Concise preparation of 1,8-diazaanthracene-2,7,9,10-tetraones. Two alternative syntheses of the natural antifolate diazaquinomycin A

Treatment of compounds bearing one or two 1-dimethylamino-1,4-dihydropyridi ne moieties with the urea-hydrogen peroxide complex (UHP) led to their effi cient aromatization. Double N-oxidation of 1,8-diazaanthraquinones thus obt ained is the first example of a double N-oxidation of a diaza heterocycle b y UHP in trifluoroacetic acid. Treatment of the crude double N-oxides with tosyl chloride in acetonitrile-water afforded 1,8-diazaanthracene-2,7,9,10- tetraones (including diazaquinomycin A) in 25-40% overall yields. An altern ative synthesis of diazaquinomycin A was also devised, whose key steps are the hetero Diels-Alder reaction between 2-methyl-2-hexenal dimethylhydrazon e and 3-methyl-4-propyl-2H-quinoline-2,5,8-trione and the oxidative functio nalization of the 1,8-diazaanthracene-2,9,10-trione derivative thus obtaine d. (C) 2000 Elsevier Science Ltd. All rights reserved.