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
Full text not available from this repository. (Request a copy)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) |
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