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Setting exclusive relation
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2017-08-15T12:25:38.335Z
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2018-10-11T14:37:07.719Z
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cdrApp
2019-02-27T22:25:19.280Z
modifyDatastreamByValue
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cdrApp
2019-03-19T17:55:12.149Z
Trandon
Bender
Author
Department of Chemistry
College of Arts and Sciences
METHODS FOR THE SELECTIVE MODIFICATION OF CARBOHYDRATES AND NATURAL PRODUCTS
Selective modification of complex molecular scaffolds in the form of carbohydrates and natural products in a controllable way is a long-standing challenge. In carbohydrates, this problem results from the difficulty of activating carbon oxygen (C–O) bonds that are similar in reactivity making it difficult to differentiate between which bonds are activated. Natural products present a completely unique challenge in that they often contain disparate functional groups that present cross reactivity issues making activation of a natural product in a controllable way challenging. Each presents its own challenge, but the ability to perform selective modification of carbohydrates and natural products offers new routes to valuable chiral synthons from a renewable source and the opportunity to create new chemical space in molecular scaffolds that are often mined for biologically active drug candidates, respectively.
Fluoroarylborane-based catalysts (such as B(C6F5)3) are uniquely capable in this regard as they heterolytically activate Si–H bonds to generate an oxophilic silylium (R3Si+) equivalent along with a reducing borohydride (H–BR3–). Although silylium ions are notoriously oxophilic and aggressive electrophiles that would seemingly be a poor choice for carrying out selective chemistry on a complex molecule, much less one with diverse (often oxygenated) functionality, together these components enable the selective activation and reduction C–O bonds in carbohydrates and complex natural products. Imperative to the selective deoxygenation of carbohydrates was the realization that selective neighboring group participation results in chemoselective formation of cyclic intermediates which are reduced with high diastereoselectivity to generate chiral synthons. With the observation that cyclic intermediates guide selective activation in polyoxygenated substrates, we expanded this application to include selective allylic C–O bond reduction in linear styryl-carbohydrates which also relied on cyclic intermediates to achieve high levels of selectivity. Ultimately, neighboring group participation in styryl-carbohyrates was harnessed to realize carbon-carbon bond formation to generate carbocycles in a highly diastereoselective fashion where cyclic intermediates are again implicated in the highly selective transformations.
Investigating fluroarylborane-based catalyst activation of natural products required that addition of an exogenous phosphine Lewis base to modify the catalyst speciation and enable aggressive silylium ions to be harnessed for the selective modification of natural product scaffolds. Importantly, manipulation of the catalyst, the silane reagent, and the reaction conditions provide good control over which (and how) the functional groups are modified. The application of this methodology on complex bioactive compounds (natural products or drugs) thus provides a powerful tool for assessing how structural diversifications of these bioactive compounds correlates with bioactivity.
Spring 2017
2017
Chemistry
Biomass, Catalysis, Hydrosilylation, Lewis acid, Natural Products
eng
Doctor of Philosophy
Dissertation
University of North Carolina at Chapel Hill Graduate School
Degree granting institution
Chemistry
Michele
Gagne
Thesis advisor
Alex
Miller
Thesis advisor
Maurice
Brookhart
Thesis advisor
Joesph
Templeton
Thesis advisor
Eric
Brustad
Thesis advisor
text
Trandon
Bender
Author
Department of Chemistry
College of Arts and Sciences
METHODS FOR THE SELECTIVE MODIFICATION OF CARBOHYDRATES AND NATURAL PRODUCTS
Selective modification of complex molecular scaffolds in the form of carbohydrates and natural products in a controllable way is a long-standing challenge. In carbohydrates, this problem results from the difficulty of activating carbon oxygen (C–O) bonds that are similar in reactivity making it difficult to differentiate between which bonds are activated. Natural products present a completely unique challenge in that they often contain disparate functional groups that present cross reactivity issues making activation of a natural product in a controllable way challenging. Each presents its own challenge, but the ability to perform selective modification of carbohydrates and natural products offers new routes to valuable chiral synthons from a renewable source and the opportunity to create new chemical space in molecular scaffolds that are often mined for biologically active drug candidates, respectively.
Fluoroarylborane-based catalysts (such as B(C6F5)3) are uniquely capable in this regard as they heterolytically activate Si–H bonds to generate an oxophilic silylium (R3Si+) equivalent along with a reducing borohydride (H–BR3–). Although silylium ions are notoriously oxophilic and aggressive electrophiles that would seemingly be a poor choice for carrying out selective chemistry on a complex molecule, much less one with diverse (often oxygenated) functionality, together these components enable the selective activation and reduction C–O bonds in carbohydrates and complex natural products. Imperative to the selective deoxygenation of carbohydrates was the realization that selective neighboring group participation results in chemoselective formation of cyclic intermediates which are reduced with high diastereoselectivity to generate chiral synthons. With the observation that cyclic intermediates guide selective activation in polyoxygenated substrates, we expanded this application to include selective allylic C–O bond reduction in linear styryl-carbohydrates which also relied on cyclic intermediates to achieve high levels of selectivity. Ultimately, neighboring group participation in styryl-carbohyrates was harnessed to realize carbon-carbon bond formation to generate carbocycles in a highly diastereoselective fashion where cyclic intermediates are again implicated in the highly selective transformations.
Investigating fluroarylborane-based catalyst activation of natural products required that addition of an exogenous phosphine Lewis base to modify the catalyst speciation and enable aggressive silylium ions to be harnessed for the selective modification of natural product scaffolds. Importantly, manipulation of the catalyst, the silane reagent, and the reaction conditions provide good control over which (and how) the functional groups are modified. The application of this methodology on complex bioactive compounds (natural products or drugs) thus provides a powerful tool for assessing how structural diversifications of these bioactive compounds correlates with bioactivity.
Spring 2017
2017
Chemistry
Biomass
Catalysis
Hydrosilylation
Lewis acid
Natural Products
eng
Doctor of Philosophy
Dissertation
University of North Carolina at Chapel Hill Graduate School
Degree granting institution
Chemistry
Michele
Gagne
Thesis advisor
Alex
Miller
Thesis advisor
Maurice
Brookhart
Thesis advisor
Joesph
Templeton
Thesis advisor
Eric
Brustad
Thesis advisor
text
Trandon
Bender
Creator
Department of Chemistry
College of Arts and Sciences
METHODS FOR THE SELECTIVE MODIFICATION OF CARBOHYDRATES AND NATURAL
PRODUCTS
Selective modification of complex molecular scaffolds in the form of
carbohydrates and natural products in a controllable way is a long-standing challenge. In
carbohydrates, this problem results from the difficulty of activating carbon oxygen (C–O)
bonds that are similar in reactivity making it difficult to differentiate between which
bonds are activated. Natural products present a completely unique challenge in that they
often contain disparate functional groups that present cross reactivity issues making
activation of a natural product in a controllable way challenging. Each presents its own
challenge, but the ability to perform selective modification of carbohydrates and natural
products offers new routes to valuable chiral synthons from a renewable source and the
opportunity to create new chemical space in molecular scaffolds that are often mined for
biologically active drug candidates, respectively. Fluoroarylborane-based catalysts (such
as B(C6F5)3) are uniquely capable in this regard as they heterolytically activate Si–H
bonds to generate an oxophilic silylium (R3Si+) equivalent along with a reducing
borohydride (H–BR3–). Although silylium ions are notoriously oxophilic and aggressive
electrophiles that would seemingly be a poor choice for carrying out selective chemistry
on a complex molecule, much less one with diverse (often oxygenated) functionality,
together these components enable the selective activation and reduction C–O bonds in
carbohydrates and complex natural products. Imperative to the selective deoxygenation of
carbohydrates was the realization that selective neighboring group participation results
in chemoselective formation of cyclic intermediates which are reduced with high
diastereoselectivity to generate chiral synthons. With the observation that cyclic
intermediates guide selective activation in polyoxygenated substrates, we expanded this
application to include selective allylic C–O bond reduction in linear styryl-carbohydrates
which also relied on cyclic intermediates to achieve high levels of selectivity.
