Title

The Nucleophilic Substitution Reaction of 2-Bromo-3-methoxy-1,4-naphthaquinone with Amino Acid Residues

Authors

Heather Crump

Document Type

Article

Publication Date

2004

Abstract

Biologically active quinones benefit various aspects of medicine including anticancer and antibacterials. Through the derivation of 1,4-naphthoquinone with an amino acid residue and/or a peptide, we hope to enhance the medicinal value of 1,4-naphthoquinones, thereby facilitating the delivery of a 1,4-naphthoquinone derivative to specified locations in vivo . When exploring the reactivity of 2-bromo-3-methoxy-1,4-naphthoquinone with L -lysine ethyl ester dihydrochloride and L -cysteine ethyl ester hydrochloride, we find that the reactivity of the 2- and 3- positions of 2-bromo-3-methoxy-1,4-naphthaquinone depends on the reaction conditions. Triethylamine is added to deprotonate the ammonium salt to free amino acid. When one equivalent of triethylamine is added to a equimolar mixture of L -lysine ethyl ester dihydrochloride and quinone, a ?one-to-one? product, 2-bromo-3-(5-amino-5-ethoxycarbonylpentylamino)-1,4-naphthoquinone, is formed as a result of the substitution of the 3-methoxy group with the e-amino group of L -lysine ethyl ester. In the presence of two equivalents of triethylamine, both the a-amino group and the e-amino group of L -lysine ethyl ester are reacted with two quinone molecules, forming a ?one-to-two? product, N,N?-[bis(2-bromo-1,4-naphthaquinonyl)]lysine ethyl ester. Using a tandem substitution process, the ?one-to-one? product further reacts with L -cysteine ethyl ester, in which a thiolate anion replaces the bromine at the 2-position of the quinone residue, providing a disubstituted product, 2-(2-amino-2-ethoxycarbonylethylthio)-3-(5-amino-5-ethoxycarbonylpentylamino) -1,4-naphthoquinone. Further studies using peptide chains will help further tune the biological activity of a 1,4-naphthaquinone.

Advisor

T. Otsuki

Department

chem

Support

Support provided by:Sherman-Fairchild Foundation Grant Fellowship

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