Alcohol 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. 

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).

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