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Timothy F Jamison - One of the best experts on this subject based on the ideXlab platform.
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a dioxane template for highly selective epoxy alcohol cyclizations
2013Co-Authors: James J Mousseau, Christopher J Morten, Timothy F JamisonAbstract:Ladder polyether natural products are a class of natural products denoted by their high functional group density and large number of well-defined stereocenters. They comprise the toxic component of harmful algal blooms (HABs), having significant negative economic and environmental ramifications. However, their mode of action, namely blocking various cellular ion channels, also denotes their promise as potential anticancer agents. Understanding their potential mode of biosynthesis will not only help with developing ways to limit the damage of HABs, but would also facilitate the synthesis of a range of analogues with interesting biological activity. 1,3-Dioxan-5-ol substrates display remarkable ‘enhanced template effects’ in water-promoted epoxide cyclization processes en route to the synthesis of these ladder polyether natural products. In many cases they provide near complete endo to exo selectivity in the cyclization of epoxy alcohols, thereby strongly favouring the formation of tetrahydropyran (THP) over tetrahydrofuran (THF) rings. The effects of various Bronsted and Lewis acidic and basic conditions are explored to demonstrate the superior selectivity of the template over the previously reported THP-based epoxy alcohols. In addition, the consideration of other synthetic routes are also considered with the goal of gaining rapid access to a plethora of potential starting materials applicable towards the synthesis of ladder Polyethers. Finally, cascade sequences with polyepoxides are investigated, further demonstrating the versatility of this new reaction template.
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synthesis of marine polycyclic Polyethers via endo selective epoxide opening cascades
2010Co-Authors: Ivan Vilotijevic, Timothy F JamisonAbstract:The proposed biosynthetic pathways to ladder Polyethers of polyketide origin and oxasqualenoids of terpenoid origin share a dramatic epoxide-opening cascade as a key step. Polycyclic structures generated in these biosynthetic pathways display biological effects ranging from potentially therapeutic properties to extreme lethality. Much of the structural complexity of ladder polyether and oxasqualenoid natural products can be traced to these hypothesized cascades. In this review we summarize how such epoxide-opening cascade reactions have been used in the synthesis of ladder Polyethers and oxasqualenoid natural products.
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the development of endo selective epoxide opening cascades in water
2009Co-Authors: Christopher J Morten, Jeffery A Byers, Aaron R Van Dyke, Ivan Vilotijevic, Timothy F JamisonAbstract:This tutorial review traces the development of endo-regioselective epoxide-opening reactions in water. Templated, water-promoted epoxide-opening cyclization reactions can offer rapid access to subunits of the ladder Polyethers, a fascinating and complex family of natural products. This review may be of interest to those curious about the ladder Polyethers and their hypothesized biogenesis, about organic reactions in water, and about the development and application of cascade reactions in organic synthesis.
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epoxide opening cascades in the synthesis of polycyclic polyether natural products
2009Co-Authors: Ivan Vilotijevic, Timothy F JamisonAbstract:The group of polycyclic polyether natural products is of special interest due to the fascinating structure and biological effects displayed by its members. The latter includes potentially therapeutic antibiotic, antifungal, and anticancer properties, as well as extreme lethality. The polycyclic structural features of this family can, in some cases, be traced to their biosynthetic origin, but in others that are less well understood, only to proposed biosynthetic pathways that feature dramatic, yet speculative, epoxide–opening cascades. In this review we summarize how such epoxide–opening cascade reactions have been used in the synthesis of polycyclic Polyethers and related natural products.
Masayoshi Watanabe - One of the best experts on this subject based on the ideXlab platform.
