87614-40-2

Usage

InChI:InChI=1/C20H22N2O4/c1-5-7-11-9(3)19(25)21-15-13(11)17(23)14-12(8-6-2)10(4)20(26)22-16(14)18(15)24/h5-8H2,1-4H3,(H,21,25)(H,22,26)

Upstream product

• 120040-68-8 N,N'-(2,5-dihydroxy-1,3-phenylene)bis(2-methyl-3-oxohexanamide) 
• 19643-45-9 2,6-dibromo-1,4-benzoquinone 
• 64299-58-7 (E)-2-methyl-2-hexenal 
• 88939-15-5 S-tert-butyl-3-oxohexanethioate 
• 120063-31-2 N,N'-[2,5-bis(methoxymethoxy)-1,3-phenylene]bis(2-methyl-3-oxohexanamide) 
• 120040-74-6 2,5-bis(methoxymethoxy)-1,3-dinitrobenzene 
• 120063-30-1 2,5-bis(methoxymethoxy)benzene-1,3-diamine 
• 13985-45-0 2,6-dinitrohydroquinone 
• 120040-67-7 methyl 2-methyl-3-oxohexanoate 
• 288613-87-6 3,7-dimethyl-1-oxy-4,6-dipropyl-pyrido[3,2-g]quinoline-5,10-dione 
• 288613-86-5 3-methyl-4-propyl-5,8-dimethoxy-2(1H)-quinolinone 
• 288613-85-4 N-(2,5-dimethoxyphenyl)-2-methyl-3-oxohexanamide 
• 288613-84-3 S-tert-butyl 2-methyl-3-oxothiohexanoate 
• 288613-92-3 2-methyl-2-hexenal dimethylhydrazone 

Downstream Products

• 87614-43-5 2,8-Dimethoxy-3,7-dimethyl-4,6-dipropyl-pyrido[3,2-g]quinoline-5,10-dione 

Relevant academic research and scientific papers

Total synthesis of diazaquinomycin A

Two concise total syntheses of the diazaanthraquinone antibiotic diazaquinomycin A are reported. The first route features a double hetero Diels-Alder reaction between 2,6-dibromobenzoquinone and 2-methyl-2-hexenal dimethylhydrazone, aromatization by a novel, one-pot N-oxidation/elimination procedure with percarbamide in trifluoroacetic acid, and double N-oxidation followed by rearrangement to a double lactam system. The key step of the second route is a hetero Diels-Alder reaction between 2-methyl-2-hexenal dimethylhydrazone and 3-methyl-4-propyl-1H-quinoline-2,5,8-trione.

Scope and Optimization of the Double Knorr Cyclization: Synthesis of Novel Symmetrical and Unsymmetrical Tricyclic 1,8-Diazaanthraquinones

The Knorr cyclization of β-ketoanilides to form 2-quinolones in the presence of acid is well documented chemistry. Double Knorr cyclization is rare, with very few examples appearing in the literature to date. The double Knorr methodology can provide access to tricyclic 1,8-diazaanthraquinones, a scaffold seen in the diazaquinomycin family. The optimized synthesis of diazaquinomycin A and structural analogues thereof via double Knorr cyclization of di-β-ketoanilide precursor substrates is reported. The scope and generality of the double Knorr cyclization were investigated along with an optimization study. The double Knorr cyclization was found to be sensitive to steric bulk on precursor substrates. In addition, the presence of a 5-hydroxy group on the 1,3-di-β-ketoanilide facilitated the double Knorr cyclization, possibly due to its stabilizing effect on the carbocation intermediates formed during the reaction.

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- dihydropyridine moieties with the urea-hydrogen peroxide complex (UHP) led to their efficient aromatization. Double N-oxidation of 1,8-diazaanthraquinones thus obtained is the first example of a double N-oxidation of a diaza heterocycle by 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 alternative synthesis of diazaquinomycin A was also devised, whose key steps are the hetero Diels-Alder reaction between 2- methyl-2-hexenal dimethylhydrazone and 3-methyl-4-propyl-2H-quinoline-2,5,8- trione and the oxidative functionalization of the 1,8-diazaanthracene-2,9,10- trione derivative thus obtained. (C) 2000 Elsevier Science Ltd.

SYNTHESIS OF DIAZAQUINOMYCIN A AND B: THE FIRST DOUBLE KNORR CYCLIZATION

The first syntheses of diazaquinomycin A (1) and diazaquinomycin B (11) are described.The key reaction is the tandem double Knorr cyclization/oxidation of 10 to 1 (Eq. 1).

THE STRUCTURES OF DIAZAQUINOMYCINS A AND B, NEW ANTIBIOTIC METABOLITES

Novel substituted 1,8-diazaanthraquinone structures of diazaquinomycins A and B were determined by the application of nmr spectroscopy.