Michael Quilliam, Pearse McCarron. Capillary electrophoresis–tandem mass spectrometry for multiclass analysis of polar marine toxins. Analytical and Bioanalytical Chemistry. 2018; 410 (22):5405-5420.

Chicago/Turabian Style

Daniel G. Beach; Elliott S. Kerrin; Krista Thomas; Michael Quilliam; Pearse McCarron. 2018. "Capillary electrophoresis–tandem mass spectrometry for multiclass analysis of polar marine toxins." Analytical and Bioanalytical Chemistry 410, no. 22: 5405-5420.

Journal article
Published: 01 May 2018 in Harmful Algae
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Benthic dinoflagellates of the toxigenic genus Coolia Meunier (Dinophyceae) are known to have a global distribution in both tropical and temperate waters. The type species, C. monotis, has been reported from the Mediterranean Sea, the NE Atlantic and from Rhode Island, USA in the NW Atlantic, whereas other species in the genus have been reported from tropical locations. Coolia cells were observed in algal drift samples collected at seven sites in Nova Scotia, Canada. Clonal isolates were established from four of these locations and identified with light and scanning electron microscopy, then confirmed with genetic sequencing to be C. monotis. This is the first record of this species in Nova Scotia. The isolates were established and incubated at 18 °C under a 14:10 L:D photoperiod with an approximate photon flux density of 50-60 μmol m s. Growth experiments using an isolate from Johnston Harbour (CMJH) were carried out at temperatures ranging from 5 to 30 °C under the same photoperiod with an approximate photon flux density of 45-50 μmol m s. Cells tolerated temperatures from 5 to 25 °C with optimum growth and mucilage aggregate production between 15 and 20 °C. Methanol extracts of this isolate examined by Liquid Chromatography-Mass Spectrometry (LC-MS) did not show the presence of the previously reported cooliatoxin. Toxic effects were assayed using two zebrafish bioassays, the Fish Embryo Toxicity (FET) assay and the General Behaviour and Toxicity (GBT) assay. The results of this study demonstrate a lack of toxicity in C. monotis from Nova Scotia, as has been reported for other genetically-confirmed isolates of this species. Conditions in which cell growth that could potentially degrade water quality and provide substrate and dispersal mechanisms for other harmful microorganisms via mucilage production are indicated.

ACS Style

Nancy I. Lewis; Jennifer L. Wolny; John Claude Achenbach; Lee Ellis; Joseph S. Pitula; Cheryl Rafuse; Detbra S. Rosales; Pearse McCarron. Identification, growth and toxicity assessment of Coolia Meunier (Dinophyceae) from Nova Scotia, Canada. Harmful Algae 2018, 75, 45 -56.

AMA Style

Nancy I. Lewis, Jennifer L. Wolny, John Claude Achenbach, Lee Ellis, Joseph S. Pitula, Cheryl Rafuse, Detbra S. Rosales, Pearse McCarron. Identification, growth and toxicity assessment of Coolia Meunier (Dinophyceae) from Nova Scotia, Canada. Harmful Algae. 2018; 75 ():45-56.

Chicago/Turabian Style

Nancy I. Lewis; Jennifer L. Wolny; John Claude Achenbach; Lee Ellis; Joseph S. Pitula; Cheryl Rafuse; Detbra S. Rosales; Pearse McCarron. 2018. "Identification, growth and toxicity assessment of Coolia Meunier (Dinophyceae) from Nova Scotia, Canada." Harmful Algae 75, no. : 45-56.

Journal article
Published: 01 March 2018 in Toxicon
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Azaspiracid (AZA) producing microalgae have been reported internationally and could potentially impact a variety of seafood. Scallops (Chlamys farreri) and mussels (Mytilus galloprovincialis) from China were fed with the AZA2 producer, Azadinium poporum, to study uptake, metabolism and oxidative stress in the shellfish. LC-MS/MS showed significant accumulation and differential metabolism of AZA2 in the scallops and mussels. In mussels AZA2 was metabolized to AZA19, with subsequent decarboxylation to AZA6. In scallops no AZA19 or AZA6 was observed, however, a novel AZA metabolite was formed with that is isobaric with AZA19 ([M+H]+, m/z 886), but elutes at a different retention time. In addition it was noted that the scallop metabolite was stable during heating, while AZA19 has been shown to decarboxylate. Concentrations of reactive oxygen species (ROS) and activities of antioxidant enzymes were monitored. ROS levels slightly increased in the meat of scallops and mussels due to starvation in the acclimation and depuration periods, but reduced in the feeding periods with non-toxic Isochrysis galbana or toxic A. poporum. No obvious variations were found for the activities of a range of antioxidant enzymes. These results provide new insights on the potential for accumulation and metabolism of AZAs in bivalve species relevant to this area of China, which is of importance considering the recent finding of AZA producing algae in the region.

