Synthesis and Reactivity of New Organoboron Reagents and Development of New Methodologies for the Generation of Novel Drug-Like Scaffolds

Persistent Link:
http://hdl.handle.net/10150/265557
Title:
Synthesis and Reactivity of New Organoboron Reagents and Development of New Methodologies for the Generation of Novel Drug-Like Scaffolds
Author:
Bell, Christan Elizabeth
Issue Date:
2012
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Embargo:
Release after 20-Dec-2013
Abstract:
This research focused on the synthesis of novel ogranoboron reagents in efforts to perform a variety of synthetic transformations, and additionally, the development of new methodologies to generate drug-like scaffolds. Initially, three novel tripod ligands were synthesized, and two were effectively chelated to boron to provide the desired organoborates. Such organoborates were employed in nucleophilic additions where they were found to be ineffective, whereas some activity was observed in Suzuki-Miyaura cross-coupling reactions. An additional project on organoboron compounds was conducted and focused on the development of organoboron frustrated Lewis pairs (FLPs) to facilitate the storage and transfer of hydrogen, nucleophilic addition reactions, and Claisen rearrangements. A new method for synthesizing a pyrrolidine diol unit was accomplished, and this intermediate was utilized to synthesize two FLPs. The reactivity of the FLPs with small molecules was assessed, and the pyrrolidine diol unit was subsequently evaluated for its ability to undergo a multicomponent reaction (MCR) to yield compounds possessing beneficial biological activity. Further research in this area was conducted, and a 5-aminoimidazole scaffold was synthesized employing a new MCR which is more efficient than previously reported methodologies. 5-Aminoimidazoles are frequently found in compounds which possess desirable biological activity, and this novel method was employed to generate a library of eleven 5-aminoimidazoles. Additionally, two post condensation modification reactions were developed. During initial studies, a side product was observed which was identified as a dihydrotriazine, which is another biologically appealing chemotype. Therefore, an enhanced method of synthesizing this product was developed, and a library of eleven dihydrotriazines was produced. In summary, novel organoboron reagents were synthesized, and their activity was evaluated. The pyrrolidine diol utilized to synthesize FLPs was applied towards an MCR. Furthermore, a novel MCR was developed for the synthesis of 5-aminoimidazoles, and an enhanced protocol for the synthesis of dihydrotriazines was found.
Type:
text; Electronic Dissertation
Keywords:
multicomponent reaction; Chemistry; cross-coupling; Frustrated Lewis pairs
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Graduate College; Chemistry
Degree Grantor:
University of Arizona
Advisor:
Hulme, Christopher

Full metadata record

DC FieldValue Language
dc.language.isoenen_US
dc.titleSynthesis and Reactivity of New Organoboron Reagents and Development of New Methodologies for the Generation of Novel Drug-Like Scaffoldsen_US
dc.creatorBell, Christan Elizabethen_US
dc.contributor.authorBell, Christan Elizabethen_US
dc.date.issued2012-
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.releaseRelease after 20-Dec-2013en_US
dc.description.abstractThis research focused on the synthesis of novel ogranoboron reagents in efforts to perform a variety of synthetic transformations, and additionally, the development of new methodologies to generate drug-like scaffolds. Initially, three novel tripod ligands were synthesized, and two were effectively chelated to boron to provide the desired organoborates. Such organoborates were employed in nucleophilic additions where they were found to be ineffective, whereas some activity was observed in Suzuki-Miyaura cross-coupling reactions. An additional project on organoboron compounds was conducted and focused on the development of organoboron frustrated Lewis pairs (FLPs) to facilitate the storage and transfer of hydrogen, nucleophilic addition reactions, and Claisen rearrangements. A new method for synthesizing a pyrrolidine diol unit was accomplished, and this intermediate was utilized to synthesize two FLPs. The reactivity of the FLPs with small molecules was assessed, and the pyrrolidine diol unit was subsequently evaluated for its ability to undergo a multicomponent reaction (MCR) to yield compounds possessing beneficial biological activity. Further research in this area was conducted, and a 5-aminoimidazole scaffold was synthesized employing a new MCR which is more efficient than previously reported methodologies. 5-Aminoimidazoles are frequently found in compounds which possess desirable biological activity, and this novel method was employed to generate a library of eleven 5-aminoimidazoles. Additionally, two post condensation modification reactions were developed. During initial studies, a side product was observed which was identified as a dihydrotriazine, which is another biologically appealing chemotype. Therefore, an enhanced method of synthesizing this product was developed, and a library of eleven dihydrotriazines was produced. In summary, novel organoboron reagents were synthesized, and their activity was evaluated. The pyrrolidine diol utilized to synthesize FLPs was applied towards an MCR. Furthermore, a novel MCR was developed for the synthesis of 5-aminoimidazoles, and an enhanced protocol for the synthesis of dihydrotriazines was found.en_US
dc.typetexten_US
dc.typeElectronic Dissertationen_US
dc.subjectmulticomponent reactionen_US
dc.subjectChemistryen_US
dc.subjectcross-couplingen_US
dc.subjectFrustrated Lewis pairsen_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.disciplineChemistryen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorHulme, Christopheren_US
dc.contributor.committeememberChristie, Hamish S.en_US
dc.contributor.committeememberPolt, Robin L.en_US
dc.contributor.committeememberPyun, Jefferyen_US
dc.contributor.committeememberWalker, F. Annen_US
dc.contributor.committeememberLichtenberger, Dennis L.en_US
dc.contributor.committeememberHulme, Christopheren_US
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