Synthesis of 7-Amino-6-methoxy-5, 8-quinolinequinone Derivatives.
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Streptonigrin, a derivative of 7-amino-6-methoxy-5,8-quinolinequinone, was first isolated from the bacterium Steptomyces flocculus forty years ago. It has proven to be a good substrate of NAD(P)H: quinone oxidoreductase, which is over expressed in tumors of the colon, breasts and lungs. It is suggested that the enzymatic process of NAD(P)H: quinone oxidoreductase with streptonigrin produces an hydroxy (OH) radical that induces the breakage of DNA strands and consequently, various cell toxins. Recently, a less complicated family of streptonigrin has proved to be a more effective substrate for the NAD(P)H: quinone oxidoreductase. The simplest member of this family, 6-methoxy-5,8-quinolinequinone, is prepared starting from the commercially available 6-hydroxyquinoline, via a four-step synthesis, namely the formation of methyl ether at the C6 position of the hydroxy group, nitration at the C5 position, reduction of the nitro group to an amine, and oxidation of the amine by Fremy's salt. Thus far, we have studied conditions through the second nitration step. Once the 6-methoxy-5,8-quinolinequinone is prepared, we plan to introduce various N substituents at this compound's C7 position producing a structure that better resembles that of streptonigrin's. We anticipate that this new family of aminoquinolinequinones will be an even better substrate for NAD(P)H: quinone oxidoreductase resulting in a more effective antitumor agent.