Ultimately, neighboring group participation in styryl-carbohyrates was harnessed to
realize carbon-carbon bond formation to generate carbocycles in a highly
diastereoselective fashion where cyclic intermediates are again implicated in the highly
selective transformations. Investigating fluroarylborane-based catalyst activation of
natural products required that addition of an exogenous phosphine Lewis base to modify the
catalyst speciation and enable aggressive silylium ions to be harnessed for the selective
modification of natural product scaffolds. Importantly, manipulation of the catalyst, the
silane reagent, and the reaction conditions provide good control over which (and how) the
functional groups are modified. The application of this methodology on complex bioactive
compounds (natural products or drugs) thus provides a powerful tool for assessing how
structural diversifications of these bioactive compounds correlates with
bioactivity.
Spring 2017
2017
Chemistry
Biomass Catalysis Hydrosilylation Lewis acid Natural
Products
eng
Doctor of Philosophy
Dissertation
University of North Carolina at Chapel Hill Graduate School
Degree granting
institution
Chemistry
Michele
Gagne
Thesis advisor
Alex
Miller
Thesis advisor
Maurice
Brookhart
Thesis advisor
Joesph
Templeton
Thesis advisor
Eric
Brustad
Thesis advisor
text
Trandon
Bender
Creator
Department of Chemistry
College of Arts and Sciences
METHODS FOR THE SELECTIVE MODIFICATION OF CARBOHYDRATES AND NATURAL PRODUCTS
Selective modification of complex molecular scaffolds in the form of carbohydrates and natural products in a controllable way is a long-standing challenge. In carbohydrates, this problem results from the difficulty of activating carbon oxygen (C–O) bonds that are similar in reactivity making it difficult to differentiate between which bonds are activated. Natural products present a completely unique challenge in that they often contain disparate functional groups that present cross reactivity issues making activation of a natural product in a controllable way challenging. Each presents its own challenge, but the ability to perform selective modification of carbohydrates and natural products offers new routes to valuable chiral synthons from a renewable source and the opportunity to create new chemical space in molecular scaffolds that are often mined for biologically active drug candidates, respectively. Fluoroarylborane-based catalysts (such as B(C6F5)3) are uniquely capable in this regard as they heterolytically activate Si–H bonds to generate an oxophilic silylium (R3Si+) equivalent along with a reducing borohydride (H–BR3–). Although silylium ions are notoriously oxophilic and aggressive electrophiles that would seemingly be a poor choice for carrying out selective chemistry on a complex molecule, much less one with diverse (often oxygenated) functionality, together these components enable the selective activation and reduction C–O bonds in carbohydrates and complex natural products. Imperative to the selective deoxygenation of carbohydrates was the realization that selective neighboring group participation results in chemoselective formation of cyclic intermediates which are reduced with high diastereoselectivity to generate chiral synthons. With the observation that cyclic intermediates guide selective activation in polyoxygenated substrates, we expanded this application to include selective allylic C–O bond reduction in linear styryl-carbohydrates which also relied on cyclic intermediates to achieve high levels of selectivity. Ultimately, neighboring group participation in styryl-carbohyrates was harnessed to realize carbon-carbon bond formation to generate carbocycles in a highly diastereoselective fashion where cyclic intermediates are again implicated in the highly selective transformations. Investigating fluroarylborane-based catalyst activation of natural products required that addition of an exogenous phosphine Lewis base to modify the catalyst speciation and enable aggressive silylium ions to be harnessed for the selective modification of natural product scaffolds. Importantly, manipulation of the catalyst, the silane reagent, and the reaction conditions provide good control over which (and how) the functional groups are modified. The application of this methodology on complex bioactive compounds (natural products or drugs) thus provides a powerful tool for assessing how structural diversifications of these bioactive compounds correlates with bioactivity.
Spring 2017
2017
Chemistry
Biomass Catalysis Hydrosilylation Lewis acid Natural Products
eng
Doctor of Philosophy
Dissertation
University of North Carolina at Chapel Hill Graduate School
Degree granting institution
Chemistry
Michele
Gagne
Thesis advisor
Alex
Miller
Thesis advisor
Maurice
Brookhart
Thesis advisor
Joesph
Templeton
Thesis advisor
Eric
Brustad
Thesis advisor
text
Trandon
Bender
Creator
Department of Chemistry
College of Arts and Sciences
METHODS FOR THE SELECTIVE MODIFICATION OF CARBOHYDRATES AND NATURAL PRODUCTS
Selective modification of complex molecular scaffolds in the form of carbohydrates and natural products in a controllable way is a long-standing challenge. In carbohydrates, this problem results from the difficulty of activating carbon oxygen (C–O) bonds that are similar in reactivity making it difficult to differentiate between which bonds are activated. Natural products present a completely unique challenge in that they often contain disparate functional groups that present cross reactivity issues making activation of a natural product in a controllable way challenging. Each presents its own challenge, but the ability to perform selective modification of carbohydrates and natural products offers new routes to valuable chiral synthons from a renewable source and the opportunity to create new chemical space in molecular scaffolds that are often mined for biologically active drug candidates, respectively. Fluoroarylborane-based catalysts (such as B(C6F5)3) are uniquely capable in this regard as they heterolytically activate Si–H bonds to generate an oxophilic silylium (R3Si+) equivalent along with a reducing borohydride (H–BR3–). Although silylium ions are notoriously oxophilic and aggressive electrophiles that would seemingly be a poor choice for carrying out selective chemistry on a complex molecule, much less one with diverse (often oxygenated) functionality, together these components enable the selective activation and reduction C–O bonds in carbohydrates and complex natural products. Imperative to the selective deoxygenation of carbohydrates was the realization that selective neighboring group participation results in chemoselective formation of cyclic intermediates which are reduced with high diastereoselectivity to generate chiral synthons. With the observation that cyclic intermediates guide selective activation in polyoxygenated substrates, we expanded this application to include selective allylic C–O bond reduction in linear styryl-carbohydrates which also relied on cyclic intermediates to achieve high levels of selectivity. Ultimately, neighboring group participation in styryl-carbohyrates was harnessed to realize carbon-carbon bond formation to generate carbocycles in a highly diastereoselective fashion where cyclic intermediates are again implicated in the highly selective transformations. Investigating fluroarylborane-based catalyst activation of natural products required that addition of an exogenous phosphine Lewis base to modify the catalyst speciation and enable aggressive silylium ions to be harnessed for the selective modification of natural product scaffolds. Importantly, manipulation of the catalyst, the silane reagent, and the reaction conditions provide good control over which (and how) the functional groups are modified. The application of this methodology on complex bioactive compounds (natural products or drugs) thus provides a powerful tool for assessing how structural diversifications of these bioactive compounds correlates with bioactivity.
