Bacterial dioxygenase- and monooxygenase-catalysed sulfoxidation of benzo[b]thiophenes

Derek R. Boyd, Narain D. Sharma, Brian McMurray, Simon A. Haughey, Christopher C. R. Allen, John T. G. Hamilton, W.Colin McRoberts, Rory A. More O'Ferrall, Jasmina Nikodinovic-Runic, Lydie A. Coulombel, Kevin E. O'Connor

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

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.: 25-27 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.
Original languageEnglish
Pages (from-to)782-790
Number of pages9
JournalOrganic & biomolecular chemistry
Volume10
Issue number4
Early online date01 Dec 2011
DOIs
Publication statusPublished - 28 Jan 2012

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Biochemistry

Fingerprint Dive into the research topics of 'Bacterial dioxygenase- and monooxygenase-catalysed sulfoxidation of benzo[b]thiophenes'. Together they form a unique fingerprint.

Cite this