Bacterial dioxygenase- and monooxygenase-catalysed sulfoxidation of benzo[b]thiophenesElectronic supplementary information (ESI) available. See DOI: 10.1039/c1ob06678a

• Main Authors: Boyd, Derek R, Sharma, Narain D, McMurray, Brian, Haughey, Simon A, Allen, Christopher C. R, Hamilton, John T. G, McRoberts, W. Colin, More O'Ferrall, Rory A, Nikodinovic-Runic, Jasmina, Coulombel, Lydie A, O'Connor, Kevin E
• Format: Article
• Language: English
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/c1ob06678a

Asymmetric heteroatom oxidation of benzo[ b ]thiophenes to yield the corresponding sulfoxides was catalysed by toluene dioxygenase (TDO), naphthalene dioxygenase (NDO) and styrene monooxygenase (SMO) enzymes present in P. putida mutant and E. coli recombinant whole cells. TDO-catalysed oxidation yielded the relatively unstable benzo[ b ]thiophene sulfoxide; its dimerization, followed by dehydrogenation, resulted in the isolation of stable tetracyclic sulfoxides as minor products with cis -dihydrodiols being the dominant metabolites. SMO mainly catalysed the formation of enantioenriched benzo[ b ]thiophene sulfoxide and 2-methyl benzo[ b ]thiophene sulfoxides which racemized at ambient temperature. The barriers to pyramidal sulfur inversion of 2- and 3-methyl benzo[ b ]thiophene sulfoxide metabolites, obtained using TDO and NDO as biocatalysts, were found to be ca. : 2527 kcal mol 1 . The absolute configurations of the benzo[ b ]thiophene sulfoxides were determined by ECD spectroscopy, X-ray crystallography and stereochemical correlation. A site-directed mutant E. coli strain containing an engineered form of NDO, was found to change the regioselectivity toward preferential oxidation of the thiophene ring rather than the benzene ring. Dioxygenase- and monooxygenase-catalysed sulfoxidation of benzo[ b ]thiophenes can yield enantioenriched chiral benzo[ b ]thiophene sulfoxides which racemize spontaneously.