Synthesis of Bicyclic and Tricyclic Analogues of Oxazolidinone

<p>Oxazolidinones are known as a new class of antibacterial agents. In our group, the 4,5-disubstituted oxazolidinones have been previously identified to exhibit high affinity for the T box antiterminator transcription system. Among those compounds, ANB-22 and ANB-40 emerged to be the lead compounds showing good RNA-binding activity with high affinity and specificity. In medicinal chemistry, conformationally constraining molecules is a useful approach to optimize the biological activities of drug candidates. This dissertation is devoted to the design and synthesis of the fused tricyclic piperazine analogues and tricyclic triazole analogues of ANB-22 and ANB-40. </p><p>By employing the aziridine-ring-opening and the Mitsunobu reaction, a series of fused bicyclic and tricyclic oxazolidinone-piperazine derivatives have been prepared. Using similar synthetic strategy and subsequent structural modification, the fused tricyclic piperazine analogues of ANB-22/40 have been successfully obtained as well.</p><p>The application of the intramolecular azide-alkyne cycloaddition leads to the tricyclic fused oxazolidinone-piperazine-triazole compounds. After appropriate structural modification, the triazole analogues of ANB-22/40 have been prepared. By hydrolyzing the oxazolidinone ring of these tricyclic compounds, a series of amino alcohol derivatives with a piperazine-triazole framework have been generated. In addition, the use of copper catalyst allows the occurrence of the intermolecular cycloaddition to afford four macrocyclic dimers.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

doctoral

Discipline thesis:degree_discipline

Chemistry and Biochemistry (Arts and Sciences)

Grantor dc:publisher

Ohio University

Year dc:date

2013

Author dc:creator

• Fang, Fang

Contributors dc:contributor

• Bergmeier, Stephen
• Chen, Shawn

• Chemistry
• Oxazolidinone
• aziridine-ring-opening
• Mitsunobu reaction
• piperazine-triazole framework

Statement dc:rights

• unrestricted
• This thesis or dissertation is protected by copyright: some rights reserved. It is licensed for use under a Creative Commons license. Specific terms and permissions are available from this document's record in the OhioLINK ETD Center.

Language dc:language

English

Repository record dc:identifier

http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1357312054

OAI identifier oai:identifier

oai:etd.ohiolink.edu:ohiou1357312054