Sixty-one strains of alkane-oxidizing bacteria were tested for their ability to oxidize N-(2-hexylamino-4-phenylimidazol-1-yl)-acetamide to imidazol-2-yl amino acids applicable for pharmaceutical purposes. After growth with n-alkane, 15 strains formed different imidazol-2-yl amino acids identified by chemical structure analysis (mass and nuclear magnetic resonance spectrometry). High yields of imidazol-2-yl amino acids were produced by the strains Gordonia rubropertincta SBUG 105, Gordonia terrae SBUG 253, Nocardia asteroides SBUG 175, Rhodococcus erythropolis SBUG 251, and Rhodococcus erythropolis SBUG 254. Biotransformation occurred via oxidation of the alkyl side chain and produced 1-acetylamino-4-phenylimidazol-2-yl-6-aminohexanoic acid and the butanoic acid derivative. In addition, the acetylamino group of these products and of the substrate was transformed to an amino group. The product pattern as well as the transformation pathway of N-(2-hexylamino-4-phenylimidazol-1-yl)-acetamide differed in the various strains used.Substitued imidazoles have been extensively used in medicine and agriculture. The recognition early in the last century that histamine, 2-(4-imidazolyl)ethylamine, acts as a messenger molecule in cell-to-cell communication (3,10,11) led to the development and use of antihistamine drugs, defined as H 1 , H 2 , and H 3 receptor antagonists with structures related to histamine (4, 46). Burimamid and cimetidin were described as selective H 2 receptor antagonists (4, 5), and phenoxyalkyl imidazoles have been developed as potent H 3 receptor antagonists (19). Some substituted imidazoles have antifungal activities (14,15,39,44,49,53,54), while various 1-substituted imidazoles have anticonvulsant properties (9, 21, 22, 24-26, 38, 43, 44). Furthermore, the biologically active angiotensin II receptor antagonists have an imidazole moiety (1). Apart from Nbenzylimidazoles (8), eprosartan (36), and related compounds (6, 32), imidazolylalkylamino acids are also potent angiotensin II receptor antagonists (28).Because of the manifold biological activities of imidazole derivatives, we investigated whether novel imidazol-2-yl amino acids, applicable for pharmaceutical purposes, might be synthesized from N-(2-alkylamino-4-phenylimidazol-1-yl)-acetamides by using microbial biotransformation reactions. Alkane-oxidizing bacteria should be able to oxidize the terminal methyl group of the alkylamino substituent of the N-(2-alkylamino-4-phenylimidazol-1-yl)-acetamides to yield the desired imidazol-2-yl amino acids, because the most common pathway of oxidation of alkyl chains is the monoterminal oxidation via an alcohol and an aldehyde intermediate (37,41) to the corresponding carboxylic acid. Such microbial transformation has also been found for alkyl substituents of aromatics and heteroaromatics such as phenyl alkanes (51), alkyl benzene sulfonates (55), 2,5-alkyl thiophenes (17), or 6-alkyl-2-pyrones (40) and offers an attractive route for organic synthesis to produce novel aromatic and heteroaromatic substituted...
