Ketones, reduction with yeast

Figure 10.19 Enantioselective ketone reduction with baker s yeast in an ionic liquid...

Diols may be prepared by reduction of a-diketones or a-hydroxy ketones such as biacetyl, benzoin, and benzil. Substituted benzoins containing methoxyl and p-dimethylamino groups have been reduced catalytically over platinum oxide and by sodium amalgam and alcohol. Levorotatory propylene glycol is made from acetol, CHjCOCHjOH, by an enzymatic reduction with yeast. ... 

Even more highly selective ketone reductions are earned out with baker s yeast [61, 62] (equations 50 and 51) Chiral dihydronicotinamides give carbonyl reductions of high enantioselectivity [63] (equation 52), and a crown ether containing a chiral 1,4-dihydropyridine moiety is also effective [64] (equation 52). 

Microbial reduction has been recognized for decades as a laboratory method of preparing alcohols from ketones with exquisite enantioselectivity. The baker s yeast system represents one of the better known examples of biocatalysis, taught on many undergraduate chemistry courses. Numerous other microorganisms also produce the ADH enzymes (KREDs) responsible for asymmetric ketone reduction, and so suitable biocatalysts have traditionally been identified by extensive microbial screening. Homann et have... 

Yeast reductions have provided the synthetic organic chemist with highly versatile methods to prepare chiral alcohols from prochiral ketones of which Saccharomyces cerevisiae (baker s yeast) is the most commonly used biocatalyst. In addition to prochiral ketone reductions, hundreds of... 

Reduction of symmetrical and prochiral 1,3-diketones with yeast gives optically active 3 hydroxy ketones, which are useful chiral building blocks in organic synthesis. 

Several alternative methods with high ee s for various types of ketones are known reductions catalyzed by enzymes or baker s yeast [30] and microbial reagents [31], homogeneous hydrogenation (cf. Chapter 6.1), and stoichiometric reductions with chiral metal hydrides [32]. 

Asymmetrical reduction of ketones to alcohols66 can be done in a number of ways. Reductions with microorganisms67 were described in Chap. 9. By choosing appropriate microbes both R and S isomers were obtained. The inclusion of dimethylsulfide in a reduction of /3-ketoesters with Baker s yeast raised the enantioselectivity from 94 to 98%.68... 

In addition to baker s yeast, several systems that selectively reduce aliphatic ketones are now known. Lactic acid bacteria, e.g., Lactobacillus fermentum, Lactobacillus brevis or Leuconostoc paramesenteroides, reduce 2-pentanone or acetophenone in high yield (50- 100%) and high enantioselectivity (94-100% ee) to the (S )-configurated alcohols247. (5)-Alcohols are also obtained with high enantiomeric excess from 2-pentanone, 2-heptanone, 2-octanone and the substituted ketones 3-methyl-2-butanone and 4-methylpentane-2,3-dione by reduction with resting cells of the thermophilic archaebacterium Sulfolobus so/fataricus24s. 

In addition to baker s yeast, many other microorganisms have been used for the reduction of cyclic ketones. In contrast to the yeast transformation of 6-oxobicyclo[3.2.0]hept-2-ene to the isomeric alcohols (vide supra), the reduction with Mortierella ramaniana proceeds selectively to yield only the (6S)-eHcfe>-alcohol and unreacted optically active ketone274. If the same fungus is used for the reduction of 7.7-dimethyl-6-oxobicyclo[3.2.0]hept-2-ene a mixture of endo- and e.w-alcohols is formed275. 

Figure 4.1. Reduction of unsymmetrical ketones with yeast.

A first group of ISPR systems, most commonly with reductions, is those using the addition of a resin or porous adsorbent to remove the product. Early work on ketone reduction showed already that hydrolysis and also loss of ee could be overcome by maintaining low concentrations of the substrate in the reaction. One successful approach involves the controlled release of the substrate from a resin placed in the reaction media. For example, Amberlite XAD-2 resin enhanced the asymmetric reduction of ethyl 4-chloroacetoacetate to (S)-4hydroxybutyric acid ethyl ester catalyzed by yeast [34]. In the subsequent development of the technolt, the approach was extended to simultaneous substrate supply and product removal. A similar approach was developed for the asymmetric reduction of 6-bromo-P-tetralone [35]. 

The baker s yeast reduction of (3-keto esters has been extensively studied in the past [36]. Green cell suspension cultures obtained from bryophytes were studied by Speicher et al. in bioconversions for the enantio- or diastereoselective reduction of simple ketones, (3-keto esters, and a,(3-unsaturated carbonyl compounds [37]. These bioreductions proceed according to the Prelog s rule. It has been confirmed that bryophyte cell cultures are generally capable of ADH reductions in reactions with various substrates. One of the four possible stereoisomers was formed from the (3-keto ester 20, the anti-(2S,3S)-20b product, due to the diastereoselective reduction with concomitant DKR through in situ racemization of the substrate via enolization (Scheme 12.17). The ds-(li ,2S)-2-hydroxycyclohexane carboxylate 3a was obtained with Metrosideros polymorpha with 90-94% de and up to 90% ee [37]. 

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