Biocatalytic enantiomeric resolution of l-menthol from an eight isomeric menthol mixture through transesterification
[Display omitted] ► Faced with the isolation of eight diastereomers with similar chemical properties we used an enzyme to selectively transform the desired isomer ( l-menthol) by esterification. ► The esterified menthol could then easily be separated from the mixture by physical means, such as disti...
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| Published in: | Journal of molecular catalysis. B, Enzymatic Vol. 75; pp. 1 - 10 |
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| Main Authors: | , , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
Amsterdam
Elsevier B.V
01-03-2012
Elsevier |
| Subjects: | |
| Online Access: | Get full text |
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| Summary: | [Display omitted]
► Faced with the isolation of eight diastereomers with similar chemical properties we used an enzyme to selectively transform the desired isomer (
l-menthol) by esterification. ► The esterified menthol could then easily be separated from the mixture by physical means, such as distillation. ► The reaction was scaled up to 2
L and used a commercial enzyme that is available in industrial quantities.
The four diastereomers of menthol and their enantiomers, namely
dl-menthol,
dl-neomenthol,
dl-neoisomenthol and
dl-isomenthol, were synthesised by the hydrogenation of thymol to yield an eight isomer liquid menthol. A suitably selective lipase was sought to preferentially esterify
l-menthol in organic solvent, hence simplifying separation from the diasteromeric mix through distillation.
From an initial screen a commercial
Pseudomonas fluorescens lipase (Amano AK) was selected, and vinyl acetate was chosen as a suitable irreversible acyl donor for transesterification. The reaction reagent ratios were optimised, and an enantiomeric excess (ee) of
l-menthol of greater than 95% was reproducibly achievable at a conversion of 30%
dl-menthol (0.68
M) at ≤50
°C. On the basis of the composition of liquid menthol the reaction had a diastereomeric excess (de) of 82%. The enzyme was recycled 150 times in 5
ml batch reactions using liquid menthol and achieving an overall yield of 184.3
g
dl-menthol/g commercial enzyme preparation. The by-product acetic acid, formed by hydrolysis of menthyl acetate, was found to cause a high degree of enzyme inactivation.
The resolution reaction was scaled up 400 fold to 2
L and the enzyme recycled 38 times with an average conversion of the available
l-menthol of 59% and a volumetric productivity of 1.2
g/L/h. |
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| Bibliography: | http://dx.doi.org/10.1016/j.molcatb.2011.10.011 |
| ISSN: | 1381-1177 1873-3158 |
| DOI: | 10.1016/j.molcatb.2011.10.011 |