Pyochelin and Related Structures

This group comprises condensation products of salicylic acid with cysteine giving a thiazoline ring. For a review, see (570). Some structurally related compounds will also be mentioned here. Salicylic acid isolated from Burkholderia Pseudomonas) cepacia was named azurochelin (555). It was found to act as a siderophore, e.g. for Pseudomonas fluorescens (230) and P. syringae (178) see also Mycobacterium smegmatis (Sect. 2.8). For details on the siderophore activity of salicylic acid, see (559). 

The stmcture of pyochelin (for a detailed bibliography, see (57)), a secondary siderophore of Pseudomonas aeruginosa and of Burkholderia cepacia was established (75) as 2-(2-o-hydroxyphenyl-2-thiazolin -yl)-3-methylthiazolidine-4-carboxylic acid. It consists of a mixture of two easily interconvertible stereoisomers (pyochelin I and II) differing in the configuration of C-2 . They can be separated by chromatography, but in methanolic solution (not in DMSO) the equilibrium (ca. 3 1) is restored quickly. For a discussion of the mechanism of isomerization, see (57, 577). 

Several syntheses resulting in mixtures of stereoisomers (C-4 and C-2 ) have been developed (6,301,397) (Sect. 8.5). Pseudomonas fluorescens CHAO produces enantio-pyochoYm (394). The two optical antipodes are not accepted reciprocally by the two Pseudomonas species. 

Pyochelin is a non-ribosomal condensation product of salicyhc acid with two molecules of cysteine (289). Intermediates with one cysteine unit are aeruginoic acid (Fig. 21, 67) first isolated from Pseudomonas aeruginosa (390), and (-l-)-(5)-4,5-dihydroaeruginoic acid, from Pseudomonas fluorescens (57). Detailed studies (274a) suggest that M-hydroxybenzoyl-L-cysteine bound to the synthetase 

Micacocidin (Fig. 22, 68) from Pseudomonas sp. complexes Fe and other metal ions 189,190). Whether it acts as a siderophore has not been investigated. A stereospecific synthesis was elaborated 161,161a), but the same isomerization problems at C-4 and C-2 were encountered as had been observed with pyochelin (see Note 14 in 161)). 

---