Reduction Baker s yeast

A series of 2-(4-chlorophenoxy)-3-oxoalkanoate were reduced by baker s yeast, and Kluyveromyces marxianus. Yeast reduction of ethyl 2-(4-chlorophenoxy)-3-oxo-3-phenylpropanoate (R=Ph) afforded enantiomerically pure ethyl 2R, 3S)-2-(4-chlorophenoxy)-3-hydroxy-3-phenylpropanoate out of the four possible stereoisomers in >99% de [29h]. Although baker s yeast reduction of butanoate (R = CFl3) was not selective (92% de), the use of K. marxianus afforded (2R, 3S)-isomer selectively [29i]. The products are intermediates for potential peroxisome prolifera-tor-activated receptor isoform a-agonists (Figure 8.39a). 

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. 

Figure 16 Baker s yeast reduction of ketones in a mixed solvent of IL with...

Baker s yeast reduction of y-nitroketones offers the corresponding chiral nitro alcohols, which are useful building blocks for the synthesis of chiral natural compounds.120 For example, optically active 2-substituted pyrrolidine can be prepared using the chiral nitro alcohol (Eq. 10.75).121... 

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% ... 

Kim and co-workers also commenced their approach (Scheme 4.13) with ketone 79, but created the stereogenic center via Baker s yeast reduction to give alcohol 83 in 91% yield with an ee of greater than 95% (Kang et al., 1996). Reduction of the nitro group... 

The carbon fragment used in this approach can also be provided by sulfur yUdes. In this arena, Metzner and co-workers <99JCS(P1)731> developed a novel asymmetric variant employing (+)-(2/J,5/J)-2,5-dimethylthiolane (53) as the chiral auxiliary to prepare rrons-(S,S)-stilbene oxide (56). Chiral epoxides have also been prepared from aldehydes using sulfur ylides derived from the products of Baker s yeast reductions <99SL1328>. 

The assignment of (/ )-2,3-dihydro-2-phenylfuran rests on Jones oxidation which furnished (ft)-dihydro-5-phenyl-2(3//)-furanone [(/ )-24]80. The configuration of the corresponding S-enantiomer (obtained by yeast reduction of 4-oxo-4-phenylbutanoic acid) was established by correlation with ethyl (S)-3-hydroxy-3-phenylpropanoate (of known configuration, obtained itself by a baker s yeast reduction) by a sequence featuring an Arndt -Eistert homologization as the key step (see also p 403)19. 

In order to synthesize the R-enantiomer of hydroxy keto ester 2a we reinvestigated the baker s yeast reduction of 3,5-dioxoesters [7]. The chlorinated diketo... 

Table 1. Baker s Yeast Reduction of Fluorinated Ketones ...

In addition, the use of enzyme selective inhibitors has turned out to be very effective. Reductions were performed by adding l,l,l-trifluoro-2,4-pentane-dione 1 to a yeast-water suspension with selected additives such as methylvinyl-ketone, allyl alcohol, alkanoic acids, ethyl chloroacetate or allyl bromide, all of them reported to affect the stereochemical course of baker s yeast reduction. In some cases, both the influence of the yeast/substrate ratio and the influence of the presence of glucose were considered. In the presence of alkanoic acids (acetic, fumaric, or oleic acid), no significant effect was observed. However, addition of methylvinyl-ketone, allyl alcohol, ethyl chloroacetate and allyl bromide to the reaction system affected the stereochemical course of the reduction of 1. In particular, (R)-(+)-2 was produced in the presence of ethyl chloroacetate and allyl bromide as additive. 

As described previously [63], P-ketoester 111 [Fig. (31)] was subjected to Baker s yeast reduction to afford the optically active P-hydroxyester 112 (60-80% yield). Dianion alkylation of 112 with (E)-3-methyl-4-(0-tert-butyldimehtylsilyl)-2-butene afforded the desired a-alkyl product 113 in 58-70% isolated yield. 

Baker s yeast reduction of organic compounds, especially carbonyl compounds, is an extremely useful method of obtaining chiral products255-257. Recently, much effort has been expended to improve the ee obtained in this process. In one very useful example, l-acetoxy-2-alkanones have been reduced enantioselectively into (5 )-l-acetoxy-2-alkanols in 60-90% yields and with 95-99% ee258. The reaction readily occurs in a variety of solvents, both aqueous and nonaqueous. The reduction is fairly selective and so may be brought about in the presence of a-amide, ether, ester and other acid functional groups, in reasonable yields and with excellent ee (equation 65)259 -261. Thus, in the synthesis of the C-13 side chain of taxol, the key step was the reduction of a w-ketoester to the corresponding alcohol in 72% overall yield (equation 66)262. 

