2-Hydroxyphenazine-l-carboxylic acid

Using ether-treated cells of P. aureofaciens, dicarbonyl-14C2 phenazme-l,6-dicarboxylic acid las (121)1 was found to be an efficient and specific precursor for phenazine-1-carboxylic acid (123), and also for 2-hydroxyphenazine-l-carboxylic acid (124). The rate of growth of the organism appeared to be important, because an incorporation was also recorded of the labelled (121) into (123), albeit at a lower level, with cultures that had been grown rapidly. The position of phenazine-1,6-dicarboxylic acid (121) as a universal intermediate in the biosynthesis of phenazines now seems secure. The previously reported failure of dimethyl phenazine-1,6-dicarboxylate (122) to act as a precursor of phenazines cf. Vol. 10, p. 28 Vol. 9, p. 29) has been confirmed with ether-treated cells of P. aureofaciens. Efficient hydrolysis of (125) to (123) did, however, occur.101... 

It was of interest to see whether the betaine (171) would serve as a precursor for 2-hydroxyphenazine-l-carboxylic acid (177) and 2-hydroxyphenazine, which are produced by Ps. aureofaciens along with 1-carboxyphenazine (170). ° 2-Hydroxyphenazine-l-carboxylic acid could, it was thought, arise by opening of the epoxide ring of (172) in an alternative manner to the one which would give pyocyanin. In the event, however, only 1-carboxyphenazine served as a precursor for (177) and 2-hydroxyphenazine the respective levels of incorporation are in accord with the sequence (170)— (177)— 2-hydroxyphenazine. As 1-... 

Hydroxyphenazine-l-carboxylic acid (li) and 2-hy-droxyphenazine (lb) are believed to be derived sequentially from phenazine-1-carboxylic acid (Ih) via known biotransformation reactions, presumably via an arene oxide intermediate (Scheme 3). In Pseudomonas aureofaciens, an NADPH-dependent reductase is responsible for the hydroxylation to form li, whereas the subsequent decarboxylation to give lb occurs spontaneously and nonenzymatically. ... 

Phenazine-1-carboxylic acid, 2-hydroxyphenazine, and 2-hydroxyphenazine-l-carboxylic acid were extracted from Pseudamonas aureofaciens cultures and analyzed on a Cig column (A = 257 nm) using a 25-min 65/35/0.1 ->0/100/0.1 water/acetonitrile/TFA gradient [1001]. Elution of the components is complete in 15 min and the two carboxylic acids are not resolved using this gradient system. Therefore, it seems prudent to change to a shallower gradient or have an initial isocratic hold period prior to a gradient in order to force a separation. 

In 2013, along with the reports of biologically active compounds, derived by targeted syntheses, a multitude of natural products was found to display antibacterial, antifungal, and anticancer activities. Mehnaz and her colleagues isolated and characterized known compounds phenazine-1-carboxylic acid (159), 2-hydroxyphenazine-l-carboxylic acid (160), 2-hydroxyphenazine (161), and 2,8-dihydroxyphenazine (162) from the biocontrol strain Pseudomonas aurantiaca PB-St2 (Figure 7-9) (13JNP135). 

Analogous feeding experiments with Pseudomonas aureofaciens established that (87) but not (88) was utilised in the formation of 2-hydroxyphenazine-l-carboxylic acid (94) and 2-hydroxyphena-zine (95). These results were interpreted as showing that both of these phenazine metabolites (94 and 95) are metabolites of phenazine-1-carboxylic acid (87) and are formed as outlined above. 

Hydroxyphenazine-l-carboxylic acid (0.2% inc. in Et20-treated cells)... 

Rapid and sensitive HPLC methods were developed for the detection of an antimicrobial growth promoter and its main metabolites containing quinoxaline-2-carboxylic acid <2005MI1495>. The major phenazine pigments of Pseudomonas aeruginosa such as 1-hydroxyphenazine and phenazine-l-carboxylic acid <1997JCH(A)(771)99>, and 2-aminophenazine as an impurity in a bactericide <1999MI632>, were also analyzed by HPLC methods. 

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