College of Science and Health Theses and Dissertations

Date of Award

Summer 8-23-2013

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Chemistry

First Advisor

Justin Maresh, Ph.D.

Second Advisor

Caitlin Karver, Ph.D.

Third Advisor

Catherine A. Southern, Ph.D.

Abstract

There are several approaches to obtaining unnatural analogues of natural products. One of these approaches is precursor-directed biosynthesis (PDB), which is the process of using natural biosynthetic machinery to transform unnatural analogues of precursor compounds to produce an unnatural analogue of a target natural product. Berberine and galanthamine are chosen as model systems for the evaluation of PDB for the production of aromatic alkaloids in plants. Several approaches to the synthesis of unnatural 4 hydroxyphenylacetaldehyde (HPAA), norcoclaurine, and tyramine analogues are explored. 3-chloro-, 3-bromo-, and 3-iodoHPAA are all synthesized in good yields via and oxidative decarboxylation of tyrosine. These analogues are evaluated for use as unnatural precursors by monitoring their reaction rates with the enzyme norcoclaurine synthase. 3-chloro-,3-bromo-, and 3-iodonorcoclaurine are all synthesized in good yield from tyrosine using a one-pot biomimetic approach from tyrosine via an oxidative decarboxylation of tyrosine followed by a phosphate catalyzed Pictet-Spengler reaction between the HPAA analogue and dopamine. Additionally, the synthesis of 3-chloro- and 3-bromotyramine analogues from 4-hydroxybenzaldehyde is reported.

Included in

Chemistry Commons

Share

COinS