ACS Style

Ying Ji; Jiangbing Qiu; Tian Xie; Pearse McCarron; Aifeng Li. Accumulation and transformation of azaspiracids in scallops ( Chlamys farreri ) and mussels ( Mytilus galloprovincialis ) fed with Azadinium poporum, and response of antioxidant enzymes. Toxicon 2018, 143, 20 -28.

AMA Style

Ying Ji, Jiangbing Qiu, Tian Xie, Pearse McCarron, Aifeng Li. Accumulation and transformation of azaspiracids in scallops ( Chlamys farreri ) and mussels ( Mytilus galloprovincialis ) fed with Azadinium poporum, and response of antioxidant enzymes. Toxicon. 2018; 143 ():20-28.

Chicago/Turabian Style

Ying Ji; Jiangbing Qiu; Tian Xie; Pearse McCarron; Aifeng Li. 2018. "Accumulation and transformation of azaspiracids in scallops ( Chlamys farreri ) and mussels ( Mytilus galloprovincialis ) fed with Azadinium poporum, and response of antioxidant enzymes." Toxicon 143, no. : 20-28.

Article
Published: 15 January 2018 in Angewandte Chemie International Edition
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A convergent and stereoselective total synthesis of the previously assigned structure of azaspiracid-3 has been achieved via a late stage NHK coupling to form the C21‒C22 bond with the C20 configuration unambiguously established from L-(+)-tartaric acid. Post-coupling steps involved oxidation to an ynone, modified Stryker reduction of the alkyne, global deprotection, and oxidation of the primary alcohol to the carboxylic acid. The synthetic product matched naturally occurring azaspiracid-3 by mass spectrometry, but differed both chromatographically and spectroscopically.

ACS Style

Nathaniel T. Kenton; Daniel Adu-Ampratwum; Antony A. Okumu; Zhigao Zhang; Yong Chen; Son Nguyen; Jianyan Xu; Yue Ding; Pearse McCarron; Jane Kilcoyne; Frode Rise; Alistair L. Wilkins; Christopher O. Miles; Craig J. Forsyth. Total Synthesis of (6 R ,10 R ,13 R ,14 R ,16 R ,17 R ,19 S ,20 R ,21 R ,24 S , 25 S ,28 S ,30 S ,32 R ,33 R ,34 R ,36 S ,37 S ,39 R )‐Azaspiracid‐3 Reveals Non‐Identity with the Natural Product. Angewandte Chemie International Edition 2018, 57, 805 -809.

AMA Style

Nathaniel T. Kenton, Daniel Adu-Ampratwum, Antony A. Okumu, Zhigao Zhang, Yong Chen, Son Nguyen, Jianyan Xu, Yue Ding, Pearse McCarron, Jane Kilcoyne, Frode Rise, Alistair L. Wilkins, Christopher O. Miles, Craig J. Forsyth. Total Synthesis of (6 R ,10 R ,13 R ,14 R ,16 R ,17 R ,19 S ,20 R ,21 R ,24 S , 25 S ,28 S ,30 S ,32 R ,33 R ,34 R ,36 S ,37 S ,39 R )‐Azaspiracid‐3 Reveals Non‐Identity with the Natural Product. Angewandte Chemie International Edition. 2018; 57 (3):805-809.

Chicago/Turabian Style

Nathaniel T. Kenton; Daniel Adu-Ampratwum; Antony A. Okumu; Zhigao Zhang; Yong Chen; Son Nguyen; Jianyan Xu; Yue Ding; Pearse McCarron; Jane Kilcoyne; Frode Rise; Alistair L. Wilkins; Christopher O. Miles; Craig J. Forsyth. 2018. "Total Synthesis of (6 R ,10 R ,13 R ,14 R ,16 R ,17 R ,19 S ,20 R ,21 R ,24 S , 25 S ,28 S ,30 S ,32 R ,33 R ,34 R ,36 S ,37 S ,39 R )‐Azaspiracid‐3 Reveals Non‐Identity with the Natural Product." Angewandte Chemie International Edition 57, no. 3: 805-809.

Article
Published: 15 December 2017 in Angewandte Chemie
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The previously accepted structure of the marine toxin azaspiracid-3 is revised based upon an original convergent and stereoselective total synthesis of the natural product. The development of a structural revision hypothesis, its testing, and corroboration are reported. Synthetic (6R,10R,13R,14R,16R,17R, 19S,20S,21R,24S,25S,28S,30S,32R,33R,34R,36S,37S,39R)-azaspiracid-3 chromatographically and spectroscopically matched naturally occurring azaspiracid-3, whereas the previously assigned (20R)-epimer did not.

