Diols with bakers’ yeast

Again with Bakers yeast it was shown that diols 22 and 23 could be produced as shown in Scheme 6.8 [15]. The diketone 21 was dissolved in DMF and when added to the Bakers yeast media, high enantiomeric excesses were obtained. 

Hydroxy ketones and hydroxy-a,/3-unsaturated ketones in the steroids such as estrone and testosterone, respectively, can be reduced to diols biochemically. Estrone acetate gave 68% yield of a-estradiol on incubation with baker s yeast at room temperature after five days [909]. Testosterone was reduced by bacteria to the saturated hydroxy ketones, etiocholan-17-ol-3-one and androstan-17-ol-3-one, and further to the diols, ep/-etiocholane-3,17-diol and the epimeric isoandrostane-3,17-diol, both in low yields [329]. 

The unsaturated aldehydes 675 undergo363,364 an enantioface-dif-ferentiating reaction when treated with fermenting bakers yeast, furnishing optically active diols 676. 

If the 1,2-diketone l-(l.3-dithian-2-yl)-1,2-propanedione (7) is treated with baker s yeast, the /i-keto group is reduced much faster than the a-keto group. Therefore, it is possible to obtain (S)-hydroxy ketone 8 (60% yield), by ensuring a short reaction time (2 h), and (S,S)-anti-diol 9 (82% yield), when the reaction time is longer (48 h)220. 

Synthesis of the enantiomerically pure (5)-chroman-2-carbaldehyde (257) follows a similar route to the above, but the chirality is introduced through the ketone (256) (82CC205). A particularly interesting feature of this synthesis is the derivation of the diol (255) from 2-methyl-3-(2-furyl)propenal using fermenting baker s yeast. Furthermore, the fermentation also produces the chiral alcohol (258), a source of the C15 unit which is the second component along with the aldehyde (257) in an a-tocopherol synthesis. 

The first asymmetric total synthesis of acosamine and daunosamine starting from a nonsugar precursor was reported by Fuganti and co-workers [288,289,290,291]. They found that baker s yeast catalyzes the asymmetric pinacolic cross-coupling of cinnamaldehyde and ethenal giving a ft-diol 156. This diol is protected as an acetonide and submitted to ozonolysis giving L-157. Olefination of L-157 with PhsP = CHCOOMe, followed by treatment with ammonia, provides 158 that is then converted into W-trifluoroacetylacosamine 158 (O Scheme 61). 

In general, 1.2-diones are good substrates for baker s yeast reduction, however, selectivity is low. In most cases a racemic mixture of the hydroxy ketones and the 1,2-diols is obtained. One exception Lo this rule is the reduction of 1-phenyl-1,2-propanedione to LS )-2-hydroxy-l -phenyl-propanone by baker s yeast in phosphate buffer at pH 5217. If the reaction is carried out with a large excess of yeast in distilled water, the (1 / ,2S)-1-phenyl-1,2-propanediol is obtained in high chemical and optical yield222. 

Aliphatic a-hydroxy ketones are easily reduced by baker s yeast to yield the (7 )-configurated 1,2-diols. The reduction of l-hydroxy-2-propanone to (/ )- ,2-propanediol is still of preparative interest227,232. The corresponding a-hydroxy ketones with higher alkyl chain length are also reduced in high enantioselectivity with moderate to high yield. 

Scheme 19.21 One-pot synthesis of 1,2-diols based on combination of chemical O-acetyl a-haloketone formation and two biotransformations with a lipase and baker s yeast, respectively.

Regio- and enantioselective reduction of diketones have been conducted successfully by biocafalysis. Examples for the reduction of diketones to hydroxyl ketones and diols are shown in Figure 11.11. Figure 11.11a shows the preparation of a key intermediafe for the synthesis of terpenoids by a baker s yeast-catalyzed reduction of a o-cyclohexanedione. DMSO (10%) was used to solubilize the substrate [67]. Figure 11.11b shows the reduction of 3,5-dioxo-6-(benzyloxy)hexanoic acid ethyl ester by Acinetobacter sp. SC 13874 to the corresponding si/n-(3R,5S)-diol, potential intermediates for die s)mthesis of HMG-CoA reducfase inhibitors, in 99.4% ee with 52-74% de depending on substrate concentrations (74% de in 2g/l and 52% de in lOg/1) [66]. After the reaction, XAD-16 resin was added to facilitate the recovery process by adsorbing the product. 

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