Phenazines 1-hydroxy- from

Phenazines — These are dibenzopyrazine derivatives with fnnctional groups (hydroxy-, carboxy-) at C, and Cg and an oxygen or methyl gronp at Nj and N,o. There are also more complex structures, substituted phenazines, terpenoidal, and carbohydrate-containing phenazines and phenazines derived from saphenic acid. ... 

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... 

Ring substituents show enhanced reactivity towards nucleophilic substitution, relative to the unoxidized systems, with substituents a to the fV-oxide showing greater reactivity than those in the /3-position. In the case of quinoxalines and phenazines the degree of labilization of a given substituent is dependent on whether the intermediate addition complex is stabilized by mesomeric interactions and this is easily predicted from valence bond considerations. 2-Chloropyrazine 1-oxide is readily converted into 2-hydroxypyrazine 1-oxide (l-hydroxy-2(l//)-pyrazinone) (55) on treatment with dilute aqueous sodium hydroxide (63G339), whereas both 2,3-dichloropyrazine and 3-chloropyrazine 1-oxide are stable under these conditions. This reaction is of particular importance in the preparation of pyrazine-based hydroxamic acids which have antibiotic properties. 

On the other hand, there is at least one case of an aromatic amine without a hydroxy group in the 2-position, namely 1-aminophenazine (25) which, after the initial diazotiza-tion, is oxidized within minutes by air or additional nitrous acid to the quinone diazide 26 (equation 9)46. In the corresponding diazotization of 2-aminophenazine the proportion of the quinone diazide (isomer of 26) amounted to only 16%, but 30% unsubstituted phenazine was also found. The phenazine may have resulted from the overall redox reaction. 

Phenazines can be obtained from o-nitrodiphenylamines by reduction or from o-aminodiphenyla-mines by oxidative techniques. The preferred method is that of phenazine 9,10-dioxides from benzofuran, thus benzofuroxans, itself with hydroquinone, gives the 2-hydroxy derivative (Scheme... 

In the mass spectrum of phenazine an intense molecular ion at w/z 180 with significant contributions from the doubly charged molecular ion is observed fragmentations by loss of CN, HCN and C Hj (M-27) are characteristic. The mass spectrum of phenazine and isomeric hydroxy- and methoxyphenazine-1-carboxylic acids have been investigated in detail. Phenazine A -oxide shows an M O ion together with an intense M—CjHj ion and M-CO ion (w/z 168). ... 

Several phenazine derivatives, e.g. phenazin-2-ol, phenazine-l-carboxylic acid, 2-hydroxy-phenazine-1-carboxylic acid, phenazine-2,3-diol, and 2,3-dihydroxyphenazine-l-carboxylic acid have been isolated from Pseudomonas aureofaciens. 

Trimethoxyphenanthrene-9 10-quinone [lxxi] has not been prepared. The chromic acid oxidation of 3 4 6-trimethoxyphenan-threne gives instead 3 6-dimethoxyphenanthrene-l 4-quinone, clearly identified as [Lxxn] by its production in the same way from thebaol [lxvii, R = H]. This quinone condenses with o-phenylenediamine only with difficulty, losing a methoxyl group and giving 2-hydroxy-3 4 -(7 -methoxynaphtho-l 2 )-phenazine [lxxiii], whioh is soluble in... 

It follows from the above evidence that one of the hydroxy-groups in iodinin (180) is present before formation of the phenazine ring system. Accordingly, a highly efficient incorporation of 6-hydroxy-[7,9- H2]phenazine-l-carboxylic acid (as 179) into iodinin (180) was found. It thus appears probable that B. iodinum converts (170) and (179) by the same or similar enzyme systems into (178) and iodinin (180), respectively, N-oxide formation occurring either before or after hydroxylative decarboxylation. The two acids, (170) and (179), may well arise from the same (non-aromatic) precursor, by alternative aromatization reactions. 

Dihydroxyphenazine-l,6-dicarboxylic acid (157) has been isolated as its dimethyl ester from Pseudomonas cepacia Although the acid (157) has been proposed as an intermediate in phenazine biosynthesis before phenazine-1,6-dicarboxylic acid (152), the necessary loss in vivo of two phenolic hydroxy-groups in the formation of (152) or, e.g., (153), makes this highly unlikely, and preliminary testing " of the hypothesis supports this view. The dihydroxy-acid (157) could, however, be an intermediate, and more reasonably so, in the biosynthesis of compounds like lomofungin (155) at a stage after (152). 

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