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Amino acid oxidase-catalysed resolution and Pictet-Spengler reaction towards chiral and rigid unnatural amino acids

Author:
Benz, Peter, Wohlgemuth, Roland
Source:
Journal of chemical technology and biotechnology 2007 v.82 no.12 pp. 1082-1086
ISSN:
0268-2575
Subject:
biosynthesis, enzymes, ingredients, isoquinoline alkaloids, metabolites, oxidation, receptors, tyrosine
Abstract:
BACKGROUND: The biosynthesis of structurally complex isoquinoline alkaloids and other natural products occurs via aromatic amino acids such as tyrosine, and chiral and rigid amino acids. These structures are also key building blocks of many active pharmaceutical ingredients. The aim of this work was the exploration of a rapid and straightforward route to chiral 6-hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid.RESULTS: The preparation of (S)-meta-tyrosine from racemic meta-tyro- sine with aminoacidoxidase has been developed with ee > 99% and 88% yield. The combination of this resolution with a subsequent Pictet-Spengler reaction enables straightforward and versatile access to chiral (S)-6-hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid in 30% yield.CONCLUSIONS: This new short chemoenzymatic route to (S)-6-hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid from commercially available DL-m-tyrosine is more convenient than other chemical procedures and establishes a new link between the pool of easily accessible racemic aromatic amino acids and the corresponding chiral rigidified amino acids, which are of interest as structural elements of many active pharmaceutical ingredients. These results facilitate synthetic access to a range of active pharmaceutical ingredients and metabolites in chiral form from the oxidation of amino acids. This advances the opportunities to study the molecular interactions with enzymes, receptors and effectors more precisely than with the racemic forms.
Agid:
273157