Anti-Prelog

Two interesting yeast carbonyl reductases, one from Candida magnoliae (CMCR) [33,54] and the other from Sporobolomyces salmonicolor (SSCR) [55], were found to catalyze the reduction of ethyl 4-chloro-3-oxobutanoate to give ethyl (5)-4-chloro-3-hydroxybutanoate, a useful chiral building block. In an effort to search for carbonyl reductases with anti-Prelog enantioselectivity, the activity and enantioselectivity of CMCR and SSCR have been evaluated toward the reduction of various ketones, including a- and /3-ketoesters, and their application potential in the synthesis of pharmaceutically important chiral alcohol intermediates have been explored [56-58]. 

The carbonyl reductase from Candida magnoliae catalyzed the enantioselective reduction of a diversity of ketones, including aliphatic and aromatic ketones and a- and /3-ketoesters (Figure 7.17), to anti-Prelog configurated alcohols in excellent optical purity (99% ee or higher) [56]. 

Zhu, D., Yang, Y. and Hua, L. (2006) Stereoselective enzymatic synthesis of chiral alcohols with the use of a carbonyl reductase from Candida magnoliae with anti-Prelog enantioselectivity. The Journal of Organic Chemistry, 71 (11), 4202-4205. 

Hydroxy esters have been obtained successfully with baker s yeast (Sac-charomyces cerevisidae), and this has shown a wide scope of application. The facial selectivity in the reduction of both isolated ketones and //-keto esters can be reliably determined by using Prelog s rule,8 which predicts that the hydrogen addition by the yeast will occur from the front face (Scheme 8-2). Anti-Prelog microbial reduction of a-ketones with Geotrichum sp. 38 (G38) has been introduced by Gu et al.9... 

Medici et al. have used a combined sequential oxidation-reduction to access a range of imsaturated secondary alcohols from their racemates [7] (Scheme 1). Here the S-alcohol 2 is oxidized by B. stereothermophilus which is displaying Prelog specificity leaving the l -enantiomer untouched. The other microorganism, Y. lipolytica contains an anti-Prelog dehydrogenase which is therefore able to reduce the ketone 1 to the l -alcohol 2. Thus the combination of the two steps effects a net deracemization of substrate 2. 

Figure 2.23 Enantioselective reduction of unsymmetricaUy substituted ketones by dehydrogenases yields secondary alcohols. The reaction may either follow Prelog s rule (addition of hydride from re-side) or they may not (anti-Prelog).

Dehydrogenase Reduction of aldehydes + ketones Prelog-selectivity NADH-enzymes whole cells Anti-Prelog-selectivity, NADPH-enzymes... 

Scheme 2.120 Stereocomplementary bioreduction using a Prelog and anti-Prelog dehydrogenase...

Dehydrogenase Reduction of aldehydes and ketones Prelog-selectivity, NADH-enzymes, whole cells Anti-Prelog-enzymes, NADPH-enzymes State of the art, NADH-dependent anti-Prelog enzymes ... 

Figure 9.S Biocatalytic anti-Prelog stereoselective reduction of 4 -methoxyacetophenone with immobilized Trigonopsis variabilis AS2.1611 cells in IL-containing cosolvent systems.

The presence of certain ILs might lead to a mild permeabUization of the cell membrane and thereby facilitate substrate access to the cytosol. The addition of 2.5% (v/v) [C20HMIM][N03] in aqueous buffer substantially boosted the reaction efficiency of the anti-Prelog stereoselective reduction of 4 -methoxyacetophenone to (J )-l-(4 -methoxyphenyl)ethanol with immobilized Tr onopsis variabUis cells (Figure 9.5). Also, the presence of [CzOHMIMjINOs] allowed the cells to tolerate with relatively high temperatures and substrate concentrations compared to those in aqueous buffer without IL [52]. 

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