Date of Award
Doctor of Philosophy (PhD)
Mark L. McLaughlin
Constrained amino acids and benzannulated analogs of indole were synthesized as potential fluorescence probes of peptide structure. 1-Amino-2-(3-indolyl)-cyclohexane-1-carboxylic acid (W3) is a rotationally-restricted tryptophan analog whose C$\sb\alpha$-C$\sb\beta$ bond is part of a 6-membered ring. Friedel-Crafts reaction between $\alpha$-hydroxycyclohexanone and indole affords 2-(3-indolyl)cyclohexanone which is further converted into its corresponding spirohydantoin derivative via Strecker reaction. Basic hydrolysis of this hydantoin derivative with Ba(OH)$\sb2$ in oxygen-free water at 250$\sp\circ$C in a Parr$\sp\circler$ high pressure bomb afforded the constrained tryptophan analog. N-(t-Boc)piperidine-4-amino-4-carboxylic acid is a constrained Aib analog. Treatment of 4-piperidinone monohydrate hydrochloide with triethyl amine, catalytic amounts of N,N-dimethylamino pyridine and di-tert-butyl dicarbonate affords N-(t-Boc)-4-piperidinone which is transformed into its corresponding spirohydantoin derivative via Strecker reaction. This hydantoin derivative is fully reacted with di-tert-butyl dicarbonate and hydrolyzed with aq. 1N LiOH in THF to provide the desired a-amino acid product. Benz (f) indole is synthesized via Batcho-Leimbruger reaction between 3-methyl-2-nitronaphthalene and a mixture of pyrrolidine/N,N-dimethylformamide dimethyl acetal followed by hydrogenation at 30 p.s.i. 3-Methyl-benz (f) indole is synthesized via palladium-catalyzed cyclization reaction between 3-bromo-2-aminonaphthalene and 1-trimethylsilyl-propyne in refluxing acetonitrile followed by reflux with HC1. Progress towards the synthesis of benz (f) tryptophan using 3-bromo-2-aminonaphthalene and several terminal-silated alkyne derivatives via palladium-catalyzed cyclization reactions is also reported.
Morales, Guillermo, "Synthesis of Benz(f)tryptophan and Constrained Amino Acid Derivatives as Fluorescence Probes." (1995). LSU Historical Dissertations and Theses. 6037.