Date of Award

1995

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Chemistry

First Advisor

Mark L. McLaughlin

Abstract

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.

Pages

156

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