Enantiodivergent chemoenzymatic synthesis of codeine

The present thesis describes our latest results in the chemistry of morphine alkaloids. An enantiodivergent synthesis of codeine utilizing a cis-cyclohexadiene diol derived from microbial whole cell oxidation of ~-bromoethylbenzene,as starting material is discussed. The total synthesis of (+)-codeine in 14 steps featuring a Mitsunobu inversion and two intramolecular Heck cyclizations is presented. Investigation of a regioselective nucleophilic opening of a homochiral vinyl oxirane, which led to a total synthesis of the natural isomer of codeine, is detailed. Furthermore, described herein are novel methodologies designed for the transformation of naturally occurring opiates into medicinally relevant derivatives. Two studies on the conversion of thebaine into the commercially available analgesic hydrocodone, two novel ·transition metal catalyzed N-demethylation procedures for opioids, and the development of a catalytic protocol for N-demethylation and Nacylation of morphine and tropane alkaloids are presented. In addition, reactions of a menthol-based version of the Burgess reagent with epoxides are discussed. The synthetic utility of this novel chiral derivative of the Burgess reagent was demonstrated by an enantiodivergent formal total synthesis of balanol. ii

Name thesis:degree_name

Ph.D. Biotechnology

Level thesis:degree_level

Doctoral

Discipline thesis:degree_discipline

Faculty of Mathematics and Science

Department dc:contributor.department

Centre for Biotechnology

Grantor

Brock University

Year dc:date.issued

2009

Author dc:creator

• Leisch, Hannes G.

• Codeine--Synthesis.

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/10464/1444

OAI identifier oai:identifier

oai:brocku.scholaris.ca:10464/1444