|dc.description.abstract||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