2017-05
2017
Chemistry
Biomass Catalysis Hydrosilylation Lewis acid Natural Products
eng
Doctor of Philosophy
Dissertation
University of North Carolina at Chapel Hill Graduate School
Degree granting institution
Chemistry
Michele
Gagne
Thesis advisor
Alex
Miller
Thesis advisor
Maurice
Brookhart
Thesis advisor
Joesph
Templeton
Thesis advisor
Eric
Brustad
Thesis advisor
text
Trandon
Bender
Creator
Department of Chemistry
College of Arts and Sciences
METHODS FOR THE SELECTIVE MODIFICATION OF CARBOHYDRATES AND NATURAL PRODUCTS
Selective modification of complex molecular scaffolds in the form of carbohydrates and natural products in a controllable way is a long-standing challenge. In carbohydrates, this problem results from the difficulty of activating carbon oxygen (C–O) bonds that are similar in reactivity making it difficult to differentiate between which bonds are activated. Natural products present a completely unique challenge in that they often contain disparate functional groups that present cross reactivity issues making activation of a natural product in a controllable way challenging. Each presents its own challenge, but the ability to perform selective modification of carbohydrates and natural products offers new routes to valuable chiral synthons from a renewable source and the opportunity to create new chemical space in molecular scaffolds that are often mined for biologically active drug candidates, respectively. Fluoroarylborane-based catalysts (such as B(C6F5)3) are uniquely capable in this regard as they heterolytically activate Si–H bonds to generate an oxophilic silylium (R3Si+) equivalent along with a reducing borohydride (H–BR3–). Although silylium ions are notoriously oxophilic and aggressive electrophiles that would seemingly be a poor choice for carrying out selective chemistry on a complex molecule, much less one with diverse (often oxygenated) functionality, together these components enable the selective activation and reduction C–O bonds in carbohydrates and complex natural products. Imperative to the selective deoxygenation of carbohydrates was the realization that selective neighboring group participation results in chemoselective formation of cyclic intermediates which are reduced with high diastereoselectivity to generate chiral synthons. With the observation that cyclic intermediates guide selective activation in polyoxygenated substrates, we expanded this application to include selective allylic C–O bond reduction in linear styryl-carbohydrates which also relied on cyclic intermediates to achieve high levels of selectivity. Ultimately, neighboring group participation in styryl-carbohyrates was harnessed to realize carbon-carbon bond formation to generate carbocycles in a highly diastereoselective fashion where cyclic intermediates are again implicated in the highly selective transformations. Investigating fluroarylborane-based catalyst activation of natural products required that addition of an exogenous phosphine Lewis base to modify the catalyst speciation and enable aggressive silylium ions to be harnessed for the selective modification of natural product scaffolds. Importantly, manipulation of the catalyst, the silane reagent, and the reaction conditions provide good control over which (and how) the functional groups are modified. The application of this methodology on complex bioactive compounds (natural products or drugs) thus provides a powerful tool for assessing how structural diversifications of these bioactive compounds correlates with bioactivity.
2017
Chemistry
Biomass Catalysis Hydrosilylation Lewis acid Natural Products
eng
Doctor of Philosophy
Dissertation
University of North Carolina at Chapel Hill Graduate School
Degree granting institution
Chemistry
Michele
Gagne
Thesis advisor
Alex
Miller
Thesis advisor
Maurice
Brookhart
Thesis advisor
Joesph
Templeton
Thesis advisor
Eric
Brustad
Thesis advisor
text
2017-05
Trandon
Bender
Creator
Department of Chemistry
College of Arts and Sciences
METHODS FOR THE SELECTIVE MODIFICATION OF CARBOHYDRATES AND NATURAL PRODUCTS
Selective modification of complex molecular scaffolds in the form of carbohydrates and natural products in a controllable way is a long-standing challenge. In carbohydrates, this problem results from the difficulty of activating carbon oxygen (C–O) bonds that are similar in reactivity making it difficult to differentiate between which bonds are activated. Natural products present a completely unique challenge in that they often contain disparate functional groups that present cross reactivity issues making activation of a natural product in a controllable way challenging. Each presents its own challenge, but the ability to perform selective modification of carbohydrates and natural products offers new routes to valuable chiral synthons from a renewable source and the opportunity to create new chemical space in molecular scaffolds that are often mined for biologically active drug candidates, respectively. Fluoroarylborane-based catalysts (such as B(C6F5)3) are uniquely capable in this regard as they heterolytically activate Si–H bonds to generate an oxophilic silylium (R3Si+) equivalent along with a reducing borohydride (H–BR3–). Although silylium ions are notoriously oxophilic and aggressive electrophiles that would seemingly be a poor choice for carrying out selective chemistry on a complex molecule, much less one with diverse (often oxygenated) functionality, together these components enable the selective activation and reduction C–O bonds in carbohydrates and complex natural products. Imperative to the selective deoxygenation of carbohydrates was the realization that selective neighboring group participation results in chemoselective formation of cyclic intermediates which are reduced with high diastereoselectivity to generate chiral synthons. With the observation that cyclic intermediates guide selective activation in polyoxygenated substrates, we expanded this application to include selective allylic C–O bond reduction in linear styryl-carbohydrates which also relied on cyclic intermediates to achieve high levels of selectivity. Ultimately, neighboring group participation in styryl-carbohyrates was harnessed to realize carbon-carbon bond formation to generate carbocycles in a highly diastereoselective fashion where cyclic intermediates are again implicated in the highly selective transformations. Investigating fluroarylborane-based catalyst activation of natural products required that addition of an exogenous phosphine Lewis base to modify the catalyst speciation and enable aggressive silylium ions to be harnessed for the selective modification of natural product scaffolds. Importantly, manipulation of the catalyst, the silane reagent, and the reaction conditions provide good control over which (and how) the functional groups are modified. The application of this methodology on complex bioactive compounds (natural products or drugs) thus provides a powerful tool for assessing how structural diversifications of these bioactive compounds correlates with bioactivity.
2017
Chemistry
Biomass Catalysis Hydrosilylation Lewis acid Natural Products
eng
Doctor of Philosophy
Dissertation
University of North Carolina at Chapel Hill Graduate School
Degree granting institution
Chemistry
Michele
Gagne
Thesis advisor
Alex
Miller
Thesis advisor
Maurice
Brookhart
Thesis advisor
Joesph
Templeton
Thesis advisor
Eric
Brustad
Thesis advisor
text
2017-05
Trandon
Bender
Creator
Department of Chemistry
College of Arts and Sciences
METHODS FOR THE SELECTIVE MODIFICATION OF CARBOHYDRATES AND NATURAL PRODUCTS
Selective modification of complex molecular scaffolds in the form of carbohydrates and natural products in a controllable way is a long-standing challenge. In carbohydrates, this problem results from the difficulty of activating carbon oxygen (C–O) bonds that are similar in reactivity making it difficult to differentiate between which bonds are activated. Natural products present a completely unique challenge in that they often contain disparate functional groups that present cross reactivity issues making activation of a natural product in a controllable way challenging. Each presents its own challenge, but the ability to perform selective modification of carbohydrates and natural products offers new routes to valuable chiral synthons from a renewable source and the opportunity to create new chemical space in molecular scaffolds that are often mined for biologically active drug candidates, respectively. Fluoroarylborane-based catalysts (such as B(C6F5)3) are uniquely capable in this regard as they heterolytically activate Si–H bonds to generate an oxophilic silylium (R3Si+) equivalent along with a reducing borohydride (H–BR3–). Although silylium ions are notoriously oxophilic and aggressive electrophiles that would seemingly be a poor choice for carrying out selective chemistry on a complex molecule, much less one with diverse (often oxygenated) functionality, together these components enable the selective activation and reduction C–O bonds in carbohydrates and complex natural products. Imperative to the selective deoxygenation of carbohydrates was the realization that selective neighboring group participation results in chemoselective formation of cyclic intermediates which are reduced with high diastereoselectivity to generate chiral synthons. With the observation that cyclic intermediates guide selective activation in polyoxygenated substrates, we expanded this application to include selective allylic C–O bond reduction in linear styryl-carbohydrates which also relied on cyclic intermediates to achieve high levels of selectivity. Ultimately, neighboring group participation in styryl-carbohyrates was harnessed to realize carbon-carbon bond formation to generate carbocycles in a highly diastereoselective fashion where cyclic intermediates are again implicated in the highly selective transformations. Investigating fluroarylborane-based catalyst activation of natural products required that addition of an exogenous phosphine Lewis base to modify the catalyst speciation and enable aggressive silylium ions to be harnessed for the selective modification of natural product scaffolds. Importantly, manipulation of the catalyst, the silane reagent, and the reaction conditions provide good control over which (and how) the functional groups are modified. The application of this methodology on complex bioactive compounds (natural products or drugs) thus provides a powerful tool for assessing how structural diversifications of these bioactive compounds correlates with bioactivity.
