Monooxygenase- and Dioxygenase-Catalyzed Oxidative Dearomatization of Thiophenes by Sulfoxidation, cis -Dihydroxylation and Epoxidation

Derek R. Boyd*, Narain D. Sharma, Paul J. Stevenson, Patrick Hoering, Christopher C. R. Allen, Patrick M. Dansette

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

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Abstract

Enzymatic oxidations of thiophenes, including thiophene-containing drugs, are important for biodesulfurization of crude oil and drug metabolism of mono- and poly-cyclic thiophenes. Thiophene oxidative dearomatization pathways involve reactive metabolites, whose detection is important in the pharmaceutical industry, and are catalyzed by monooxygenase (sulfoxidation, epoxidation) and dioxygenase (sulfoxidation, dihydroxylation) enzymes. Sulfoxide and epoxide metabolites of thiophene substrates are often unstable, and, while cis-dihydrodiol metabolites are more stable, significant challenges are presented by both types of metabolite. Prediction of the structure, relative and absolute configuration, and enantiopurity of chiral metabolites obtained from thiophene enzymatic oxidation depends on the substrate, type of oxygenase selected, and molecular docking results. The racemization and dimerization of sulfoxides, cis/trans epimerization of dihydrodiol metabolites, and aromatization of epoxides are all factors associated with the mono- and di-oxygenase-catalyzed metabolism of thiophenes and thiophene-containing drugs and their applications in chemoenzymatic synthesis and medicine.
Original languageEnglish
Article number909
JournalInternational Journal of Molecular Sciences
Volume23
Issue number2
DOIs
Publication statusPublished - 14 Jan 2022

Keywords

  • thiophene
  • thiophene epoxide
  • thiophene S-oxide
  • S-oxide dimer
  • thiophene cis- and trans-dihydrodiols
  • thiophene hydrate
  • dioxygenase
  • monooxygenase
  • cytochrome P450
  • drug metabolism

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