Optically active compounds, microbial

The oxidations accomplished by microorganisms or enzymes excel in regiospecificity, stereospecificity, and enantioselectivity. Although the yields of such oxidations are sometimes fair and even low, optical purity (enantiomeric excess) is usually very high and frequently 100%. The spectrum of microbial and enzymatic oxidations is unbelievably broad many different positions in steroidal rings can be hydroxylated by different microorganisms, and usually, only one diastereomer is formed. From achiral molecules, optically active compounds are generated. 

Resolution of enantiomers, separation of diastereomers, asymmetric synthesis, microbial and enzymatic reactions and synthesis from chiral starting materials are all methods for producing optically active compounds. 

Stereoselective enzymatic hydrolyses of esters represent a further type of biotransformation that has been used for the synthesis of optically active organosilicon compounds. The first example of this particular type of bioconversion is illustrated in Scheme 15. Starting from the racemic (l-acetoxyethyl)silane rac-11, the optically active (l-hydroxyethyl)silane (5)-41 was obtained by a kinetic racemate resolution using porcine liver esterase (PLE E.C. 3.1.1.1) as the biocatalyst7. The silane (5)-41 (isolated with an enantiomeric purity of 60% ee bioconversion not optimized) is the antipode of compound (R)-41 which was obtained by an enantioselective microbial reduction of the acetylsilane 40 (see Scheme 8). 

Intact microbial cells have also been used as biocatalyst for this particular type of bioconversion. Incubation of the racemic 2-acetoxy-l-silacyclohexane rac-(SiS,CR/SiR,CS)-81 with growing cells of the yeast Pichia pijperi (ATCC 20127) yielded the optically active l-silacyclohexan-2-ol (Si/t,CS)-70 (Scheme 16)66,67. Under preparative conditions, this biotransformation product was isolated as an almost enantiomerically pure compound (enantiomeric purity >96% ee) in ca 80% yield [relative to (Si/ ,CS )-81 in the racemic substrate]. 

Enantioselective enzymatic transesterifications have been used as a complementary method to enantioselective enzymatic ester hydrolyses. The first example of this particular type of biotransformation is the synthesis of the optically active 2-acetoxy-l-silacyclohexane (5 )-78 (Scheme 19). This compound was obtained by an enantioselective transesterification of the racemic l-silacyclohexan-2-ol rac-43 with triacetin (acetate source) in isooctane, catalyzed by a crude lipase preparation from Candida cylindracea (CCL, E.C. 3.1.1.3)62. After terminating the reaction at 52% conversion (relative to total amount of substrate rac-43), the product (S)-78 was separated from the nonreacted substrate by column chromatography on silica gel and isolated in 92% yield (relative to total amount of converted rac-43) with an enantiomeric purity of 95% ee. The remaining l-silacyclohexan-2-ol (/ )-43 was obtained in 76% yield (relative to total amount of nonconverted rac-43) with an enantiomeric purity of 96% ee. Repeated recrystallization of (R)-43 led to an improvement of enantiomeric purity by up to >98% ee. Compound (R)-43 has already earlier been prepared by an enantioselective microbial reduction of the l-silacyclohexan-2-one 42 (see Scheme 8)53. The l-silacyclohexan-2-ol (R)-43 is the antipode of compound (.S j-43 which was obtained by a kinetic enzymatic resolution of the racemic 2-acetoxy-l-silacyclohexane rac-78 (see Scheme 15)62. For further enantioselective enzymatic transesterifications of racemic organosilicon substrates, with a carbon atom as the center of chirality, see References 64 and 70-72. 

In 1872 the simplest a,a-disubstituted amino acid (2-aminoisobutyric acid, Aib) was described [3]. In 1908 the first optically active representative of this class of compounds, (/ )-2-ethylala-nine (D-isovaline), was isolated by microbial racemic resolution [4]. Synthetic chemists have therefore been interested in the enantiopure synthesis of a-alkylated a-amino acids for some time. Their powerful methods for the construction of chiral a-amino acids can in some cases also be used for the synthesis of the a-alkylated derivatives which has been the topic of recent reviews [5]. 