2017
Chemistry
Biomass Catalysis Hydrosilylation Lewis acid Natural Products
eng
Doctor of Philosophy
Dissertation
University of North Carolina at Chapel Hill Graduate School
Degree granting institution
Chemistry
Michele
Gagne
Thesis advisor
Alex
Miller
Thesis advisor
Maurice
Brookhart
Thesis advisor
Joesph
Templeton
Thesis advisor
Eric
Brustad
Thesis advisor
text
2017-05
Trandon
Bender
Creator
Department of Chemistry
College of Arts and Sciences
METHODS FOR THE SELECTIVE MODIFICATION OF CARBOHYDRATES AND NATURAL PRODUCTS
Selective modification of complex molecular scaffolds in the form of carbohydrates and natural products in a controllable way is a long-standing challenge. In carbohydrates, this problem results from the difficulty of activating carbon oxygen (C–O) bonds that are similar in reactivity making it difficult to differentiate between which bonds are activated. Natural products present a completely unique challenge in that they often contain disparate functional groups that present cross reactivity issues making activation of a natural product in a controllable way challenging. Each presents its own challenge, but the ability to perform selective modification of carbohydrates and natural products offers new routes to valuable chiral synthons from a renewable source and the opportunity to create new chemical space in molecular scaffolds that are often mined for biologically active drug candidates, respectively. Fluoroarylborane-based catalysts (such as B(C6F5)3) are uniquely capable in this regard as they heterolytically activate Si–H bonds to generate an oxophilic silylium (R3Si+) equivalent along with a reducing borohydride (H–BR3–). Although silylium ions are notoriously oxophilic and aggressive electrophiles that would seemingly be a poor choice for carrying out selective chemistry on a complex molecule, much less one with diverse (often oxygenated) functionality, together these components enable the selective activation and reduction C–O bonds in carbohydrates and complex natural products. Imperative to the selective deoxygenation of carbohydrates was the realization that selective neighboring group participation results in chemoselective formation of cyclic intermediates which are reduced with high diastereoselectivity to generate chiral synthons. With the observation that cyclic intermediates guide selective activation in polyoxygenated substrates, we expanded this application to include selective allylic C–O bond reduction in linear styryl-carbohydrates which also relied on cyclic intermediates to achieve high levels of selectivity. Ultimately, neighboring group participation in styryl-carbohyrates was harnessed to realize carbon-carbon bond formation to generate carbocycles in a highly diastereoselective fashion where cyclic intermediates are again implicated in the highly selective transformations. Investigating fluroarylborane-based catalyst activation of natural products required that addition of an exogenous phosphine Lewis base to modify the catalyst speciation and enable aggressive silylium ions to be harnessed for the selective modification of natural product scaffolds. Importantly, manipulation of the catalyst, the silane reagent, and the reaction conditions provide good control over which (and how) the functional groups are modified. The application of this methodology on complex bioactive compounds (natural products or drugs) thus provides a powerful tool for assessing how structural diversifications of these bioactive compounds correlates with bioactivity.
2017
Chemistry
Biomass Catalysis Hydrosilylation Lewis acid Natural Products
eng
Doctor of Philosophy
Dissertation
University of North Carolina at Chapel Hill Graduate School
Degree granting institution
Chemistry
Michele
Gagne
Thesis advisor
Alex
Miller
Thesis advisor
Maurice
Brookhart
Thesis advisor
Joesph
Templeton
Thesis advisor
Eric
Brustad
Thesis advisor
text
2017-05
Trandon
Bender
Creator
Department of Chemistry
College of Arts and Sciences
METHODS FOR THE SELECTIVE MODIFICATION OF CARBOHYDRATES AND NATURAL PRODUCTS
Selective modification of complex molecular scaffolds in the form of carbohydrates and natural products in a controllable way is a long-standing challenge. In carbohydrates, this problem results from the difficulty of activating carbon oxygen (C–O) bonds that are similar in reactivity making it difficult to differentiate between which bonds are activated. Natural products present a completely unique challenge in that they often contain disparate functional groups that present cross reactivity issues making activation of a natural product in a controllable way challenging. Each presents its own challenge, but the ability to perform selective modification of carbohydrates and natural products offers new routes to valuable chiral synthons from a renewable source and the opportunity to create new chemical space in molecular scaffolds that are often mined for biologically active drug candidates, respectively. Fluoroarylborane-based catalysts (such as B(C6F5)3) are uniquely capable in this regard as they heterolytically activate Si–H bonds to generate an oxophilic silylium (R3Si+) equivalent along with a reducing borohydride (H–BR3–). Although silylium ions are notoriously oxophilic and aggressive electrophiles that would seemingly be a poor choice for carrying out selective chemistry on a complex molecule, much less one with diverse (often oxygenated) functionality, together these components enable the selective activation and reduction C–O bonds in carbohydrates and complex natural products. Imperative to the selective deoxygenation of carbohydrates was the realization that selective neighboring group participation results in chemoselective formation of cyclic intermediates which are reduced with high diastereoselectivity to generate chiral synthons. With the observation that cyclic intermediates guide selective activation in polyoxygenated substrates, we expanded this application to include selective allylic C–O bond reduction in linear styryl-carbohydrates which also relied on cyclic intermediates to achieve high levels of selectivity. Ultimately, neighboring group participation in styryl-carbohyrates was harnessed to realize carbon-carbon bond formation to generate carbocycles in a highly diastereoselective fashion where cyclic intermediates are again implicated in the highly selective transformations. Investigating fluroarylborane-based catalyst activation of natural products required that addition of an exogenous phosphine Lewis base to modify the catalyst speciation and enable aggressive silylium ions to be harnessed for the selective modification of natural product scaffolds. Importantly, manipulation of the catalyst, the silane reagent, and the reaction conditions provide good control over which (and how) the functional groups are modified. The application of this methodology on complex bioactive compounds (natural products or drugs) thus provides a powerful tool for assessing how structural diversifications of these bioactive compounds correlates with bioactivity.