Dynamic kinetic resolution of racemic ketones proceeds through asymmetric reduction when the substrate does racemize and the product does not under the applied experimental conditions.29 For example, baker s yeast reduction of (/ /5)-2-(4-methoxyphenyl)-l,5-benzothiazepin-3,4(2H,5H)-dione gave only (25, 35)-alcohol as a product out of four possible isomers as shown in Figure 28 (a).29a Only (5)-ketone was recognized by the enzyme as a substrate and reduction of the ketone proceeded enantioselectively. The resulting product was used for the synthesis of (25, 35)-Diltiazem, a coronary vasodilator. 

S Rodriguez, MM Kayser, JD Stewart. Improving the stereoselectivity of baker s yeast reductions by genetic engineering. Org Lett 8 1153-1155, 1999. 

M North. Baker s yeast reduction of 3-keto esters in petrol. Tetrahedron Lett 1699-1702, 1996. 

R Hayakawa, M Shimizu, T Fujisawa. The baker s yeast reduction of l-acetoxy-2-alkanones in the presence of a sulfur compound. Tetrahedron Asymmetry 8 3201-3204, 1997. 

An important application of this baker s yeast reduction is in the synthesis of citronellol. After reduction and protection of the ester, S 2 substitution of the secondary tosylate group could be achieved with inversion using a copper nucleophile. The 88% ee obtained here is better than that of many natural samples of citronellol in common with many other terpenes, citronellol extracted from plants varies greatly in enantiomeric purity. It is quite a compliment to the humble yeast that, with a bit of help from Professor Mori s research group, it can outdo most of the more sophisticated members of the plant kingdom. 

P-Galactosidase (whole cells, e.g. baker s yeast) Reduction of ketones RTIL recyclable after product distilled RTILs (alone) do not damage cell membrane... 

More recently, a four-step synthetic sequence which provides expedient access to the (—)-(f ,f )-enantiomer in 42% overall yield has been reported. This route is convenient for large-scale preparation (0.2 mol scale), and is highlighted by an asymmetric Baker s Yeast reduction of 2,5-hexanedione. Subsequent mesylation, N,N-dialkylation, and deprotection provides the enantiomerically pure free pyrrolidine (eq 3). Alternatively, either enantiomer of the chiral pyrrolidine can be obtained in 15% overall yield from an isomeric mixture of 2,5-hexanediol, via a similar sequence in which (5 )-a-methylbenzylamine is used as a chiral auxiliary. Also, an enantioselective route to either (2S,55)- or (2i ,5/ )-hexanediol has been reported. ... 

Stewart JD. A genomic approach to investigating baker s yeast reductions. In Biocatalysts in the Pharmaceutical and Biotechnology Industries. Patel RN, ed. 2007. CRC Press, Boca Raton, FL. pp. 333-350. 

Two key chiral building blocks used in the total synthesis of a-tocopherol were prepared via microbial reduction of unsaturated carbonyl compounds with baker s yeast and with Geotrichum candidum Similarly, a key intermediate in the total synthesis of optically active natural carotenoids was prepared by microbial reduction of oxoisophorone with baker s yeast. An alternative approach to the synthesis of a-tocopherol employs a chiral building block that was obtained by baker s yeast reduction of 2-methyl-5-phenylpentadienal. ... 

Intact baker s yeast resolves 2-methyl-ferrocenealdehyde kinetically, leading to 88% ee in the remaining (I )-aldehyde and 77% ee in (S)-2-methyl-ferrocenemethanol (Fig. 4-21 c) [16], A comparatively high enantiomeric excess is observed quite often in baker s yeast reductions of suitably constructed planar chiral ferrocene derivatives [18]. 

Van der Schaft, P.H., de Goede, H. and ter Burg, N. Baker s Yeast Reduction of 2,3-Pentanedione to Natural 3-Hydroxy-2-pentanone. In Flavour Science. Recent Developments (Taylor, A.J. and Mottram, D.S., eds.). Royal Society of Chemistry Information Services, pp. 134-137 (1996)... 

Howarth J, James P, Dai J (2001) ImmobUized baker s yeast reduction of ketones in an ionic Uquid, [bmim]PF6 and water mix. Tetrahedron Lett 42 7517-7519... 

Knight and Sibley began their short asymmetric synthesis of (-)-3 very similarly (Scheme 3) (41,42). Baker s yeast reduction of a 3-oxoproline ester and chemical modification of the resulting (2/J,3S)-3-hydroxyprolinate gave aldehyde... 

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