Application of combinatorial biocatalysis for a unique ring expansion of dihydroxymethylzearalenone |
| |
Authors: | Joseph O Rich Cheryl L Budde Luke D McConeghey Ian C Cotterill Vadim V Mozhaev Sheo B Singh Michael A Goetz Annie Zhao Peter C Michels Yuri L Khmelnitsky |
| |
Institution: | 1. AMRI, Department of Metabolism and Biotransformations, 21 Corporate Circle, Albany, NY 12212, USA;2. Merck Research Laboratories, 126 E. Lincoln Ave, Rahway, NJ 07065, USA |
| |
Abstract: | Combinatorial biocatalysis was applied to generate a diverse set of dihydroxymethylzearalenone analogs with modified ring structure. In one representative chemoenzymatic reaction sequence, dihydroxymethylzearalenone was first subjected to a unique enzyme-catalyzed oxidative ring opening reaction that creates two new carboxylic groups on the molecule. These groups served as reaction sites for further derivatization involving biocatalytic ring closure reactions with structurally diverse bifunctional reagents, including different diols and diamines. As a result, a library of cyclic bislactones and bislactams was created, with modified ring structures covering chemical space and structure activity relationships unattainable by conventional synthetic means. |
| |
Keywords: | |
本文献已被 ScienceDirect 等数据库收录! |
|