2017
Chemistry
Biomass Catalysis Hydrosilylation Lewis acid Natural Products
eng
Doctor of Philosophy
Dissertation
University of North Carolina at Chapel Hill Graduate School
Degree granting institution
Chemistry
Michel
Gagne
Thesis advisor
Alexander
Miller
Thesis advisor
Maurice
Brookhart
Thesis advisor
Joseph
Templeton
Thesis advisor
Eric
Brustad
Thesis advisor
text
2017-05
Trandon
Bender
Creator
Department of Chemistry
College of Arts and Sciences
METHODS FOR THE SELECTIVE MODIFICATION OF CARBOHYDRATES AND NATURAL PRODUCTS
Selective modification of complex molecular scaffolds in the form of carbohydrates and natural products in a controllable way is a long-standing challenge. In carbohydrates, this problem results from the difficulty of activating carbon oxygen (C–O) bonds that are similar in reactivity making it difficult to differentiate between which bonds are activated. Natural products present a completely unique challenge in that they often contain disparate functional groups that present cross reactivity issues making activation of a natural product in a controllable way challenging. Each presents its own challenge, but the ability to perform selective modification of carbohydrates and natural products offers new routes to valuable chiral synthons from a renewable source and the opportunity to create new chemical space in molecular scaffolds that are often mined for biologically active drug candidates, respectively. Fluoroarylborane-based catalysts (such as B(C6F5)3) are uniquely capable in this regard as they heterolytically activate Si–H bonds to generate an oxophilic silylium (R3Si+) equivalent along with a reducing borohydride (H–BR3–). Although silylium ions are notoriously oxophilic and aggressive electrophiles that would seemingly be a poor choice for carrying out selective chemistry on a complex molecule, much less one with diverse (often oxygenated) functionality, together these components enable the selective activation and reduction C–O bonds in carbohydrates and complex natural products. Imperative to the selective deoxygenation of carbohydrates was the realization that selective neighboring group participation results in chemoselective formation of cyclic intermediates which are reduced with high diastereoselectivity to generate chiral synthons. With the observation that cyclic intermediates guide selective activation in polyoxygenated substrates, we expanded this application to include selective allylic C–O bond reduction in linear styryl-carbohydrates which also relied on cyclic intermediates to achieve high levels of selectivity. Ultimately, neighboring group participation in styryl-carbohyrates was harnessed to realize carbon-carbon bond formation to generate carbocycles in a highly diastereoselective fashion where cyclic intermediates are again implicated in the highly selective transformations. Investigating fluroarylborane-based catalyst activation of natural products required that addition of an exogenous phosphine Lewis base to modify the catalyst speciation and enable aggressive silylium ions to be harnessed for the selective modification of natural product scaffolds. Importantly, manipulation of the catalyst, the silane reagent, and the reaction conditions provide good control over which (and how) the functional groups are modified. The application of this methodology on complex bioactive compounds (natural products or drugs) thus provides a powerful tool for assessing how structural diversifications of these bioactive compounds correlates with bioactivity.
2017
Chemistry
Biomass Catalysis Hydrosilylation Lewis acid Natural Products
eng
Doctor of Philosophy
Dissertation
University of North Carolina at Chapel Hill Graduate School
Degree granting institution
Chemistry
Michel
Gagne
Thesis advisor
Alexander
Miller
Thesis advisor
Maurice
Brookhart
Thesis advisor
Joseph
Templeton
Thesis advisor
Eric
Brustad
Thesis advisor
text
2017-05
Trandon
Bender
Creator
Department of Chemistry
College of Arts and Sciences
METHODS FOR THE SELECTIVE MODIFICATION OF CARBOHYDRATES AND NATURAL PRODUCTS
Selective modification of complex molecular scaffolds in the form of carbohydrates and natural products in a controllable way is a long-standing challenge. In carbohydrates, this problem results from the difficulty of activating carbon oxygen (C–O) bonds that are similar in reactivity making it difficult to differentiate between which bonds are activated. Natural products present a completely unique challenge in that they often contain disparate functional groups that present cross reactivity issues making activation of a natural product in a controllable way challenging. Each presents its own challenge, but the ability to perform selective modification of carbohydrates and natural products offers new routes to valuable chiral synthons from a renewable source and the opportunity to create new chemical space in molecular scaffolds that are often mined for biologically active drug candidates, respectively. Fluoroarylborane-based catalysts (such as B(C6F5)3) are uniquely capable in this regard as they heterolytically activate Si–H bonds to generate an oxophilic silylium (R3Si+) equivalent along with a reducing borohydride (H–BR3–). Although silylium ions are notoriously oxophilic and aggressive electrophiles that would seemingly be a poor choice for carrying out selective chemistry on a complex molecule, much less one with diverse (often oxygenated) functionality, together these components enable the selective activation and reduction C–O bonds in carbohydrates and complex natural products. Imperative to the selective deoxygenation of carbohydrates was the realization that selective neighboring group participation results in chemoselective formation of cyclic intermediates which are reduced with high diastereoselectivity to generate chiral synthons. With the observation that cyclic intermediates guide selective activation in polyoxygenated substrates, we expanded this application to include selective allylic C–O bond reduction in linear styryl-carbohydrates which also relied on cyclic intermediates to achieve high levels of selectivity. Ultimately, neighboring group participation in styryl-carbohyrates was harnessed to realize carbon-carbon bond formation to generate carbocycles in a highly diastereoselective fashion where cyclic intermediates are again implicated in the highly selective transformations. Investigating fluroarylborane-based catalyst activation of natural products required that addition of an exogenous phosphine Lewis base to modify the catalyst speciation and enable aggressive silylium ions to be harnessed for the selective modification of natural product scaffolds. Importantly, manipulation of the catalyst, the silane reagent, and the reaction conditions provide good control over which (and how) the functional groups are modified. The application of this methodology on complex bioactive compounds (natural products or drugs) thus provides a powerful tool for assessing how structural diversifications of these bioactive compounds correlates with bioactivity.
2017
Chemistry
Biomass Catalysis Hydrosilylation Lewis acid Natural Products
eng
Doctor of Philosophy
Dissertation
University of North Carolina at Chapel Hill Graduate School
Degree granting institution
Chemistry
Michele
Gagne
Thesis advisor
Alex
Miller
Thesis advisor
Maurice
Brookhart
Thesis advisor
Joesph
Templeton
Thesis advisor
Eric
Brustad
Thesis advisor
text
2017-05
Trandon
Bender
Creator
Department of Chemistry
College of Arts and Sciences
METHODS FOR THE SELECTIVE MODIFICATION OF CARBOHYDRATES AND NATURAL PRODUCTS
Selective modification of complex molecular scaffolds in the form of carbohydrates and natural products in a controllable way is a long-standing challenge. In carbohydrates, this problem results from the difficulty of activating carbon oxygen (C–O) bonds that are similar in reactivity making it difficult to differentiate between which bonds are activated. Natural products present a completely unique challenge in that they often contain disparate functional groups that present cross reactivity issues making activation of a natural product in a controllable way challenging. Each presents its own challenge, but the ability to perform selective modification of carbohydrates and natural products offers new routes to valuable chiral synthons from a renewable source and the opportunity to create new chemical space in molecular scaffolds that are often mined for biologically active drug candidates, respectively. Fluoroarylborane-based catalysts (such as B(C6F5)3) are uniquely capable in this regard as they heterolytically activate Si–H bonds to generate an oxophilic silylium (R3Si+) equivalent along with a reducing borohydride (H–BR3–). Although silylium ions are notoriously oxophilic and aggressive electrophiles that would seemingly be a poor choice for carrying out selective chemistry on a complex molecule, much less one with diverse (often oxygenated) functionality, together these components enable the selective activation and reduction C–O bonds in carbohydrates and complex natural products. Imperative to the selective deoxygenation of carbohydrates was the realization that selective neighboring group participation results in chemoselective formation of cyclic intermediates which are reduced with high diastereoselectivity to generate chiral synthons. With the observation that cyclic intermediates guide selective activation in polyoxygenated substrates, we expanded this application to include selective allylic C–O bond reduction in linear styryl-carbohydrates which also relied on cyclic intermediates to achieve high levels of selectivity. Ultimately, neighboring group participation in styryl-carbohyrates was harnessed to realize carbon-carbon bond formation to generate carbocycles in a highly diastereoselective fashion where cyclic intermediates are again implicated in the highly selective transformations. Investigating fluroarylborane-based catalyst activation of natural products required that addition of an exogenous phosphine Lewis base to modify the catalyst speciation and enable aggressive silylium ions to be harnessed for the selective modification of natural product scaffolds. Importantly, manipulation of the catalyst, the silane reagent, and the reaction conditions provide good control over which (and how) the functional groups are modified. The application of this methodology on complex bioactive compounds (natural products or drugs) thus provides a powerful tool for assessing how structural diversifications of these bioactive compounds correlates with bioactivity.