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Structural effects of Polyethers and ionic liquids in their binary mixtures on lower critical solution temperature liquid-liquid phase separation
2011Co-Authors: Koichi Kodama, Ryohei Tsuda, Kazuyuki Niitsuma, Takashi Tamura, Takeshi Ueki, Hisashi Kokubo, Masayoshi WatanabeAbstract:The solubility and phase behavior of five Polyethers (poly(ethylene oxide), poly(glycidyl methyl ether), poly(ethyl glycidyl ether), poly(ethoxyethyl glycidyl ether) and poly(propylene oxide)) in 14 different room-temperature ionic liquids (ILs) were studied by changing the structures of Polyethers and the cations and anions in the ILs. Certain combinations of a polyether and an IL binary mixture exhibited lower critical solution temperature (LCST) phase behavior. For ILs containing the same anions, the Polyethers were highly soluble in imidazolium- or pyridinium-based ILs, whereas they were insoluble in ammonium- or phosphonium-based ILs. An increase in length of the alkyl chain in the imidazolium cation and an increase in polarity of the Polyethers resulted in a higher LCST phase separation temperature, whereas substitution of the hydrogen atoms on the imidazolium ring by methyl groups resulted in a lower LCST phase separation temperature. The hydrogen bonding interaction between the oxygen atoms in the Polyethers and the aromatic hydrogen atoms on the cations in the ILs had an important role in the LCST phase behavior of the mixtures. Miscibility of the mixtures was also affected by the Lewis basicity of the anions in the ILs. The solubility and phase behavior of five Polyethers in 14 different room-temperature ionic liquids (ILs) were studied by changing the structures of Polyethers and the cations and anions in the ILs. Certain combinations of a polyether and an IL binary mixture exhibited lower critical solution temperature (LCST) phase behavior. The phase separation temperature (cloud point) was revealed to be sensitive to the aromaticity and alkyl chain length of the IL cations, the anionic Lewis basicities of the ILs and the polarity of the Polyethers. PEGE, poly(ethyl glycidyl ether).
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structural effects of Polyethers and ionic liquids in their binary mixtures on lower critical solution temperature liquid liquid phase separation
2011Co-Authors: Koichi Kodama, Ryohei Tsuda, Kazuyuki Niitsuma, Takashi Tamura, Takeshi Ueki, Hisashi Kokubo, Masayoshi WatanabeAbstract:The solubility and phase behavior of five Polyethers in 14 different room-temperature ionic liquids (ILs) were studied by changing the structures of Polyethers and the cations and anions in the ILs. Certain combinations of a polyether and an IL binary mixture exhibited lower critical solution temperature (LCST) phase behavior. The phase separation temperature (cloud point) was revealed to be sensitive to the aromaticity and alkyl chain length of the IL cations, the anionic Lewis basicities of the ILs and the polarity of the Polyethers. PEGE, poly(ethyl glycidyl ether).
Koichi Kodama - One of the best experts on this subject based on the ideXlab platform.
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Structural effects of Polyethers and ionic liquids in their binary mixtures on lower critical solution temperature liquid-liquid phase separation
2011Co-Authors: Koichi Kodama, Ryohei Tsuda, Kazuyuki Niitsuma, Takashi Tamura, Takeshi Ueki, Hisashi Kokubo, Masayoshi WatanabeAbstract:The solubility and phase behavior of five Polyethers (poly(ethylene oxide), poly(glycidyl methyl ether), poly(ethyl glycidyl ether), poly(ethoxyethyl glycidyl ether) and poly(propylene oxide)) in 14 different room-temperature ionic liquids (ILs) were studied by changing the structures of Polyethers and the cations and anions in the ILs. Certain combinations of a polyether and an IL binary mixture exhibited lower critical solution temperature (LCST) phase behavior. For ILs containing the same anions, the Polyethers were highly soluble in imidazolium- or pyridinium-based ILs, whereas they were insoluble in ammonium- or phosphonium-based ILs. An increase in length of the alkyl chain in the imidazolium cation and an increase in polarity of the Polyethers resulted in a higher LCST phase separation temperature, whereas substitution of the hydrogen atoms on the imidazolium ring by methyl groups resulted in a lower LCST phase separation temperature. The hydrogen bonding interaction between the oxygen atoms in the Polyethers and the aromatic hydrogen atoms on the cations in the ILs had an important role in the LCST phase behavior of the mixtures. Miscibility of the mixtures was also affected by the Lewis basicity of the anions in the ILs. The solubility and phase behavior of five Polyethers in 14 different room-temperature ionic liquids (ILs) were studied by changing the structures of Polyethers and the cations and anions in the ILs. Certain combinations of a polyether and an IL binary mixture exhibited lower critical solution temperature (LCST) phase behavior. The phase separation temperature (cloud point) was revealed to be sensitive to the aromaticity and alkyl chain length of the IL cations, the anionic Lewis basicities of the ILs and the polarity of the Polyethers. PEGE, poly(ethyl glycidyl ether).
