Preparation of 4-(4'-hydroxyanilino)-5-anilinophthalimide and 4,5-bis-(4'-hydroxyanilino)-phthalimide by microbial hydroxylation

• Published in: Bioscience, biotechnology, and biochemistry Vol. 63; no. 8; pp. 1497 - 1500
• Main Authors: Weidner, S. (Novartis Pharma AG, Basel (Switzerland)), Goeke, K, Trinks, U, Traxler, P, Ucci-Stoll, K, Ghisalba, O
• Format: Journal Article
• Language: English
• Published: Tokyo Japan Society for Bioscience, Biotechnology, and Agrochemistry 01.01.1999; Japan Society for Bioscience Biotechnology and Agrochemistry; Oxford University Press
• Subjects: 4,5-bis-(4′-hydroxyanilino)-phthalimide; 4-(4′-hydroxyanilino)-5-anilinophthalimide; BEAUVERIA BASSIANA; Bioconversions. Hemisynthesis; Biological and medical sciences; Biotechnology; CUNNINGHAMELLA; Fundamental and applied biological sciences. Psychology; HIDROXILACION; HYDROXYLATION; Methods. Procedures. Technologies; microbial hydroxylation; PTK-inhibitors; STREPTOMYCES; Streptomycetaceae; Hydroxylation; Enzyme; Transferases; Enzyme inhibitor; Streptomyces; Actinomycetales; Fungi; Beauveria bassiana; Imide; Preparative scale; Biotransformation; Production; Bacteria; Actinomycetes; Fungi Imperfecti; Protein-tyrosine kinase; Thallophyta; 4-(4′-hydroxyanilino)-5-anilinophthalimide; PTK-inhibitors; microbial hydroxylation; 4,5-bis-(4′-hydroxyanilino)-phthalimide
• ISSN: 0916-8451; 1347-6947
• DOI: 10.1271/bbb.63.1497

A microbial screening indicated that two fungal strains, Beauveria bassiana DSM 1344=ATCC 7159 and Cunninghamella elegans DSM 1908=ATCC 9245, as well as four bacterial strains belonging to the genus Streptomyces were able to hydroxylate 4,5-dianilinophthalimide (DAPH, CGP52411) to 4-(4′-hydroxyanilino)-5-anilinophthalimide. Cunninghamella elegans DSM 1908 turned out to be the most active biocatalyst and was also able to form the dihydroxy derivative, 4,5-bis(4′-hydroxyanilino)phthalimide. The reaction for the monohydroxylated biotransformation product was carried out on a preparative scale, and the culture conditions for the formation of 4-(4′-hydroxy- anilino)-5-anilinophthalimide with this strain were op-timized.