2017
Chemistry
Biomass Catalysis Hydrosilylation Lewis acid Natural Products
eng
Doctor of Philosophy
Dissertation
Chemistry
Michel
Gagne
Thesis advisor
Alexander
Miller
Thesis advisor
Maurice
Brookhart
Thesis advisor
Joseph
Templeton
Thesis advisor
Eric
Brustad
Thesis advisor
text
2017-05
University of North Carolina at Chapel Hill
Degree granting institution
Trandon
Bender
Creator
Department of Chemistry
College of Arts and Sciences
METHODS FOR THE SELECTIVE MODIFICATION OF CARBOHYDRATES AND NATURAL PRODUCTS
Selective modification of complex molecular scaffolds in the form of carbohydrates and natural products in a controllable way is a long-standing challenge. In carbohydrates, this problem results from the difficulty of activating carbon oxygen (C–O) bonds that are similar in reactivity making it difficult to differentiate between which bonds are activated. Natural products present a completely unique challenge in that they often contain disparate functional groups that present cross reactivity issues making activation of a natural product in a controllable way challenging. Each presents its own challenge, but the ability to perform selective modification of carbohydrates and natural products offers new routes to valuable chiral synthons from a renewable source and the opportunity to create new chemical space in molecular scaffolds that are often mined for biologically active drug candidates, respectively. Fluoroarylborane-based catalysts (such as B(C6F5)3) are uniquely capable in this regard as they heterolytically activate Si–H bonds to generate an oxophilic silylium (R3Si+) equivalent along with a reducing borohydride (H–BR3–). Although silylium ions are notoriously oxophilic and aggressive electrophiles that would seemingly be a poor choice for carrying out selective chemistry on a complex molecule, much less one with diverse (often oxygenated) functionality, together these components enable the selective activation and reduction C–O bonds in carbohydrates and complex natural products. Imperative to the selective deoxygenation of carbohydrates was the realization that selective neighboring group participation results in chemoselective formation of cyclic intermediates which are reduced with high diastereoselectivity to generate chiral synthons. With the observation that cyclic intermediates guide selective activation in polyoxygenated substrates, we expanded this application to include selective allylic C–O bond reduction in linear styryl-carbohydrates which also relied on cyclic intermediates to achieve high levels of selectivity. Ultimately, neighboring group participation in styryl-carbohyrates was harnessed to realize carbon-carbon bond formation to generate carbocycles in a highly diastereoselective fashion where cyclic intermediates are again implicated in the highly selective transformations. Investigating fluroarylborane-based catalyst activation of natural products required that addition of an exogenous phosphine Lewis base to modify the catalyst speciation and enable aggressive silylium ions to be harnessed for the selective modification of natural product scaffolds. Importantly, manipulation of the catalyst, the silane reagent, and the reaction conditions provide good control over which (and how) the functional groups are modified. The application of this methodology on complex bioactive compounds (natural products or drugs) thus provides a powerful tool for assessing how structural diversifications of these bioactive compounds correlates with bioactivity.
2017
Chemistry
Biomass Catalysis Hydrosilylation Lewis acid Natural Products
eng
Doctor of Philosophy
Dissertation
University of North Carolina at Chapel Hill Graduate School
Degree granting institution
Chemistry
Michele
Gagne
Thesis advisor
Alex
Miller
Thesis advisor
Maurice
Brookhart
Thesis advisor
Joesph
Templeton
Thesis advisor
Eric
Brustad
Thesis advisor
text
2017-05
Trandon
Bender
Creator
Department of Chemistry
College of Arts and Sciences
METHODS FOR THE SELECTIVE MODIFICATION OF CARBOHYDRATES AND NATURAL PRODUCTS
Selective modification of complex molecular scaffolds in the form of carbohydrates and natural products in a controllable way is a long-standing challenge. In carbohydrates, this problem results from the difficulty of activating carbon oxygen (C–O) bonds that are similar in reactivity making it difficult to differentiate between which bonds are activated. Natural products present a completely unique challenge in that they often contain disparate functional groups that present cross reactivity issues making activation of a natural product in a controllable way challenging. Each presents its own challenge, but the ability to perform selective modification of carbohydrates and natural products offers new routes to valuable chiral synthons from a renewable source and the opportunity to create new chemical space in molecular scaffolds that are often mined for biologically active drug candidates, respectively. Fluoroarylborane-based catalysts (such as B(C6F5)3) are uniquely capable in this regard as they heterolytically activate Si–H bonds to generate an oxophilic silylium (R3Si+) equivalent along with a reducing borohydride (H–BR3–). Although silylium ions are notoriously oxophilic and aggressive electrophiles that would seemingly be a poor choice for carrying out selective chemistry on a complex molecule, much less one with diverse (often oxygenated) functionality, together these components enable the selective activation and reduction C–O bonds in carbohydrates and complex natural products. Imperative to the selective deoxygenation of carbohydrates was the realization that selective neighboring group participation results in chemoselective formation of cyclic intermediates which are reduced with high diastereoselectivity to generate chiral synthons. With the observation that cyclic intermediates guide selective activation in polyoxygenated substrates, we expanded this application to include selective allylic C–O bond reduction in linear styryl-carbohydrates which also relied on cyclic intermediates to achieve high levels of selectivity. Ultimately, neighboring group participation in styryl-carbohyrates was harnessed to realize carbon-carbon bond formation to generate carbocycles in a highly diastereoselective fashion where cyclic intermediates are again implicated in the highly selective transformations. Investigating fluroarylborane-based catalyst activation of natural products required that addition of an exogenous phosphine Lewis base to modify the catalyst speciation and enable aggressive silylium ions to be harnessed for the selective modification of natural product scaffolds. Importantly, manipulation of the catalyst, the silane reagent, and the reaction conditions provide good control over which (and how) the functional groups are modified. The application of this methodology on complex bioactive compounds (natural products or drugs) thus provides a powerful tool for assessing how structural diversifications of these bioactive compounds correlates with bioactivity.
