Application of combinatorial biocatalysis for a unique ring expansion of dihydroxymethylzearalenone

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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.

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Acknowledgments

We thank Dr. M. Muzzio, Dr. S. Hu, and L. Fischer for help with HPLC purification and analysis.

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†

Present address: Medical College of Wisconsin, Milwaukee, WI, USA.

‡

Present address: Black and Veatch Corp., Overland Park, KS, USA.

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