Our goal is to develop an alternative chromophore to that present in azinomycin B for the purpose of identifying major groove binding small molecules. Through use of commercially available 1,3-dihydroxynapthalene as starting material, we are able to circumvent the synthesis of the 3-methoxy-5-methylnaphthalene unit of azinomycin B. The 3-hydroxyl is regioselectively methylated before introducing an allyl group on the 1-hydroxyl group, which is then transformed into the corresponding carboxylic acid by a three-step process involving oxidative cleavage, reduction, and oxidation. Dimerization of the carboxylic acid with a diamine linker and amide reduction then provides the target ligands, which will be tested for major groove binding by biophysical studies involving use of fluorescence intercalator displacement assays, circular dichroism, and ultraviolet spectroscopy. Small organic molecules exhibiting selectivity for the major groove hold promise of regulating gene expression through modulating the association of transcription factors with their cognate DNA binding sites.

Synthesis of dimeric naphthalene derivatives for recognition of DNA

255th National Meeting (2018)

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