ACS Style

Nathaniel T. Kenton; Daniel Adu-Ampratwum; Antony A. Okumu; Pearse McCarron; Jane Kilcoyne; Frode Rise; Alistair L. Wilkins; Christopher O. Miles; Craig J. Forsyth. Stereochemical Definition of the Natural Product (6 R ,10 R ,13 R , 14 R ,16 R ,17 R ,19 S ,20 S ,21 R ,24 S ,25 S ,28 S ,30 S ,32 R ,33 R ,34 R ,36 S ,37 S ,39 R )‐Azaspiracid‐3 by Total Synthesis and Comparative Analyses. Angewandte Chemie 2017, 130, 818 -821.

AMA Style

Nathaniel T. Kenton, Daniel Adu-Ampratwum, Antony A. Okumu, Pearse McCarron, Jane Kilcoyne, Frode Rise, Alistair L. Wilkins, Christopher O. Miles, Craig J. Forsyth. Stereochemical Definition of the Natural Product (6 R ,10 R ,13 R , 14 R ,16 R ,17 R ,19 S ,20 S ,21 R ,24 S ,25 S ,28 S ,30 S ,32 R ,33 R ,34 R ,36 S ,37 S ,39 R )‐Azaspiracid‐3 by Total Synthesis and Comparative Analyses. Angewandte Chemie. 2017; 130 (3):818-821.

Chicago/Turabian Style

Nathaniel T. Kenton; Daniel Adu-Ampratwum; Antony A. Okumu; Pearse McCarron; Jane Kilcoyne; Frode Rise; Alistair L. Wilkins; Christopher O. Miles; Craig J. Forsyth. 2017. "Stereochemical Definition of the Natural Product (6 R ,10 R ,13 R , 14 R ,16 R ,17 R ,19 S ,20 S ,21 R ,24 S ,25 S ,28 S ,30 S ,32 R ,33 R ,34 R ,36 S ,37 S ,39 R )‐Azaspiracid‐3 by Total Synthesis and Comparative Analyses." Angewandte Chemie 130, no. 3: 818-821.

Communication
Published: 28 November 2017 in Angewandte Chemie International Edition
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The previously accepted structure of the marine toxin azaspiracid‐3 is revised based upon an original convergent and stereoselective total synthesis of the natural product. The development of a structural revision hypothesis, its testing, and corroboration are reported. Synthetic (6R,10R,13R,14R,16R,17R,19S,20S,21R,24S,25S,28S,30S,32R, 33R,34R,36S,37S,39R)‐azaspiracid‐3 chromatographically and spectroscopically matched naturally occurring azaspiracid‐3, whereas the previously assigned 20R epimer did not.

ACS Style

Nathaniel T. Kenton; Daniel Adu-Ampratwum; Antony A. Okumu; Pearse McCarron; Jane Kilcoyne; Dr. Frode Rise; Dr. Alistair L. Wilkins; Christopher O. Miles; Dr. Craig J. Forsyth. Stereochemical Definition of the Natural Product (6 R ,10 R ,13 R , 14 R ,16 R ,17 R ,19 S ,20 S ,21 R ,24 S ,25 S ,28 S ,30 S ,32 R ,33 R ,34 R ,36 S ,37 S ,39 R )‐Azaspiracid‐3 by Total Synthesis and Comparative Analyses. Angewandte Chemie International Edition 2017, 57, 810 -813.

AMA Style

Nathaniel T. Kenton, Daniel Adu-Ampratwum, Antony A. Okumu, Pearse McCarron, Jane Kilcoyne, Dr. Frode Rise, Dr. Alistair L. Wilkins, Christopher O. Miles, Dr. Craig J. Forsyth. Stereochemical Definition of the Natural Product (6 R ,10 R ,13 R , 14 R ,16 R ,17 R ,19 S ,20 S ,21 R ,24 S ,25 S ,28 S ,30 S ,32 R ,33 R ,34 R ,36 S ,37 S ,39 R )‐Azaspiracid‐3 by Total Synthesis and Comparative Analyses. Angewandte Chemie International Edition. 2017; 57 (3):810-813.

Chicago/Turabian Style

Nathaniel T. Kenton; Daniel Adu-Ampratwum; Antony A. Okumu; Pearse McCarron; Jane Kilcoyne; Dr. Frode Rise; Dr. Alistair L. Wilkins; Christopher O. Miles; Dr. Craig J. Forsyth. 2017. "Stereochemical Definition of the Natural Product (6 R ,10 R ,13 R , 14 R ,16 R ,17 R ,19 S ,20 S ,21 R ,24 S ,25 S ,28 S ,30 S ,32 R ,33 R ,34 R ,36 S ,37 S ,39 R )‐Azaspiracid‐3 by Total Synthesis and Comparative Analyses." Angewandte Chemie International Edition 57, no. 3: 810-813.