Asymmetric Reduction of Alkyl-3-oxobutanoates by Candida parapsilosis ATCC 7330: Insights into Solvent and Substrate Optimisation of the Biocatalytic Reaction

Abstract

Asymmetric reduction of alkyl-3-oxobutanoates mediated by Candida parapsilosis ATCC 7330 resulted in optically pure alkyl-3-hydroxybutanoates in good yields (up to 72%) and excellent enantiomeric excess (up to >99 %). A detailed and systematic optimisation study was necessary and was carried out to avoid the undesired transesterification reaction during the course of asymmetric reduction. Under optimised conditions, the (S)-alkyl hydroxyesters were produced predominantly except for the methyl ester which formed the (R)-enantiomer. To the best of our knowledge, the biocatalytic asymmetric reduction of isoamyl-3-oxobutanoate to (S)-isoamyl-3-hydroxybutanoate is reported here for the first time.

Direct observation of redox reactions in Candida parapsilosis ATCC 7330 by Confocal microscopic studies

“…Even though cells harvested at 14 h produced the same ketone at less conversion (38%), these cells were used to visualise the site of biotransformation. For several other substrates reported earlier from our lab, the 14 h harvested cells produced the desired optically pure products with maximum ee (up to >99%) 1 2 3 6 7 26 29 30 33 34 35 .…”

“…Earlier reports from our lab have shown that C. parapsilosis ATCC 7330 mediated the asymmetric reduction 1 2 3 27 and deracemisation 4 28 29 30 of aromatic/aliphatic prochiral ketones and secondary alcohols respectively. It seemed logical to use a prochiral ketone for the biocatalytic reduction which shows structural similarity to 1a for the study.…”

“…Candida parapsilosis ATCC 7330 is an established biocatalyst for the preparation of numerous optically pure aryl/ aliphatic secondary alcohols and aryl amines using different strategies namely, asymmetric reduction 1 2 3 , deracemisation 4 5 6 and oxidative kinetic resolution 7 . These optically pure secondary alcohols are produced from either prochiral ketones or racemic alcohols in reaction times as short as 5 min or even up to 24 h. These small organic molecules which are biotransformed as reported in this study, possibly enter the cells by passive diffusion i.e.…”

Yeast-Mediated Stereoselective Reduction of α-Acetylbutyrolactone

“…Microbial reduction of the carbonyl group is a convenient method for obtaining enantiomerically enriched β-hydroxyesters [3], which encouraged us to use a yeast strain in the biotransformation of α-acetylbutyrolactone. Whole-cell biocatalysts, in comparison to isolated enzymes, exhibit increased stability due to the protective cell matrix and are more profitable due to lower production costs [1].…”

Regio- and enantio-selective oxidation of diols by Candida parapsilosis ATCC 7330

“…19 Several chemical reagents have been used to selectively oxidize secondary alcohols in the presence of primary alcohols, but they are not enantioselective. [24][25][26][27][28] Mechanistically, the deracemization using C. parapsilosis ATCC 7330 proceeds via stereo-inversion, i.e., enantioselective oxidation followed by reduction [a keto intermediate was observed using high-performance liquid chromatography (HPLC)]. HXN-200 for 3-O-benzylglycerol, phenyl-1,2-ethanediol, p-chlorophenyl-1,2-ethanediol and p-methylphenyl-1,2-ethanediol.…”