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
  • 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).

Products