2017
Chemistry
Biomass Catalysis Hydrosilylation Lewis acid Natural Products
eng
Doctor of Philosophy
Dissertation
University of North Carolina at Chapel Hill Graduate School
Degree granting institution
Chemistry
Michele
Gagne
Thesis advisor
Alex
Miller
Thesis advisor
Maurice
Brookhart
Thesis advisor
Joesph
Templeton
Thesis advisor
Eric
Brustad
Thesis advisor
text
2017-05
Trandon
Bender
Creator
Department of Chemistry
College of Arts and Sciences
METHODS FOR THE SELECTIVE MODIFICATION OF CARBOHYDRATES AND NATURAL PRODUCTS
Selective modification of complex molecular scaffolds in the form of carbohydrates and natural products in a controllable way is a long-standing challenge. In carbohydrates, this problem results from the difficulty of activating carbon oxygen (C–O) bonds that are similar in reactivity making it difficult to differentiate between which bonds are activated. Natural products present a completely unique challenge in that they often contain disparate functional groups that present cross reactivity issues making activation of a natural product in a controllable way challenging. Each presents its own challenge, but the ability to perform selective modification of carbohydrates and natural products offers new routes to valuable chiral synthons from a renewable source and the opportunity to create new chemical space in molecular scaffolds that are often mined for biologically active drug candidates, respectively. Fluoroarylborane-based catalysts (such as B(C6F5)3) are uniquely capable in this regard as they heterolytically activate Si–H bonds to generate an oxophilic silylium (R3Si+) equivalent along with a reducing borohydride (H–BR3–). Although silylium ions are notoriously oxophilic and aggressive electrophiles that would seemingly be a poor choice for carrying out selective chemistry on a complex molecule, much less one with diverse (often oxygenated) functionality, together these components enable the selective activation and reduction C–O bonds in carbohydrates and complex natural products. Imperative to the selective deoxygenation of carbohydrates was the realization that selective neighboring group participation results in chemoselective formation of cyclic intermediates which are reduced with high diastereoselectivity to generate chiral synthons. With the observation that cyclic intermediates guide selective activation in polyoxygenated substrates, we expanded this application to include selective allylic C–O bond reduction in linear styryl-carbohydrates which also relied on cyclic intermediates to achieve high levels of selectivity. Ultimately, neighboring group participation in styryl-carbohyrates was harnessed to realize carbon-carbon bond formation to generate carbocycles in a highly diastereoselective fashion where cyclic intermediates are again implicated in the highly selective transformations. Investigating fluroarylborane-based catalyst activation of natural products required that addition of an exogenous phosphine Lewis base to modify the catalyst speciation and enable aggressive silylium ions to be harnessed for the selective modification of natural product scaffolds. Importantly, manipulation of the catalyst, the silane reagent, and the reaction conditions provide good control over which (and how) the functional groups are modified. The application of this methodology on complex bioactive compounds (natural products or drugs) thus provides a powerful tool for assessing how structural diversifications of these bioactive compounds correlates with bioactivity.
2017
Chemistry
Biomass Catalysis Hydrosilylation Lewis acid Natural Products
eng
Doctor of Philosophy
Dissertation
University of North Carolina at Chapel Hill Graduate School
Degree granting institution
Chemistry
Michele
Gagne
Thesis advisor
Alex
Miller
Thesis advisor
Maurice
Brookhart
Thesis advisor
Joesph
Templeton
Thesis advisor
Eric
Brustad
Thesis advisor
text
2017-05
Trandon
Bender
Creator
Department of Chemistry
College of Arts and Sciences
METHODS FOR THE SELECTIVE MODIFICATION OF CARBOHYDRATES AND NATURAL PRODUCTS
Selective modification of complex molecular scaffolds in the form of carbohydrates and natural products in a controllable way is a long-standing challenge. In carbohydrates, this problem results from the difficulty of activating carbon oxygen (C–O) bonds that are similar in reactivity making it difficult to differentiate between which bonds are activated. Natural products present a completely unique challenge in that they often contain disparate functional groups that present cross reactivity issues making activation of a natural product in a controllable way challenging. Each presents its own challenge, but the ability to perform selective modification of carbohydrates and natural products offers new routes to valuable chiral synthons from a renewable source and the opportunity to create new chemical space in molecular scaffolds that are often mined for biologically active drug candidates, respectively. Fluoroarylborane-based catalysts (such as B(C6F5)3) are uniquely capable in this regard as they heterolytically activate Si–H bonds to generate an oxophilic silylium (R3Si+) equivalent along with a reducing borohydride (H–BR3–). Although silylium ions are notoriously oxophilic and aggressive electrophiles that would seemingly be a poor choice for carrying out selective chemistry on a complex molecule, much less one with diverse (often oxygenated) functionality, together these components enable the selective activation and reduction C–O bonds in carbohydrates and complex natural products. Imperative to the selective deoxygenation of carbohydrates was the realization that selective neighboring group participation results in chemoselective formation of cyclic intermediates which are reduced with high diastereoselectivity to generate chiral synthons. With the observation that cyclic intermediates guide selective activation in polyoxygenated substrates, we expanded this application to include selective allylic C–O bond reduction in linear styryl-carbohydrates which also relied on cyclic intermediates to achieve high levels of selectivity. Ultimately, neighboring group participation in styryl-carbohyrates was harnessed to realize carbon-carbon bond formation to generate carbocycles in a highly diastereoselective fashion where cyclic intermediates are again implicated in the highly selective transformations. Investigating fluroarylborane-based catalyst activation of natural products required that addition of an exogenous phosphine Lewis base to modify the catalyst speciation and enable aggressive silylium ions to be harnessed for the selective modification of natural product scaffolds. Importantly, manipulation of the catalyst, the silane reagent, and the reaction conditions provide good control over which (and how) the functional groups are modified. The application of this methodology on complex bioactive compounds (natural products or drugs) thus provides a powerful tool for assessing how structural diversifications of these bioactive compounds correlates with bioactivity.
2017
Chemistry
Biomass Catalysis Hydrosilylation Lewis acid Natural Products
eng
Doctor of Philosophy
Dissertation
Chemistry
Michel
Gagne
Thesis advisor
Alexander
Miller
Thesis advisor
Maurice
Brookhart
Thesis advisor
Joseph
Templeton
Thesis advisor
Eric
Brustad
Thesis advisor
text
2017-05
University of North Carolina at Chapel Hill
Degree granting institution
Trandon
Bender
Creator
Department of Chemistry
College of Arts and Sciences
METHODS FOR THE SELECTIVE MODIFICATION OF CARBOHYDRATES AND NATURAL PRODUCTS
Selective modification of complex molecular scaffolds in the form of carbohydrates and natural products in a controllable way is a long-standing challenge. In carbohydrates, this problem results from the difficulty of activating carbon oxygen (C–O) bonds that are similar in reactivity making it difficult to differentiate between which bonds are activated. Natural products present a completely unique challenge in that they often contain disparate functional groups that present cross reactivity issues making activation of a natural product in a controllable way challenging. Each presents its own challenge, but the ability to perform selective modification of carbohydrates and natural products offers new routes to valuable chiral synthons from a renewable source and the opportunity to create new chemical space in molecular scaffolds that are often mined for biologically active drug candidates, respectively. Fluoroarylborane-based catalysts (such as B(C6F5)3) are uniquely capable in this regard as they heterolytically activate Si–H bonds to generate an oxophilic silylium (R3Si+) equivalent along with a reducing borohydride (H–BR3–). Although silylium ions are notoriously oxophilic and aggressive electrophiles that would seemingly be a poor choice for carrying out selective chemistry on a complex molecule, much less one with diverse (often oxygenated) functionality, together these components enable the selective activation and reduction C–O bonds in carbohydrates and complex natural products. Imperative to the selective deoxygenation of carbohydrates was the realization that selective neighboring group participation results in chemoselective formation of cyclic intermediates which are reduced with high diastereoselectivity to generate chiral synthons. With the observation that cyclic intermediates guide selective activation in polyoxygenated substrates, we expanded this application to include selective allylic C–O bond reduction in linear styryl-carbohydrates which also relied on cyclic intermediates to achieve high levels of selectivity. Ultimately, neighboring group participation in styryl-carbohyrates was harnessed to realize carbon-carbon bond formation to generate carbocycles in a highly diastereoselective fashion where cyclic intermediates are again implicated in the highly selective transformations. Investigating fluroarylborane-based catalyst activation of natural products required that addition of an exogenous phosphine Lewis base to modify the catalyst speciation and enable aggressive silylium ions to be harnessed for the selective modification of natural product scaffolds. Importantly, manipulation of the catalyst, the silane reagent, and the reaction conditions provide good control over which (and how) the functional groups are modified. The application of this methodology on complex bioactive compounds (natural products or drugs) thus provides a powerful tool for assessing how structural diversifications of these bioactive compounds correlates with bioactivity.
