자료유형  

 학위논문

Control Number  

0015492545

International Standard Book Number  

9781088328446

Dewey Decimal Classification Number  

541

Main Entry-Personal Name  

Kirby, Thomas Price.

Publication, Distribution, etc. (Imprint  

[Sl] : University of Colorado at Boulder, 2019

Publication, Distribution, etc. (Imprint  

Ann Arbor : ProQuest Dissertations & Theses, 2019

Physical Description  

241 p

General Note  

Source: Dissertations Abstracts International, Volume: 81-04, Section: B.

General Note  

Advisor: Koch, Tad H.

Dissertation Note  

Thesis (Ph.D.)--University of Colorado at Boulder, 2019.

Restrictions on Access Note  

This item must not be sold to any third party vendors.

Summary, Etc.  

요약This 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.

Subject Added Entry-Topical Term  

Chemistry

Subject Added Entry-Topical Term  

Organic chemistry

Subject Added Entry-Topical Term  

Physical chemistry

Added Entry-Corporate Name  

University of Colorado at Boulder Chemistry

Host Item Entry  

Dissertations Abstracts International. 81-04B.

Host Item Entry  

Dissertation Abstract International

Electronic Location and Access  

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Control Number  

joongbu:565153