Simple Phenazines

Phenazines — This large class of compounds includes more than 6,000 natural and synthetic representatives. Natural phenazines are secondary metabolites of certain soil and marine microorganisms. The main phenazine producers are Pseudomonas and Streptomyces species. Pseudomonas strains produce the most simple phenazines tubermycin B (phenazine-1-carboxylic acid), chlororaphine, pyocyanin, and iodinine. Pyocyanin is a blue pigment while chlororaphine is green both are produced by Pseudomonas aeruginosa. They can be seen in infected wounds of animal and human skins. Iodinine is a purple phenazine produced by Pseudomonas aureofaciens. 

Table 1. Simple Phenazine Compounds Produced by Pseudomonas sp ...

Several of the simple phenazines described above are also produced by the Gram-positive actinomycete, Streptomyces (e.g., Ih, 3, and 6), but in the following... 

The ease of oxidation varies considerably with the nature and number of ring substituents thus, although simple alkyl derivatives of pyrazine, quinoxaline and phenazine are easily oxidized by peracetic acid generated in situ from hydrogen peroxide and acetic acid, some difficulties are encountered. With unsymmetrical substrates there is inevitably the selectivity problem. Thus, methylpyrazine on oxidation with peracetic acid yields mixtures of the 1-and 4-oxides (42) and (43) (59YZ1275). In favourable circumstances, such product mixtures may be separated by fractional crystallization. Simple alkyl derivatives of quinoxalines are... 

Second only to sulfur-based systems, nitrogen complexes are relatively well represented in the structural literature with 41 complexes reported. Of these, 25 are with I2 as the electron acceptor, 11 are with the interhalogen IC1, three are with Br2, and two are with IBr. As expected, in every case the halogen bond forms between the nitrogen and the softest halogen atom, i.e., iodine, in all of the complexes except those with dibromine. Most N I2 complexes, and all N Br2, N IBr, and N IC1 complexes are simple adducts, mode A. Exceptions for the diiodine complexes include bridging mode (B) observed for diazines, such as pyrazine [86], tetramethylpyrazine [86], phenazine, and quinoxaline [87], and for 9-chloroacridine [89] and the 1 1 complex of diiodine with hexamethylenetetramine [144] and amphoteric bridging mode (BA) observed for 2,2 -bipyridine [85], acridine [89], 9-chloroacridine [89], and 2,3,5,6-tetra-2/-pyridylpyrazine [91]. The occurrence of both B and BA complexes with 9-chloroacridine, and of B and A complexes and an... 

Irradiation of phenazine (2, > 330 nm) in the presence of simple aliphatic aldehydes gives (V-acylated 5,10-dihydrophenazines, e.g. with acetaldehyde, 5-acetyl-5,10-dihydrophenazine is formed in 35% yield. 

The parent heterocycle and methyl- and methoxy-substituted derivatives have been obtained in low yields by reactions of anilinonitro-pyridines with ferrous oxalate at 260-280°. This extension of a conventional phenazine synthesis is the only reported approach to simple examples of this ring system. ... 

Availability of nitroarenes and anilines opens almost unlimited simple and efficient access to phenazines, as well as to their derivatives condensed with an additional ring, as exemplified by the synthesis of pyrrolo[3,2-h]phenazine from 5-nitroindoles (Scheme 99) [234]. 

Phenazines isolated from Pseudomonas strains (e.g., aeruginosa, aureofaciens, fluorescens, and cepacia) are mostly simple hydroxyl- and carboxyl-substituted structures (Table 1), often Q-symmetric,... 

Other noteworthy phenazines that resemble simple metabolites produced by Pseudomonas include the mono-oxide derivative (47) of iodinin isolated from Burkholderia phenaziniurrP and Waksmania aer-ata and the di-A/ oxide, myxin (l-hydroxy-6-meth-oxyphenazine-5,10-di-A/k)xide, 48 Figure 6), isolated from a Sorangium species. Myxin showed in vitro inhibition of DNA and RNA synthesis and reduction of the protein synthesis. It was shown that myxin (48) affected the rate terms for incorporation of GTP and GTP into RNA but not for incorporation of ATP and UTP by interaction with GG base pairs in an intercalation fashion. The first and so far only report on phenazines isolated from archaea was the recent isolation of methanophenazine (49) from the... 

G. H. Mahdavinia, M. Mirzazadeh, B. Notash, Tetrahedron Lett. 2013, 54, 3487-3492. A rapid and simple diversity-oriented synthesis of novel 3-amino-2 -oxospiro[benzo[c] pyrano[3,2-a]phenazine-1,3 -indoline] -2-carbonitrile/carbox-ylate derivatives via a one-pot, four-component domino reaction. 

Comparison of the electron-transfer efficiency provided by different mediators in the presence of the same redox enzyme allows the definition of the important parameters of MET. The reaction of glucose oxidase (GOx) has been extensively studied with a number of artificial electron acceptors including organic dyes such as phenazine methosul-fate, 2,6-dichlorophenolindophenol, and N, N, N, A -tetramethyl-4-phenylenedia-mine [26]. However, these mediators have a number of limitations such as poor stability and the pH dependence of their redox potentials. Simple inorganic redox species such as hexacyanofer-rate [27], hexacyanoruthenate, and pen-taamine pyridine ruthenium [28] do not suffer from these problems. These... 

This work was continued by Dickens, who also used a fraction from autolyzed yeast, TPN, and as the autoxidizable hydrogen carrier, phenazine or a flavoprotein system. Dickens isolated various products, one of which appeared to be a mucture of a phosphopentonic acid and a phosphoketohexonic acid, and others analyzed as 5- and 4-carbon phosphate esters. The 5-carbon compound gave a reaction in the Bial FeClj-orcinol test which was characteristic of pentose. In general, the enzyme preparations of this period did not yield simple reaction products, nor were the methods available for the separation and characterization of the small amounts of products which were isolated. For instance, although suggestions were obtained of the presence of pentose in the products, this was not unequivocally demonstrated. 

Oxidation of Breslow intermediates provides a means for unique a-functionalization of simple aldehydes. With phenazine as the oxidant and an NHC catalyst, Rovis group reported an oxidative coupling reaction of simple aldehydes with a,p-unsaturated ketones and imines to afford the corresponding disubstituted lactones and lactams in almost optically pure form (Scheme 7.18). Chi s group reported a similar reaction with a different oxidant, and the reaction mechanism is briefly discussed in the following section. ... 

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