2. Academic Validation
  3. Chemoenzymatic Synthesis of the Intermediates in the Peppermint Monoterpenoid Biosynthetic Pathway

Chemoenzymatic Synthesis of the Intermediates in the Peppermint Monoterpenoid Biosynthetic Pathway

  • J Nat Prod. 2018 Jul 27;81(7):1546-1552. doi: 10.1021/acs.jnatprod.7b01026.
Aisling Ní Cheallaigh 1,  David J Mansell 1,  Helen S Toogood 1,  Shirley Tait 1,  Antonios Lygidakis 1,  Nigel S Scrutton 1,  John M Gardiner 1
Affiliations

Affiliation

  • 1 BBSRC/EPSRC Manchester Synthetic Biology Research Centre for Fine and Speciality Chemicals (SYNBIOCHEM), Manchester Institute of Biotechnology and School of Chemistry , The University of Manchester , 131 Princess Street , Manchester M1 7DN , U.K.
PMID: 29979593 DOI: 10.1021/acs.jnatprod.7b01026
Abstract

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).

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