Microwave-assisted solid-phase reactions of Dotz benzannulation of naphthoquinones and "click chemistry" of azide-acetylene cycloaddition-efficient formation of water disperse micelles
Solid-phase organic chemistry offers an efficient route to construct large libraries of lead compounds for combinatorial chemistry. 2,3-disubstituted naphthoquinone derivatives exhibit a broad spectrum of biological activities that may be attenuated by the incorporation of protein recognition elements, amphiphilic properties and active groups for future incorporation of bioactive compounds. The Dötz benzannulation is a powerful method to construct naphthoquinones that could easily incorporate of the properties mentioned above. ^ The required disubstituted alkynes precursors have been prepared by the palladium-catalyzed Sonogashira coupling of mono or di-protected propargylamine with iodo alkyl benzoates in good to excellent yields. The microwave-assisted Dötz benzannulation of the resultant alkynes with solid supported phenyl Fischer chromium carbene complex and subsequent cleavage of the beads afforded (3-aminomethyl-2-benzoyl alkyl ester)-1,4-naphthoquinones in moderate to good yields. The presence of an amino group and a carboxyl group in the 1,4-naphthoquinone moiety could be an ideal candidate for the incorporation of polypeptides. ^ Click Chemistry ([3+2] cycloaddition) of azides and acetylenes has been extremely used in organic chemistry due to its practical and reliability. (Abstract shortened by UMI.)^
Bugarin Cervantes, Alejandro, "Microwave-assisted solid-phase reactions of Dotz benzannulation of naphthoquinones and "click chemistry" of azide-acetylene cycloaddition-efficient formation of water disperse micelles" (2006). ETD Collection for University of Texas, El Paso. AAI1436395.