Holec Claudia, Hartrampf Ute, Neufeld Katharina, Pietruszka Jörg
Institut für Bioorganische Chemie der Heinrich-Heine-Universität Düsseldorf, Forschungszentrum Jülich, Stetternicher Forst, Gebäude 15.8, 52426, Jülich, Germany.
Institut für Bio- und Geowissenschaften (IBG-1: Biotechnologie), Forschungszentrum Jülich, 52426, Jülich, Germany.
Chembiochem. 2017 Apr 4;18(7):676-684. doi: 10.1002/cbic.201600685. Epub 2017 Feb 24.
Cytochrome P450 BM3 monooxygenases are able to catalyze the regio- and stereoselective oxygenation of a broad range of substrates, with promising potential for synthetic applications. To study the suitability of P450 BM3 variants for stereoselective benzylic hydroxylation of 2-alkylated benzoic acid esters, the biotransformation of methyl 2-ethylbenzoate, resulting in both enantiomeric forms of 3-methylphthalide, was investigated. In the case of methyl 2-propylbenzoate as a substrate the regioselectivity of the reaction was shifted towards β-hydroxylation, resulting in the synthesis of enantioenriched R- and S-configured 3-methylisochroman-1-one. The potential of P450 BM3 variants for regio- and stereoselective synthesis of phthalides and isocoumarins offers a new route to a class of compounds that are valuable synthons for a variety of natural compounds.
细胞色素P450 BM3单加氧酶能够催化多种底物的区域选择性和立体选择性氧化反应，在合成应用方面具有广阔的潜力。为了研究P450 BM3变体对2-烷基化苯甲酸酯进行立体选择性苄基羟基化反应的适用性，对苯甲酸乙酯的生物转化进行了研究，该反应生成了3-甲基苯酞的两种对映体形式。以苯甲酸丙酯为底物时，反应的区域选择性转向β-羟基化，从而合成了对映体富集的R-和S-构型的3-甲基异苯并呋喃-1-酮。P450 BM3变体在区域选择性和立体选择性合成苯酞和异香豆素方面的潜力为一类化合物提供了一条新的合成途径，这类化合物是多种天然化合物的重要合成子。
