Aza-anthraquinones

Lithiation of 3,5-dibromopyridine with IDA and subsequent reaction with electrophiles provide 4-alkyl-3,5-dibromopyridines in high yield <96TL(37)2565>. The synthesis of aza-anthraquinones 39 via metallation of the pyridine ring of 38 was reported by Epsztajn <96T(52)11025>. 

Intramolecular oxidative coupling of silylated phenols 251 with IBTA leads to the formation of spiropiperidine derivatives 253, called aza-anthraquinone-spirodienones (89TL1119) (Scheme 64). The first step of this conversion is the electrophilic attack of reagent on the phenolic group to give intermediate 252. Intramolecular C—C bond formation leads... 

Direct formation of aza-anthraquinones 181 has been achieved using in situ generated lithio cyanophthalide 177 (a 1,4-dipole equivalent) and 3,4-pyridyne 178 (Scheme 52) [88H(27)2643]. Thus, addition of 3-bromopyridine derivative to a solution of LDA and 177 at -40°C leads, when warmed to room temperature, to aza-anthraquinones 181 in good yields via intermediates 179 and 180. This type of reaction has also been applied to 4-bromoquinoline to give benzo[rf]-2-azaanthraquinone in 60% yield [88H(27)2643]. 

An alternative focus based on known antitumor activity of adriamycin-type systems stimulated the synthesis of the aza-anthraquinones 599 and 600 (Scheme 177) (84CC897). Thus, synergistic chloro-oxazoline directed metalation of 597 with methyllithium followed by treatment with 2,5-dimethoxybenzaldehyde and acid-promoted cyclization provided the lactone 598. Radical bromination and base-induced hydrolysis gave an intermediate keto acid which, upon Friedel-Crafts cyclization with methanesulfonic acid, led to the aza-anthraquinone 599 in modest yield. The azanaphthacene dione 600 was prepared by an analogous series of reactions starting with 597. 

Alkaloids that possess quinolinequinone and quinolinequinoneimine units (1) have been classified in the literature as members of the aza-anthraquinone, diaza-anthraquinone, quinolinequinone, pyridoacridine, and pyrroloquinolinequinoneimine type alkaloids, although they all have common subunits (1), quinolinequinone and quinolinequinoneimine. Most of the alkaloids isolated in recent years with such units fall into the pyrido-... 

Oxidative cleavage of ring A of the catechol 476 would eventually give the aza-anthraquinone acid 477. Transformation of 477 would lead to 478, in which ring closure to a pyridone 479 would be followed by deoxygenation to form the intermediate sampangine (448). 

The relative and absolute configurations of diepoxydicarbazoles involving the 2,6-dioxa-4,8-diazaadamantane system were determined in the course of a study on indole and indole alkaloids.242 Water-soluble azo, anthraquinone, and phthalocyanine dyes which are substituted by a 4-chloro-s-triazin-2-ylamino group can be quaternized with a l-aza-3-methyl-4,6,10-trioxa-adamantane unit in aqueous medium at 40 50"C.243 Dyes mixed with... 

The same framework is contained in enaminone 256, which is the product of an aza-Diels-Alder reaction of morphanthridine 255 (made in five steps from anthraquinone) and Danishefsky s diene (07WO25938). 

A method for synthesis of anthraquinones is by reaction of cyanophthalide carban-ions with benzynes [162], It is particularly useful for the access of 2 aza-l,3,8-trimeth-oxyanthraquinone because of the high regioselectivity imposed by the methoxy groups and the nitrogen atom of the pyridine. 

A large number of quinones of the general structure 7 are known, where X corresponds to a heterocyclic residue containing one or more rings, and the chemistry of these has been reviewed extensively [6-8], If X consists of a benzenoid or aza-benzenoid ring system, then such compounds are best regarded as anthraquinone analogues. In the case of other heterocyclic residues, they may be considered as 1,4-naphthoquinone derivatives. 

In synthetic work towards tetracyclines the tricyclic dienone (99) was rearranged at 0 °C using boron trifluoride, to the anthraquinone (100 65%) apparently by a direct 1,5-shift. The quinamine (101) undergoes facile reorganization in hydrochloric acid to the biaryl (102) jn an aza-Claisen-like process. 

Hydroxy-1 -methoxy-2-(methoxymethy 1) anthraquinone, in D-10180 7-Hydroxy-2-methoxy-1 -methy l-4-aza-9-fluorenone, in D-30200 7-Hydroxy-5-methoxy-6-(3-methylbutanoyl) chromene, in D-30152... 

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