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structural effects of Polyethers and ionic liquids in their binary mixtures on lower critical solution temperature liquid liquid phase separation
2011Co-Authors: Koichi Kodama, Ryohei Tsuda, Kazuyuki Niitsuma, Takashi Tamura, Takeshi Ueki, Hisashi Kokubo, Masayoshi WatanabeAbstract:The solubility and phase behavior of five Polyethers in 14 different room-temperature ionic liquids (ILs) were studied by changing the structures of Polyethers and the cations and anions in the ILs. Certain combinations of a polyether and an IL binary mixture exhibited lower critical solution temperature (LCST) phase behavior. The phase separation temperature (cloud point) was revealed to be sensitive to the aromaticity and alkyl chain length of the IL cations, the anionic Lewis basicities of the ILs and the polarity of the Polyethers. PEGE, poly(ethyl glycidyl ether).
Wayne R Litaker - One of the best experts on this subject based on the ideXlab platform.
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rapid extraction and identification of maitotoxin and ciguatoxin like toxins from caribbean and pacific gambierdiscus using a new functional bioassay
2016Co-Authors: Richard J. Lewis, Marco Inserra, William C Holland, Ransom D Hardison, Patricia A. Tester, Wayne R LitakerAbstract:Background Ciguatera is a circumtropical disease produced by polyether sodium channel toxins (ciguatoxins) that enter the marine food chain and accumulate in otherwise edible fish. Ciguatoxins, as well as potent water-soluble Polyethers known as maitotoxins, are produced by certain dinoflagellate species in the genus Gambierdiscus and Fukuyoa spp. in the Pacific but little is known of the potential of related Caribbean species to produce these toxins. Methods We established a simplified procedure for extracting polyether toxins from Gambierdiscus and Fukuyoa spp. based on the ciguatoxin rapid extraction method (CREM). Fractionated extracts from identified Pacific and Caribbean isolates were analysed using a functional bioassay that recorded intracellular calcium changes (Ca2+) in response to sample addition in SH-SY5Y cells. Maitotoxin directly elevated Ca2+i, while low levels of ciguatoxin-like toxins were detected using veratridine to enhance responses. Results We identified significant maitotoxin production in 11 of 12 isolates analysed, with 6 of 12 producing at least two forms of maitotoxin. In contrast, only 2 Caribbean isolates produced detectable levels of ciguatoxin-like activity despite a detection limit of >30 pM. Significant strain-dependent differences in the levels and types of ciguatoxins and maitotoxins produced by the same Gambierdiscus spp. were also identified. Conclusions The ability to rapidly identify polyether toxins produced by Gambierdiscus spp. in culture has the potential to distinguish ciguatoxin-producing species prior to large-scale culture and in naturally occurring blooms of Gambierdiscus and Fukuyoa spp. Our results have implications for the evaluation of ciguatera risk associated with Gambierdiscus and related species.
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rapid extraction and identification of maitotoxin and ciguatoxin like toxins from caribbean and pacific gambierdiscus using a new functional bioassay
2016Co-Authors: Richard J. Lewis, Marco Inserra, William C Holland, Ransom D Hardison, Patricia A. Tester, Irina Vetter, Wayne R LitakerAbstract:Background Ciguatera is a circumtropical disease produced by polyether sodium channel toxins (ciguatoxins) that enter the marine food chain and accumulate in otherwise edible fish. Ciguatoxins, as well as potent water-soluble Polyethers known as maitotoxins, are produced by certain dinoflagellate species in the genus Gambierdiscus and Fukuyoa spp. in the Pacific but little is known of the potential of related Caribbean species to produce these toxins.
Richard J. Lewis - One of the best experts on this subject based on the ideXlab platform.
