Saccharomyces cerevisiae hydroxy ketones

Amides of keto acids were reduced to amides of hydroxy acids biochemically using Saccharomyces cerevisiae to give optically pure products [7059]. Refluxing with lithium aluminum hydride in ether for 6 hours reduced both the ketonic and the amidic carbonyl in A -methyl-5-phenyl-5-oxopentanamide and gave 82% yield of 5-methylamino-l-phenylpentanol [1134]. 

In 1985, we reported that reduction of a prochiral 1,3-diketone A (Figure 3.6) with fermenting baker s yeast (Saccharomyces cerevisiae) was enantioselective to give (5)-hydroxy ketone B of 98-99% ee.26 I noticed that the Baeyer-Villiger oxidation of B would furnish (S)-hydroxylactone, a building block synthetically equivalent to the terminal epoxide moiety of (+)-JH III. This idea was used for the synthesis of (+)- and (-)-JH III in 1987.27... 

The reduction of ketones into alcohols can be achieved using biocatalytic methods. Amongst the most popular of the available methods is the use of Baker s yeast, BY (Saccharomyces cerevisiae). The use of P-ketoesters as substrates leads to the corresponding p-hydroxy esters, often with high enantioselectivity. In the particular case of a-substituted P-ketoesters, the substrates spontaneously racemize, and this provides the basis for many reports of dynamic resolution reactions, some of which are described in the following discussion. In 1976, Deol and co-workers showed that cycloalkyl p-ketoesters could be reduced under dynamic resolution conditions (Fig. 9-26) >58l... 

On angular methylation with protection of the 3o -hydroxy group in the form of the tetrahydropyranyl ether, the furfurylidene derivative (180) formed the trans-C/D and the cis-C/D methyl derivatives (177) and (181), respectively, in a ratio of 1 3.8. Transacetylation, ozonolysis, and esterification of the trans-methyl derivative (177) led to the diester (178), the Dieckmann reaction of which followed by acid hydrolysis gave the hydroxy ketone (179). Oxidation of the 30 -hydroxy group of the latter and the introduction of a A -bond by bromination and dehydrobromination led to the yeast Saccharomyces cerevisiae by a known method [927], a mixture of the c -enantiomer of testosterone (182) and the Z-enantiomer of androstene-dione (183), which were separated chromatographically, was obtained with yields of 70 and 73%, respectively. The over-all yield of Z-testosterone (182) in this synthesis amounted to 2.9% on the (162) (twelve stages) and 1.1% on the unsaturated ketone (140) (16 stages) [921]. 

The ability of yeasts such as baker s yeast Saccharomyces cerevisiae) was utilized extensively by chemists to reduce carbonyl compounds to alcohols [70,71]. 2,2-Dimethylcy-clohexane-l,3-dione (56) can be reduced with fermenting baker s yeast to give the (5)-hydroxy ketone 5 (Fig. 27), which was employed extensively in terpene synthesis as shown in Fig. 5 [23]. Diastereo- and enantioselective reduction of 57 Wiih Pichia terricola KI 0117 yielded 6 (Fig. 27) [35], which was converted to both (+)-JH I [35] and (—)-JH I [72,73] (Fig. 6). Reduction of 57 with baker s yeast was nondiastereoselective [35]. 

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