Date of Award
Doctor of Philosophy (PhD)
Mark L. McLaughlin
Benzannulated and a series of constrained derivatives of the essential amino acids tyrosine and tryptophan were synthesized. The synthesis of the two benzannulated tyrosine analogs followed traditional synthetic protocols that basically consisted of obtaining key oxazolones and further elaboration to the target amino acids; the latter compounds were obtained as racemic mixtures. All the reaction intermediates were fully characterized spectroscopically, and when possible, structure proof was established by X-ray crystallographic determinations. Asymmetric hydrogenation studies on the intermediate (Z)-2-benzoylaminoacrylic acids were undertaken in an effort to obtain enantiomerically pure materials. The products were, in fact, chiral upon hydrogenation in the presence of Rh(BINAP) catalyst. Evidence of chirality was established by the determination of the optical activity. NMR experiments with a europium chiral shift reagent indicated that in the case of the monosubstituted naphthalene derivatives, the hydrogenation afforded only one enantiomer. The ee of the disubstituted derivatives as well as the configuration of all major products remains to be determined. Two constrained derivatives of tyrosine where the alanyl side chain was incorporated into five- and six-membered rings were also prepared. The constrained derivatives of tryptophan were synthesized by means of the Pictet-Spengler reaction and the Fischer indolization process. Progress made towards the preparation of cyclopropane-tryptophan is reported. The latter compound contains a cyclopropane ring that prevents rotation about the $\alpha$-$\beta$ bonds of the alanyl side chain of the amino acid. All these derivatives will be tested as isomorphic replacements of the native amino acids. Their utility as intrinsic fluorescent probes will be scrutinized. Because of the minimal structural changes that the synthesized amino acids possess, they are expected to mimic the behavior of the original amino acids closely. The second part of this manuscript is a compilation of the methods used to introduce prenyl moieties onto flavonoid-type compounds.
Vela, Marco A., "The Synthesis of Constrained and Benzannulated Derivatives of the Essential Amino Acids Tyrosine and Tryptophan." (1989). LSU Historical Dissertations and Theses. 4889.