Chemoenzymatic Synthesis of the Intermediates in the Peppermint Monoterpenoid Biosynthetic Pathway

Aisling Ní Cheallaigh, David J. Mansell, Helen S. Toogood, Shirley Tait, Antonios Lygidakis, Nigel S. Scrutton, John M. Gardiner

Research output: Contribution to journalArticlepeer-review


A chemoenzymatic approach providing access to all four intermediates in the peppermint biosynthetic pathway between limonene and menthone/isomenthone, including noncommercially available intermediates (−)-trans-isopiperitenol (2), (−)-isopiperitenone (3), and (+)-cis-isopulegone (4), is described. Oxidation of (+)-isopulegol (13) followed by enolate selenation and oxidative elimination steps provides (−)-isopiperitenone (3). A chemical reduction and separation route from (3) provides both native (−)-trans-isopiperitenol (2) and isomer (−)-cis-isopiperitenol (18), while enzymatic conjugate reduction of (−)-isopiperitenone (3) with IPR [(−)-isopiperitenone reductase)] provides (+)-cis-isopulegone (4). This undergoes facile base-mediated chemical epimerization to (+)-pulegone (5), which is subsequently shown to be a substrate for NtDBR (Nicotiana tabacum double-bond reductase) to afford (−)-menthone (7) and (+)-isomenthone (8).
Original languageEnglish
Pages (from-to)1546-1552
Number of pages6
JournalJournal of Natural Products
Issue number7
Early online date6 Jul 2018
Publication statusPublished - 27 Jul 2018


  • terpenes
  • carvone
  • biocatalysis
  • chemenzymatic

Research Beacons, Institutes and Platforms

  • Manchester Institute of Biotechnology


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