In conclusion, enantioselective microbial reductions of silicon and germanium compounds containing an El-C(0)Me (El = Si, Ge) moiety El-CH(OH)Me] proved to be an efficient preparative method for the synthesis of optically active silanes, germanes, and digermanes. Furthermore, the commercially available yeast Saccharomyces cerevisiae (DHW S-3) is considered to be an efficient biocatalyst for this particular type of bioconversion. 

K. N. Raymond, K. Abu-Dari, and S. R. Sofen, Stereochemistry of Microbial Iron Transport Compounds, in Stereochemistry of Optically Active Transition Metal Compounds , Vol. 119, ACS Symposium Series, eds. B. E. Douglas and Y. Saito, 1980, p. 7. 

Another Important attribute of whole cell/enzyme systems is for the production of optlcally-actlve compounds. As early as the 1950s, the synthesis of optically active gamma- and delta-lactones by microbiological reduction was demonstrated (18). Production of optlcally-pure L-glutamate for use in the flavor enhancer MSG by microbial means is another testimonial to this potential of biotechnology. 

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. ... 

Ochratoxin A is a colourless crystalline compound with blue fluorescence under ultraviolet light. It has a weak acidic character, with pfC values of 4.4 (carboxyl group of phenylalanine) and approximately 7.5 (phenolic group). Acid hydrolysis splits ochratoxin A into phenylalanine and ochratoxin alpha, an optically active lactone acid. The lactone ring may be opened by alkali or treatment with some microbial esterases, and this removes toxicity. This reaction is reversible, under acidic conditions (Monad Palmisano, 2004). 

Stereoselective biotransformation with growing cells, resting free or immobilized cells, or isolated enzymes has been demonstrated to be a useful preparative method for the synthesis of centrochiral optically active organosilicon compounds [1-3]. In continuation of our own studies in this field, we have investigated stereoselective microbial transformations of rac-1-(4-fluorophenyl)-l-methyl-l-sila-2-cyclohexanone (rac-1) and rac-(Si5,CR/SiR,C5)-2-acetoxy-l-(4-fluorophenyl)-l-methyl-1-silacyclohexane [rac-(Si5,C/ /Si/f,C5)-3a]. We report here on (i) the synthesis of rac-1 and rac- SiS,CR/SiR,CS)-3a, (ii) the diastereoselective microbial reduction of rac-1 [— (Si5,C/ )-2a, (SiR,C5)-2a], and (iii) the enantioselective microbial hydrolysis of rac-(SiS,CR/SiR,CS)-3a [- (SiR,C5)-2a],... 

The response of the European elm bark beetle to isomers of its pheromone blend was determined with two separate laboratory bioassays and field tests (93, 318). A combination of 3 compounds that act syner-gistically was found (-)-4-methyl-3-heptanol (294a), (-)-a-multistriatin (303a), and (—)-a-cubebene (283) (for formulas, see pp. 48, 49) (93). The absolute configuration of the (—)-a-multistriatin is IS,2R,4S,5R (49) and that of the (—)-4-methyl-3-heptanolis 38,48(147). Both the texam alarm pheromone, (5)-(+)-methyl-3-heptanone, and the alcohol above share 45 stereochemistry. Of interest is the fact that the reduction of decalones by microbial enzymes is usually stereoselective, with optically active alcohols of 5-configurations being obtained (319). 

After the discovery of the antibiotic thienamycin, compounds that contain tiie car-bapenem and penem ring systems have attracted much attention. The importance of stereochemistry of the hydroxyethyl group is demonstrated by the fact that this group must be in the R) configuration for antimicrobial activity to take place. Previously, synthesis of carbapenem and penum compounds have often utilized the optically active P-lactam intermediates [192-194]. Recently, d-(—)-3-hydroxybutyric acid prepared by the microbial hydroxylation of butyric acid has been used in the preparation of p-lactam [195,196]. 

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