Green asymmetric reduction of acetophenone derivatives: Saccharomyces cerevisiae and aqueous natural deep eutectic solvent
- 29 Downloads
Chiral building blocks [(S)-1-(3-methylphenyl)ethanol, (S)-1-(3,4-dimethylphenyl)ethanol and (S)-1-(2,4,6-trimethylphenyl)ethanol] for drug synthesis were prepared using two green approaches: (1) the yeast Saccharomyces cerevisiae as the biocatalyst and (2) the natural deep eutectic solvents (NADES) as the alternative solvents. Three different NADES with different water contents were prepared and screened for the highest conversion and enantiomeric excess of reduction of 1-(3-methylphenyl)ethanone, 1-(3,4-dimethylphenyl)ethanone (DMPA) and 1-(2,4,6-trimethyphenyl)ethanone by S. cerevisiae. The results were used in the development of eco-friendly procedures on a preparative scale.
The highest enantioselectivity of baker´s yeast was for the bioconversion of DMPA in choline chloride:glycerol with 30% (v/v) of water (ChGly30). This reaction was used for further studies. Parameters such as pre-treatment of biocatalysts and recyclation of solvent were tested for a possible scale-up of this reaction system. Conversion was improved with the ultrasound pre-treatment of the biocatalysts in ChGly30. Moreover, the biocatalytic asymmetric reduction of DMPA in ChGly30 was successfully performed on a preparative scale with the efficient recyclation of NADES in two cycles, in which the reduction of DMPA was also successfully performed.
Three enantioselective reductions in NADES with baker’s yeast were successfully conducted. According to the highest enantioselectivity of the biocatalyst, the asymmetric reduction of 1-(3,4-dimethylphenyl)ethanone in ChGly30 was also performed on a preparative scale with efficient recyclation and reuse of NADES as a first step towards the implementation of this method on the industrial scale.
KeywordsAcetophenones Bioreduction Natural deep eutectic solvents Saccharomyces Cerevisiae
The work was supported by the Croatian Science Foundation (Grant No. 9550).
Figure 1S. Time—course of acetophenones bioreductions with baker’s yeast (Fig 1S).
- Contente ML, Serra I, Palazzolo L, Parravicini C, Gianazza E, Eberini I, Pinto A, Guidi B, Molinaria F, Romano D (2016) Enzymatic reduction of acetophenone derivatives with a benzil reductase from Pichia glucozyma(KRED1-Pglu): electronic and steric effects on activity and enantioselectivity. Org Biomol Chem 14:3404–3408CrossRefPubMedGoogle Scholar
- Patel RN (2004) Biocatalytic synthesis of chiral pharmaceutical intermediates. Food Technol Biotechnol 42:305–325Google Scholar
- Rodrigues JAR, Moran PJS, Conceição GJA, Fardelone LC (2004) Recent advances in the biocatalytic asymmetric reduction of acetophenones and α.β-unsaturated carbonyl compounds. Food Technol Biotechnol 42:295–303Google Scholar