Baker’s yeast-mediated reduction

Figure 1 Strategy for tailoring the stereoselectivity of whole-cell baker s yeast-mediated reductions. The level of a yeast reductase can be increased by placing the corresponding gene under control of a strong yeast promoter on an extrachromosomal plasmid. Alternatively, the catalytic activity of a reductase can be eliminated by replacing the corresponding gene on the chromosome with a defective copy prepared in vitro. (Reprinted with permission from Organic Letters 1999, 1. 1999 American Chemical Society.)...

MM Kayser, MD Mihovilovic, J Kearns, A Feicht, JD Stewart. Baker s yeast-mediated reductions of a-keto-(3-lactam. Two routes to the paclitaxel side chain. J Org Chem 64 6603-6608, 1999. 

V Crocq, C Masson, J Winter, C Richard, G Lemaitre, J Lenay, M Vivat, J Buendia, D Prat. Synthesis of trimegestone the first industrial application of baker s yeast mediated reduction of a ketone. Org Proc Res Dev 1 2-13, 1997. 

An important technical issue is the large-scale applicability of co-factor-dependent enzymatic systems. It is generally accepted that, e.g., NADH-requiring oxidoreductases can easily be used in whole-cell biocatalysis such as baker s yeast-mediated reductions, where the cofactor recycling step is simultaneously performed within the intact cell, driven by the reduction equivalents introduced via the external carbon and energy source (glucose). 

Kayser MM, Mihovilovic MD, Kearns J, Feicht A, Stewart JD (1999) Baker s Yeast-Mediated Reductions of a-Keto Esters and an o -Keto-/ -Lactam. Two Routes to the Paclitaxel Side Chain. J Org Chem 64 6603... 

In 1999, an efficient DKR in the context of baker s yeast mediated reductions of 2-benzenesulfonylcycloalkanones was reported. Again, the best results were observed with five- or six-membered ring derivatives, whereas the seven-and eight-membered ring compounds showed much less efficiency (Scheme 3.3). 

Brerma, E Fronza, G., Fuganti, C., Gatti, F.G., Manffedi, A., Parmeggiani, F and Ronchia, P. (2012) On the stereochemistry of the baker s yeast-mediated reduction of regioisomeric unsaturated aldehydes examples of enantioselectivity switch promoted by substrate-engineering./. Mol. Catal. B, 84, 94-101. 

Serra, S., Fronza, G., and Fuganti, C. (2008) Stereochemical course of baker s yeast mediated reduction of the tri- and tetrasubstituted double bonds of substituted cinnamaldehydes. Eur. J. Org. Chem., 2009, 6160-6171. 

Fuganti, C., Pedrocchi Fantoni, G., Sarra, A., and Servi, S. (1994) Stereochemistry of baker s yeast mediated reduction of a, 3-unsaturated 6-lactones in the goniothalamin series. Tetrahedron Asymmetry, 5, 1135-1138. 

Dumanski, P.G., Florey P., Knettig, M., SmaDridge, A.J., and Trewhella, M.A. (2001) The baker s yeast mediated reduction of conjugated methylene groups in an organic solvent J. Mol. 

L. Wang, W. Wang, 1. Cuui, W. Ren, N. Meng, 1. Wang, X. Qian, Preparation of chiral trans-5-substituted-acenaphthene-l,2-diols by Baker s yeast-mediated reduction of 5-substituted-acenaphthylene-l,2-diones. Tetrahedron Asymm. 21 (2010) 825-830. 

Perrone MG, Santandrea E, Scilimati V. Tortorella V, CapiteUi F, Bertolasi V. Baker s yeast-mediated reduction of ethyl 2-(4-chlorophenoxy)-3-oxoalkanoates intermediates for potential PPARalpha ligand. Tetrahedron Asymmetry 2004 15 3501-3510. 

Baker s Yeast-mediated Asymmetric Reduction of Fluorinated Ketones. 

R and Moran, P.J.S. (2004) Baker s yeast mediated asymmetric reduction of cinnamaldehyde derivatives./. Mol. Catal. B Enzym., 29,41 5. 

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. 

An IL solvent system is applicable to not only lipase but also other enzymes, though examples are still limited for hpase-catalyzed reaction in a pure IL solvent. But several types of enzymatic reaction or microhe-mediated reaction have been reported in a mixed solvent of IL with water. Howarth reported Baker s yeast reduction of a ketone in a mixed solvent of [hmim] [PFg] with water (10 1) (Fig. 16). Enhanced enantioselectivity was obtained compared to the reaction in a buffer solution, while the chemical yield dropped. 

Int. Ed. 2000, 39, 4355—4356 they also reported the organocopper-mediated 1,3-sub-stitution of a chiral propargyl mesylate, prepared by Baker s yeast reduction, to afford an optically active allene with 89% ... 

III. MULTIPLE BAKER S YEAST REDUCTASES AND STEREOSELECTIVITY IN WHOLE CELL-MEDIATED REDUCTIONS... 

K Nakamura, S Kondo, Y Kawai, A Ohno. Stereochemical control in microbial reduction. XXL Effect of organic solvents on reduction of a-keto esters mediated by baker s yeast. Bull Chem Soc Jpn 66 2738-2743, 1993. 

Scheme 9 Enzyme-mediated chemical transformations. (A) Enatioselective enzymatic oxidation and lactonization (B) enzyme reduction with baker s yeast and enantioselective rule and (C) enzymatic hydrolytic desymmetrization.

Reaction of lithiodithianes with acyl chlorides, esters or nitriles leads to the formation of 1,2-dicarbonyl compounds in which one of the carbonyl groups is protected as the thioacetal. 476.243.244 Optically active amino ketones of type (69) are inepared via acyl on of dithiane with an oxazoline-prote ed (S)-serine methyl ester (Sch e 41). Optically active (S)-2-alkoxy-l-(l,3-dithian-2-yl)-l-propanenantioselective synthesis of (-)-trachelanthic acid. Enantioselective synthesis of L-glyceraldehyde involves the acylation of a dithiane glycolic acid derivative followed by bakers yeast mediated reduction. ... 

Bakers s yeast is the most widely employed biocatalyst for asymmetric ketone reductions [43]. A group at Roussel Uclaf described an industrial application of bakers yeast mediated ketone reduction for the synthesis of trimegestone [44], a progestomimetic compound for the treatment of postmenopausal diseases. The key step of the nine-step synthesis is a chemo-, regio- and stereoselective bakers yeast reduction of the triketone 5 (Scheme 4.9). This transformation could not be performed efficiently using nonenzymatic methods. 

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