Enabling Chemistry to Expedite the Delivery of Pharmacologically Relevant Small Molecules

Persistent Link:
http://hdl.handle.net/10150/265595
Title:
Enabling Chemistry to Expedite the Delivery of Pharmacologically Relevant Small Molecules
Author:
Gunawan, Steven
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:
Dissertation Not Available (per Author's Request)
Abstract:
Operationally friendly protocols to produce libraries of novel small molecules with high molecular complexity are in huge demand for the interrogation of biological systems. As such, development of new MCRs and post-condensation modification of the MCR products have proven fruitful in the quest for new molecular probes and their expedited progression along the drug discovery value chain. The products thereof have found their way into numerous corporate compound collections. Crixivan (Indinavir), an antiretroviral, and Xylocaine (Lidocaine), a local anesthetic, are two examples of drugs derived from an MCR that have been marketed. The research topic of this dissertation encompasses the design and development of fifteen novel drug-like chemotypes in an operationally friendly, green, and expedited (≤ 3 synthetic operations) manner involving the Ugi MCR coupled with MAOS and high-throughput purification platforms. Over 500 drug-like small molecules (purity > 90% based on UV 214 nm and ELSD) have been synthesized, purified, and submitted to the NIH MLSMR for further biological evaluation against protein targets of interest. Furthermore, non-electrochemical carbamate oxidations enabling formation of N-acyliminium ion precursors, which are reactive intermediates that form the basis of a multitude of synthetic routes to natural products, have also been developed.
Type:
text; Electronic Dissertation
Keywords:
N-acyliminium; Radical bromination; Tetrazole; Ugi reaction; Chemistry; Molecular diversity; Multi-component reaction
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.titleEnabling Chemistry to Expedite the Delivery of Pharmacologically Relevant Small Moleculesen_US
dc.creatorGunawan, Stevenen_US
dc.contributor.authorGunawan, Stevenen_US
dc.date.issued2012en
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.releaseDissertation Not Available (per Author's Request)en_US
dc.description.abstractOperationally friendly protocols to produce libraries of novel small molecules with high molecular complexity are in huge demand for the interrogation of biological systems. As such, development of new MCRs and post-condensation modification of the MCR products have proven fruitful in the quest for new molecular probes and their expedited progression along the drug discovery value chain. The products thereof have found their way into numerous corporate compound collections. Crixivan (Indinavir), an antiretroviral, and Xylocaine (Lidocaine), a local anesthetic, are two examples of drugs derived from an MCR that have been marketed. The research topic of this dissertation encompasses the design and development of fifteen novel drug-like chemotypes in an operationally friendly, green, and expedited (≤ 3 synthetic operations) manner involving the Ugi MCR coupled with MAOS and high-throughput purification platforms. Over 500 drug-like small molecules (purity > 90% based on UV 214 nm and ELSD) have been synthesized, purified, and submitted to the NIH MLSMR for further biological evaluation against protein targets of interest. Furthermore, non-electrochemical carbamate oxidations enabling formation of N-acyliminium ion precursors, which are reactive intermediates that form the basis of a multitude of synthetic routes to natural products, have also been developed.en_US
dc.typetexten_US
dc.typeElectronic Dissertationen_US
dc.subjectN-acyliminiumen_US
dc.subjectRadical brominationen_US
dc.subjectTetrazoleen_US
dc.subjectUgi reactionen_US
dc.subjectChemistryen_US
dc.subjectMolecular diversityen_US
dc.subjectMulti-component reactionen_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, Hamishen_US
dc.contributor.committeememberHurley, Laurenceen_US
dc.contributor.committeememberWondrak, Georgen_US
dc.contributor.committeememberHulme, Christopheren_US
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