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rapid extraction and identification of maitotoxin and ciguatoxin like toxins from caribbean and pacific gambierdiscus using a new functional bioassay
2016Co-Authors: Richard J. Lewis, Marco Inserra, William C Holland, Ransom D Hardison, Patricia A. Tester, Wayne R LitakerAbstract:Background Ciguatera is a circumtropical disease produced by polyether sodium channel toxins (ciguatoxins) that enter the marine food chain and accumulate in otherwise edible fish. Ciguatoxins, as well as potent water-soluble Polyethers known as maitotoxins, are produced by certain dinoflagellate species in the genus Gambierdiscus and Fukuyoa spp. in the Pacific but little is known of the potential of related Caribbean species to produce these toxins. Methods We established a simplified procedure for extracting polyether toxins from Gambierdiscus and Fukuyoa spp. based on the ciguatoxin rapid extraction method (CREM). Fractionated extracts from identified Pacific and Caribbean isolates were analysed using a functional bioassay that recorded intracellular calcium changes (Ca2+) in response to sample addition in SH-SY5Y cells. Maitotoxin directly elevated Ca2+i, while low levels of ciguatoxin-like toxins were detected using veratridine to enhance responses. Results We identified significant maitotoxin production in 11 of 12 isolates analysed, with 6 of 12 producing at least two forms of maitotoxin. In contrast, only 2 Caribbean isolates produced detectable levels of ciguatoxin-like activity despite a detection limit of >30 pM. Significant strain-dependent differences in the levels and types of ciguatoxins and maitotoxins produced by the same Gambierdiscus spp. were also identified. Conclusions The ability to rapidly identify polyether toxins produced by Gambierdiscus spp. in culture has the potential to distinguish ciguatoxin-producing species prior to large-scale culture and in naturally occurring blooms of Gambierdiscus and Fukuyoa spp. Our results have implications for the evaluation of ciguatera risk associated with Gambierdiscus and related species.
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rapid extraction and identification of maitotoxin and ciguatoxin like toxins from caribbean and pacific gambierdiscus using a new functional bioassay
2016Co-Authors: Richard J. Lewis, Marco Inserra, William C Holland, Ransom D Hardison, Patricia A. Tester, Irina Vetter, Wayne R LitakerAbstract:Background Ciguatera is a circumtropical disease produced by polyether sodium channel toxins (ciguatoxins) that enter the marine food chain and accumulate in otherwise edible fish. Ciguatoxins, as well as potent water-soluble Polyethers known as maitotoxins, are produced by certain dinoflagellate species in the genus Gambierdiscus and Fukuyoa spp. in the Pacific but little is known of the potential of related Caribbean species to produce these toxins.
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lonspray mass spectrometry of ciguatoxin 1 maitotoxin 2 and 3 and related marine polyether toxins
1994Co-Authors: Richard J. Lewis, Michael J. Holmes, Paul F Alewood, Alun JonesAbstract:A range of marine polyether toxins from dinoflagellates were analysed by ionspray mass spectrometry. Ciguatoxin‐1 ([M + H] m/z = 1,111.8) purified from several fish species yielded singly charged ions corresponding to the parent ion, sodium and HO adducts and ions for the loss of up to five HO molecules. Ciguatoxin‐1 was detected to 1 ng; however, interference from fish lipids precluded direct detection of ciguatoxin‐1 in crude extracts from fish flesh spiked with ciguatoxin‐1 at a level equivalent to 1.5 ng ciguatoxin‐1/g of extracted flesh. Maitotoxin‐2 yielded doubly and triply charged ions for sodium and potassium salts and likely possessed only one sulphate ester (M = 3,298 for the mono‐sodium salt). Maito‐toxin‐3, a recently isolated small maitotoxin, yielded singly charged ions including ions for the loss of one sulphate and up to four HO molecules. Maitotoxin‐3 is proposed to be a polyether compound possessing two sulphate esters (M = 1,060.5 for the disodium salt). Brevetoxin‐A ([M + H] m/z = 867.5) and bre‐vetoxin‐B ([M + H] m/z = 895.5) yielded singly charged ions corresponding to the parent ion, Na adducts and the loss of up to four HO molecules. Okadaic acid ([M + H] m/z = 805.5) yielded singly charged ions corresponding to the parent ion and ions for the loss of up to three HO molecules. A signal for M + 18 Da species that may represent [M + NH] was observed for ciguatoxin‐1, brevetoxin‐A and ‐B, and okadaic acid. For all Polyethers examined, the orifice potential influenced the relative intensity of the ions detected in a predictable manner. lonspray mass spectrometry provides a simple, sensitive means of identifying a range of marine polyether toxins, with the potential to form the basis of confirmatory assays for such toxins. © 1994 Wiley‐Liss, Inc.