Biocatalytic Aromaticity-Breaking Epoxidation of Naphthalene and Nucleophilic Ring-Opening Reactions

Wuyuan Zhang; Huanhuan Li; Sabry H H Younes; Patricia Gómez de Santos; Florian Tieves; Gideon Grogan; Martin Pabst; Miguel Alcalde; Adrian C Whitwood; Frank Hollmann

doi:10.1021/acscatal.0c05588

Biocatalytic Aromaticity-Breaking Epoxidation of Naphthalene and Nucleophilic Ring-Opening Reactions

ACS Catal. 2021 Mar 5;11(5):2644-2649. doi: 10.1021/acscatal.0c05588. Epub 2021 Feb 12.

Authors

Wuyuan Zhang^{1

2}, Huanhuan Li³, Sabry H H Younes^{1

4}, Patricia Gómez de Santos⁵, Florian Tieves¹, Gideon Grogan⁶, Martin Pabst¹, Miguel Alcalde⁵, Adrian C Whitwood⁷, Frank Hollmann¹

Affiliations

¹ Department of Biotechnology, Delft University of Technology, Van der Maasweg 9, 2629HZ Delft, The Netherlands.
² Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, 32 West 7th Avenue, Tianjin 300308, China.
³ School of Chemical Engineering and Technology, Xi'an Jiaotong University, Xi'an 710049, China.
⁴ Department of Chemistry, Faculty of Sciences, Sohag University, Sohag 82524, Egypt.
⁵ Department of Biocatalysis, Institute of Catalysis, CSIC, 28049 Madrid, Spain.
⁶ York Structural Biology Laboratory, Department of Chemistry, University of York, YO10 5DD York, U.K.
⁷ Department of Chemistry, University of York, YO10 5DD York, U.K.

Abstract

Aromatic hydroxylation reactions catalyzed by heme-thiolate enzymes proceed via an epoxide intermediate. These aromatic epoxides could be valuable building blocks for organic synthesis giving access to a range of chiral trans-disubstituted cyclohexadiene synthons. Here, we show that naphthalene epoxides generated by fungal peroxygenases can be subjected to nucleophilic ring opening, yielding non-racemic trans-disubstituted cyclohexadiene derivates, which in turn can be used for further chemical transformations. This approach may represent a promising shortcut for the synthesis of natural products and APIs.