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Tripartite Prodrugs of the Anthracycline Anticancer Drug Candidate Doxazolidine: New Methods and Mechanisms Relevant to Their Synthesis
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| 자료유형 | 학위논문 |
|---|---|
| 서명/저자사항 | Tripartite Prodrugs of the Anthracycline Anticancer Drug Candidate Doxazolidine: New Methods and Mechanisms Relevant to Their Synthesis. |
| 개인저자 | Kirby, Thomas Price. |
| 단체저자명 | University of Colorado at Boulder. Chemistry. |
| 발행사항 | [S.l.]: University of Colorado at Boulder., 2019. |
| 발행사항 | Ann Arbor: ProQuest Dissertations & Theses, 2019. |
| 형태사항 | 241 p. |
| 기본자료 저록 | Dissertations Abstracts International 81-04B. Dissertation Abstract International |
| ISBN | 9781088328446 |
| 학위논문주기 | Thesis (Ph.D.)--University of Colorado at Boulder, 2019. |
| 일반주기 |
Source: Dissertations Abstracts International, Volume: 81-04, Section: B.
Advisor: Koch, Tad H. |
| 이용제한사항 | This item must not be sold to any third party vendors. |
| 요약 | This dissertation describes the development of a new method for the synthesis of tripartite prodrugs of the anticancer drug candidate doxazolidine, which utilizes, as the key transformation, the traceless Staudinger ligation (TSL) of an aryl azide. The rationale for developing a new synthetic methodology is presented in juxtaposition to the limitations of thepreexisting route for preparation of prodrugs containing the Katzenellebogan-spacer and this discussion focuses on improving the efficiency with which the chemical space surrounding such target molecules may be explored. A critical limitation to the newly developed method, namely, the inability to stereoselectively esterify C-chiral peptides with 2-(diphenylphosphino)phenol, which ultimately affords a mixture of diastereomeric products and, thereby, complicates the structural characterization and biological evaluation of the prepared prodrugs, is also discussed along with possible solutions to the problem. Mechanistic studies provide evidence that the TSL of an aryl azide proceeds via acyl-transfer to a phosphazide intermediate, as opposed to the iminophosphorane intermediate invoked in the putative mechanism of the TSL of an alkyl azide, in a reaction that depends on the concentration of water present in the reaction medium at the outset of the reaction. A revised mechanism for the TSL of an aryl azide and phosphino phenyl ester is ultimately presented alongside kinetic analysis of the reaction run under consecutive pseudo-first-order conditions in the presence of an excess of azide and water. |
| 일반주제명 | Chemistry. Organic chemistry. Physical chemistry. |
| 언어 | 영어 |
| 바로가기 | 
: 이 자료의 원문은 한국교육학술정보원에서 제공합니다. |
