Regioselective preparation of 5-hydroxypropranolol and 4'-hydroxydiclofenac with a fungal peroxygenase

Kinne, Matthias; Poraj-Kobielska, Marzena; Aranda, Elisabet; Ullrich, René; Hammel, Kenneth E; Hofrichter, Martin (2009). Regioselective preparation of 5-hydroxypropranolol and 4'-hydroxydiclofenac with a fungal peroxygenase. Bioorganic and medicinal chemistry letters, 19(11), pp. 3085-7. New York, N.Y.: Pergamon 10.1016/j.bmcl.2009.04.015

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An extracellular peroxygenase of Agrocybe aegerita catalyzed the H(2)O(2)-dependent hydroxylation of the multi-function beta-adrenergic blocker propranolol (1-naphthalen-1-yloxy-3-(propan-2-ylamino)propan-2-ol) and the non-steroidal anti-inflammatory drug diclofenac (2-[2-[(2,6-dichlorophenyl)amino]phenyl]acetic acid) to give the human drug metabolites 5-hydroxypropranolol (5-OHP) and 4'-hydroxydiclofenac (4'-OHD). The reactions proceeded regioselectively with high isomeric purity and gave the desired 5-OHP and 4'-OHD in yields up to 20% and 65%, respectively. (18)O-labeling experiments showed that the phenolic hydroxyl groups in 5-OHP and 4'-OHD originated from H(2)O(2), which establishes that the reaction is mechanistically a peroxygenation. Our results raise the possibility that fungal peroxygenases may be useful for versatile, cost-effective, and scalable syntheses of drug metabolites.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Gynaecology
UniBE Contributor:	Scheibner, Katrin
ISSN:	0960-894X
Publisher:	Pergamon
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 15:12
Last Modified:	05 Dec 2022 14:22
Publisher DOI:	10.1016/j.bmcl.2009.04.015
PubMed ID:	19394224
Web of Science ID:	000265981900042
URI:	https://boris.unibe.ch/id/eprint/31602 (FactScience: 196223)