Geotrichum candidum reduction

Figure 8.23 Reduction of ketones with Geotrichum candidum in the presence of hydrophobic polymer XAD [19a],...

O Water absorbing polymer Figure 8.26 Asymmetric reduction of ketones in CO2 by Geotrichum candidum immobilized whole cell [20], (a) Time course for the reduction of o-fluoroacetophenone (b) substrate specificity (c) apparatus for C. candidum-cata yzed reduction with semiflow process using scC02. 

Figure 20 Use of IL as reaction medium for asymmetric reduction by Geotrichum candidum.

Nakamura, K., Inoue, Y., Matsuda, T. and Misawa, I., Stereoselective oxidation and reduction by immobilized Geotrichum candidum in an organic solvent. J. Chem. Soc. Perkin Trans. 1, 1999, 2397-2402. 

SYNTHESIS OF BOTH ENANTIOMERS OF 1-PHENYLETHANOL BY REDUCTION OF ACETOPHENENONE WITH GEOTRICHUM CANDIDUM IFO 5767... 

Microbial reduction of ketones is a useful method for the preparation of optically active secondary alcohols. Recently, both enantiomers of secondary alcohols were prepared by reduction of the corresponding ketones with a single microbe.Thus, reduction of aromatic ketones with Geotrichum candidum IFO 5767 afforded the corresponding 5-alcohols in an excellent ee when Amberlite XAD-7, a hydro-phobic polymer, was added to the reaction system the same microbe afforded... 

Patel RN, McNamee CG et al (1992) Stereoselective reduction of P-keto esters by Geotrichum candidum. Enzyme Microb Technol 14 731-738... 

Recently, we [67] have described the reduction of the methyl ester of 4-chloro-3-oxobutanoic acid (39) to the methyl ester of S-( )-4-chloro-3-hydroxy-butanoic acid (40) (Fig. 13) by cell suspensions of Geotrichum candidum SC 5469., S ( )-(40) is a key chiral intermediate in the total chemical synthesis of a cholesterol antagonist (SQ 33600), which acts by inhibiting hydroxymethylglu-taryl CoA (HMG CoA) reductase. In the biotransformation process, a reaction... 

In another study, screening was carried out for reduction of substituted benzazepin-2,3-dione 23 to a 3-hydroxy derivative 24 (Scheme 19.14). This was accomplished by a bacterial strain of Rhodococcus fascians ATCC 12975 (Norcardia salmonicolor SC 6310) with a conversion of 97% and an optical purity of >99.9%. This reaction product 24 is a key intermediate in the synthesis of the calcium antagonist SQ 31,765 (25).104 105 The Bristol-Myers Squibb group has also shown the selective reduction of the (3-keto ester, methyl-4-chloro-3-oxobutanoate, by the fungus Geotrichum candidum SC 5469 to the corresponding (,S )-hydroxy ester.106... 

Similarly, the enantioselective reduction of prochiral ketones catalyzed by whole cells of Geotrichum candidum proceeded smoothly in scC02 in a semi-continuous flow system (Fig. 7.27) [94]. 

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. ... 

DNA sequence of 12 million nucleotides and 6000 genes has been determined.165 It can be used to reduce /3-ke-toesters in petrol plus a small amount of water to the S alcohol ester in 100% conversion with more than 98%ee.166 When only water is used as the medium, the enantioselec-tivity is reduced greatly.167 In contrast with baker s yeast and Geotrichum candidum,168 which produce the S alcohols from the reduction of ketones, Yarrowia lipolytica gives the R isomer, but in only moderate yields.169 Pichia farinosa also produces the R isomer.170 (For more on the preparation of single optical isomers, see Chap. 10.) Other reductions can also be carried out with baker s yeast as shown in 9.15 for the quinoline oxide.171... 

A dried cell mass is often used as a biocatalyst for a reduction, since it can be stored for a long time and can be used whenever needed, without cultivation. One of the useful methods to dry the cell mass is acetone dehydration[801. For example, the cells of Geotrichum candidum IFO 4597 were mixed with cold acetone (-20 °C) and the cells were collected by filtration120, 21L The procedure was repeated five times and then the cells were dried under reduced pressure. The dried cells (acetone powder of G. candidum IFO 4597 APG4) were obtained they can be stored for a long time in the freezer. 

For example, the effect of cultivation time and different carbon sources on the enantioselectivity of the reduction of sulcatone by some anaerobic bacteria has been investigated [8 if Another example is the investigation on the effect of the medium concentrations for cultivation of Geotrichum candidum IFO 4597 on the enantioselectivity of the reduction of acetophenone derivatives. The yield of l -alcohol (the minor enantiomer) increased with the medium concentration therefore, the medium concentration was kept low, optimally to produce the S-enantiomer[82]. The effect of the aeration during cultivation on the enantioselectivity of bakers yeast production of 3-hydroxyesters has also been reported 86 Inducers such as a substrate analog may also induce the desired enzyme to improve the enantioselectivity. 

Figure 15-18. Reduction offluoroketones by Geotrichum candidum IFO 5767 in supercritical C0211181.

The powerful influence of the hydrophobic resin was also demonstrates in the Geotrichum candidum catalyzed reduction of simple aliphatic and aromatic ketones11261. For example, the enantioselectivity of the reduction of6-methylhept-5-en-2-one was improved from 27% ee (R) to 98% ee (S). 

Table 15-15. Synthesis of chiral fluorinated alcohols by the reduction with acetone powder and isolated enzymes of Geotrichum candidum IFO 4597174.

An example of a suitable biocatalyst is Geotrichum candidum, harboring both an oxidizing and a reducing enzyme activity. Table 16.2-14 shows the catalytic performance of Geotrichum candidum towards different substrates12201 when the biocatalyst is incubated for 24 h with 27 mM substrate. Allyl alcohol effectively shifts the stereoselectivity of the reduction. It is presumed to inhibit enzyme(s) that reduce aryl... 

The preparation of optically active (-)-cis- and (-)- r ms-2,4-dimethylcyclohexanones by enantioselective double-bond reduction with B. sulfurescens and the application of these products to the synthesis of cycloheximides has recently been reported93. The same reaction was explored later using Geotrichum candidum for the reduction of 3-carboxy-2-cyclohexenone ester leading to a single optically pure (15,35 )-hydroxy ester. The product of this bioconversion was used in a synthesis of chiral glutamic acid analogs99. 

Enzymes are an increasingly available and important tool in the arsenal of the synthetic chemist. Enzymatic reductions are often straightforward and highly stereoselective. There are now many enzymatic transformations that are compatible with the use of organic solvents.6l5 Other solvents can be used as well, illustrated by the enzyme alcohol dehydrogenase from Geotrichum candidum, which is active in supercritical carbon dioxide.6i6 Prelog studied the reduction of ketones with several enzymatic systems. Reduction of... 

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