Chemoenzymatic Formal Total Syntheses of Tetrodotoxin and an Approach to Daphenylline

This thesis describes chemoenzymatic formal total syntheses of tetrodotoxin and a concise synthetic approach to daphenylline. Advanced intermediates for the syntheses of tetrodotoxin reported by the groups of Fukuyama, Alonso, and Sato were prepared. Key steps included toluene dioxygenase-mediated dihydroxylation of either iodobenzene or benzyl acetate and a [4+2] hetero-Diels-Alder cycloaddition/Kornblum–DeLaMare rearrangement sequence to construct a common enone intermediate. The resulting key enone was transformed into Fukuyama's intermediate in four steps, into Alonso's intermediate in six steps, and into Sato's intermediate in seven steps. Fukuyama’s route employed a highly stereoselective allyl cyanate-to-isocyanate rearrangement to install the nitrogen atom at C8a. This protocol was also successfully applied in designing a synthetic avenue to daphenylline. The ABC tricyclic skeleton of daphenylline was successfully constructed in just eight steps starting from readily available (S)-carvone.

Name thesis:degree_name

Ph.D. Chemistry

Level thesis:degree_level

Doctoral

Discipline thesis:degree_discipline

Faculty of Mathematics and Science

Department dc:contributor.department

Department of Chemistry

Grantor

Brock University

Year dc:date.issued

2020

Author dc:creator

• Baidilov, Daler

• tetrodotoxin
• daphenylline
• total synthesis

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/10464/14612

OAI identifier oai:identifier

oai:brocku.scholaris.ca:10464/14612