Abstract:
The efficient asymmetric dihydroxylation of 6,7-epoxygeraniol was performed using a chemoenzymatic
process employing a yeast epoxide hydrolase (EH) resolution stereoinversion step, followed by
stereoretentive chemical hydrolysis of the remaining epoxide to produce (6 R)-6,7-dihydroxygeraniol
at unprecedented high enantiometic excess (ee) (>97.5%) and high isolated yield (72 mol % overall
yield over 5 steps from commercially available geraniol). The enzymatic process was completed
within 2 h at 250 g/L substrate loading reaching > 49.5 mass % conversion of the racemic epoxide.
The reaction was self-limiting and furnished both the homochiral (6 R)-triol and the residual (6 R)-
epoxide at > 99% ee, due to enantio-inversion of the (6S)-epoxide. The (6 R)-epoxide was
subsequently chemically hydrolysed, without first needing to separate the epoxide and triol
products, to afford the desired (6 R)-triol product in >97.5% ee, at multigram scale. This
chemoenzymatic procedure offers an excellent alternative to chemical asymmetric epoxidation or
dihydroxylation for the production of enantiopure 6,7-dihydroxygeranyl and 6,7-epoxygeranyl type
compounds in general. It exemplifies the benefits of using greener EH bioprocesses to produce
such compounds in high ee’s and high isolated yields.