2017
Chemistry
Biomass Catalysis Hydrosilylation Lewis acid Natural Products
eng
Doctor of Philosophy
Dissertation
University of North Carolina at Chapel Hill Graduate School
Degree granting institution
Chemistry
Michel
Gagne
Thesis advisor
Alexander
Miller
Thesis advisor
Maurice
Brookhart
Thesis advisor
Joseph
Templeton
Thesis advisor
Eric
Brustad
Thesis advisor
text
2017-05
Trandon
Bender
Creator
Department of Chemistry
College of Arts and Sciences
METHODS FOR THE SELECTIVE MODIFICATION OF CARBOHYDRATES AND NATURAL PRODUCTS
Selective modification of complex molecular scaffolds in the form of carbohydrates and natural products in a controllable way is a long-standing challenge. In carbohydrates, this problem results from the difficulty of activating carbon oxygen (C–O) bonds that are similar in reactivity making it difficult to differentiate between which bonds are activated. Natural products present a completely unique challenge in that they often contain disparate functional groups that present cross reactivity issues making activation of a natural product in a controllable way challenging. Each presents its own challenge, but the ability to perform selective modification of carbohydrates and natural products offers new routes to valuable chiral synthons from a renewable source and the opportunity to create new chemical space in molecular scaffolds that are often mined for biologically active drug candidates, respectively. Fluoroarylborane-based catalysts (such as B(C6F5)3) are uniquely capable in this regard as they heterolytically activate Si–H bonds to generate an oxophilic silylium (R3Si+) equivalent along with a reducing borohydride (H–BR3–). Although silylium ions are notoriously oxophilic and aggressive electrophiles that would seemingly be a poor choice for carrying out selective chemistry on a complex molecule, much less one with diverse (often oxygenated) functionality, together these components enable the selective activation and reduction C–O bonds in carbohydrates and complex natural products. Imperative to the selective deoxygenation of carbohydrates was the realization that selective neighboring group participation results in chemoselective formation of cyclic intermediates which are reduced with high diastereoselectivity to generate chiral synthons. With the observation that cyclic intermediates guide selective activation in polyoxygenated substrates, we expanded this application to include selective allylic C–O bond reduction in linear styryl-carbohydrates which also relied on cyclic intermediates to achieve high levels of selectivity. Ultimately, neighboring group participation in styryl-carbohyrates was harnessed to realize carbon-carbon bond formation to generate carbocycles in a highly diastereoselective fashion where cyclic intermediates are again implicated in the highly selective transformations. Investigating fluroarylborane-based catalyst activation of natural products required that addition of an exogenous phosphine Lewis base to modify the catalyst speciation and enable aggressive silylium ions to be harnessed for the selective modification of natural product scaffolds. Importantly, manipulation of the catalyst, the silane reagent, and the reaction conditions provide good control over which (and how) the functional groups are modified. The application of this methodology on complex bioactive compounds (natural products or drugs) thus provides a powerful tool for assessing how structural diversifications of these bioactive compounds correlates with bioactivity.
2017
Chemistry
Biomass Catalysis Hydrosilylation Lewis acid Natural Products
eng
Doctor of Philosophy
Dissertation
University of North Carolina at Chapel Hill Graduate School
Degree granting institution
Chemistry
Michel
Gagne
Thesis advisor
Alexander
Miller
Thesis advisor
Maurice
Brookhart
Thesis advisor
Joseph
Templeton
Thesis advisor
Eric
Brustad
Thesis advisor
text
2017-05
Trandon
Bender
Creator
Department of Chemistry
College of Arts and Sciences
METHODS FOR THE SELECTIVE MODIFICATION OF CARBOHYDRATES AND NATURAL PRODUCTS
Selective modification of complex molecular scaffolds in the form of carbohydrates and natural products in a controllable way is a long-standing challenge. In carbohydrates, this problem results from the difficulty of activating carbon oxygen (C–O) bonds that are similar in reactivity making it difficult to differentiate between which bonds are activated. Natural products present a completely unique challenge in that they often contain disparate functional groups that present cross reactivity issues making activation of a natural product in a controllable way challenging. Each presents its own challenge, but the ability to perform selective modification of carbohydrates and natural products offers new routes to valuable chiral synthons from a renewable source and the opportunity to create new chemical space in molecular scaffolds that are often mined for biologically active drug candidates, respectively. Fluoroarylborane-based catalysts (such as B(C6F5)3) are uniquely capable in this regard as they heterolytically activate Si–H bonds to generate an oxophilic silylium (R3Si+) equivalent along with a reducing borohydride (H–BR3–). Although silylium ions are notoriously oxophilic and aggressive electrophiles that would seemingly be a poor choice for carrying out selective chemistry on a complex molecule, much less one with diverse (often oxygenated) functionality, together these components enable the selective activation and reduction C–O bonds in carbohydrates and complex natural products. Imperative to the selective deoxygenation of carbohydrates was the realization that selective neighboring group participation results in chemoselective formation of cyclic intermediates which are reduced with high diastereoselectivity to generate chiral synthons. With the observation that cyclic intermediates guide selective activation in polyoxygenated substrates, we expanded this application to include selective allylic C–O bond reduction in linear styryl-carbohydrates which also relied on cyclic intermediates to achieve high levels of selectivity. Ultimately, neighboring group participation in styryl-carbohyrates was harnessed to realize carbon-carbon bond formation to generate carbocycles in a highly diastereoselective fashion where cyclic intermediates are again implicated in the highly selective transformations. Investigating fluroarylborane-based catalyst activation of natural products required that addition of an exogenous phosphine Lewis base to modify the catalyst speciation and enable aggressive silylium ions to be harnessed for the selective modification of natural product scaffolds. Importantly, manipulation of the catalyst, the silane reagent, and the reaction conditions provide good control over which (and how) the functional groups are modified. The application of this methodology on complex bioactive compounds (natural products or drugs) thus provides a powerful tool for assessing how structural diversifications of these bioactive compounds correlates with bioactivity.
2017
Chemistry
Biomass Catalysis Hydrosilylation Lewis acid Natural Products
eng
Doctor of Philosophy
Dissertation
University of North Carolina at Chapel Hill Graduate School
Degree granting institution
Michel
Gagne
Thesis advisor
Alexander
Miller
Thesis advisor
Maurice
Brookhart
Thesis advisor
Joseph
Templeton
Thesis advisor
Eric
Brustad
Thesis advisor
text
2017-05
Bender_unc_0153D_16931.pdf
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2017-04-27T13:48:56Z
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