Yeast-mediated stereoselective reactions

A familiar example of a stereoselective reaction would be the formation of a higher yield of f rans-2-butene than cis-2-butene in an E2 reaction, no matter whether the starting material is (R)- or (S)-2-bromobutane. The addition of bromine to trans-2-butene to produce mcso-2,3-dibromobutane or the addition of bromine to the cis isomer to produce an equimolar mixture of the two enantiomers of 2,3-dibromobutane is a stereospecific reaction. Note that a reaction that gives only one of a pair of eirantiomers is not necessarily stereospecific. A yeast-mediated reduction of 3-chloropropiophenone gives (S)-3-chloro-l henylpropan-l-ol, with no evidence for formation of the R enantiomer. Because the reactant cannot exist as stereoisomers, it is not possible for stereoisomerically different reactants to give stereoisomerically different products, and the reaction can only be considered stereoselective, not stereospecific. 

It seems that the enantioselectivity of the reduction of keto esters with the keto group being part of a five-membered ring proceeds better than that of open-chain keto esters substituted at carbon C-2 [225, 226]. The reduction of 50 (Figure 21.16) gave 80% of (1R,2S)-51 showing both an ee and a de of 100%. In another experiment, however, 51 was obtained with a de of only 60% [217, 227]. Several mold strains have been shown to perform the same reduction with high enanho- and dias-tereoselection, whereas from the baker s yeast-mediated reactions quite often mixtures of the stereoisomeric products were obtained [227]. More complex substrates have also been studied [228-232], but yields and /or stereoselectivity were often only moderate. 

Asymmetric oxidoreductions performed in isopropyl ether allow syntheses of optically active alcohols with ee >95% on a 1-10 mmol scale. Nakamura et al. investigated the effect of organic solvents on the reduction of ot-keto esters mediated by bakers yeast [140]. The reduction of ethyl 2-oxoheptanoate was tested in various solvents. Best results were achieved with benzene so further experiments were performed with benzene. Conversion only takes place in the presence of small amounts of water. The reduction of six ot-keto esters was examined regarding the stereoselectivity of the corresponding ot-hydroxy esters. The reactions were performed in aqueous systems as well as in benzene. In aqueous systems, the formed hydroxy esters show (S)-stereoselectivity while the stereochemistry of the reaction shifts markedly towards the production of (/ )-ot-hydroxy esters in benzene. 

Stereoselective carbon-carbon bond-forming reactions are among the most useful S5mthetic methods in asymmetric synthesis as they allow the simultaneous creation of up to two adjacent stereocenters. Acyloin formation mediated by thiamine diphosphate-dependent decarboxylase, yeast pyruvate decarboxylase, bacterial benzoylformate decarboxylase, and phenylpyruvate decarboxylase has been reported [142-147]. 

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