Ethyl microbial reduction

Patel and coworkers reported that microbial reduction of ethyl l-benzyl-3-oxopiperidine-4-carboxylate by Candida parapsilosis SC16 347 gave ethyl cis-(3R,4R)-1 -benzyl-3AMiydro-xypiperidine-4/ -carboxylate as the major product in 97.4% diastereomeric excess (de) and 99.8% ee (Figure 7.2), while 99.5% de and 98.2% ee were achieved in the reduction catalyzed by Pichia methanolica SC16 415 [14]. 

Figure 7.2 Synthesis of ethyl cis-(3R,4R) I -henzyl-3I -hydroxypiperidine-4R-carboxylate via microbial reduction...

Guo, Z., Patel, B.P., Corbett, R.M. et al. (2006) Stereospecific microbial reduction of ethyl l-benzyl-3-oxo-piperidine-4-carboxylate. Tetrahedron Asymmetry, 17 (13), 2015-2020. 

This procedure describes an efficient method for the synthesis of >99% enantiomerically pure ethyl glycidate from L-serine. Although preparation of potassium glycidate via cyclization of 3-bromo-2-hydroxypropionic acid,2 and from 3-chloro-2-hydroxypropionic acid (obtained by microbial reduction of chloropyruvic acid)3 was previously reported, the corresponding ethyl ester was never described. An enantioselective synthesis of the 2,3-epoxy acid by oxidation of 2,3-epoxypropanol has also been reported.4... 

D. B. Brzozowski, R. L. Hanson, and L. J. Szarka, Enantioselective microbial reduction of 3,5-dioxo-6-(benzyloxy) hexanoic add, ethyl ester, Enzyme Microb. Technol. 1993, 15, 1014-1021. 

S. Takahashi, M. Wada, M. Kataoka, and S. Shimizu, Synthesis of optically active ethyl 4-chloro-3-hydroxybutanoate by microbial reduction, Appl. Microbiol. Biotechnol. 1999, 53, 847-51. 

Fig. 10. Diversity of microbial reduction of ketopantolactone (a), ketopantoic acid (b), and ethyl 2 -ketopantothenate (c). Symbols A, yeasts O, molds , bacteria , actinomycetes , basidiomycetes...

RN Patel, A Banerjee, CG McNamee, LJ Szarka. Stereoselective microbial reduction of N-(4-(l-oxo-2-chloroacetyl ethyl) phenyl methane sulfonamide. Appl Microbiol Biotechnol 40 241-245, 1993. 

STEREOSPECIFIC MICROBIAL REDUCTION OF ETHYL 1-BENZYL-3-OXO-PIPERIDINE-4-CARBOXYLATE... 

Guo, Z., Chen, Y., Goswami, A., Hanson, R. L., and Patel, R. N. 2006a. Synthesis of ethyl and t-butyl (3R,5S)-dihydroxy-6-benzyloxyhexanoates via diastereo- and enantioselective microbial reduction. Tetrahedron Asymm., 77(10), 1589-1602. 

Fig. 31.23. Synthesis of Ethyl (3S)-4-chloro-3-hydroxybutanoate (ECHB) from Ethyl-4-chloroacetoacetate through whole cell microbial reduction.

FIGURE 16.10 Preparation of the chiral C-13 paclitaxel side-chain synthon. (A) Enantio-selective microbial reduction of 2-keto-3-(Al-benzoylamino)-3-phenyl propionic acid ethyl ester 36. (B) Enantioselective enzymatic hydrolysis of cw-3-(acetyloxy)-4-phenyl-2-azetid-inone 38. 

Ethyl-2-(/J)-hydroxy-2-(T,2, 3. 4 -tetrahydro-T,T.4, 4 -tetramethyl-6 -naphthalenyl) acetate 53 (Figure 16.14) and the corresponding acid 54 were prepared as intermediates in the synthesis of the retinoic acid receptor gamma-specific agonist [86]. Enantioselective microbial reduction of ethyl 2-oxo-2-(T,2, 3. 4 -tetrahydro-T,T,4, 4 -tetramethyl-6-naphthalenyl) acetate 55 to alcohol 53 was carried out using Aureobasidiumpullulans SC 13849 at a 98% yield and with an EE of 96%. At the end of the reaction, hydroxyester 53 was adsorbed onto XAD-16 resin and, after filtration, recovered in 94% yield from the resin with acetonitrile extraction. The recovered (/ )-hydroxyester 53 was treated with Chirazyme L-2 or pig liver esterase to convert it to the corresponding (/ )-hydroxyacid 54 in quantitative yield. The enantioselective microbial reduction of ketoamide 55 to the corresponding (/ )-hydroxyamide 52 by A. pullulans SC 13849 has also been demonstrated [86]. 

Patel RN, Banerjee A, Howell JM, McNamee CG, Brzozowski D, Nanduri V, Thottathil JK, Szarka LJ (1995) Stereoselective Microbial Reduction of 2-Keto-3-(N-benzoylamino)-3-phenyl Propionic Acid Ethyl Ester Synthesis of Taxol Side-Chain Synthon. Ann NY Acad Sci 750 166... 

Microbial reduction of ethyl acetoacetate to ethyl (R)-3-hydroxybutyrate in an ionic liquid containing system. Process Biochem., 44, 316-321. 

Microbial reduction of ethyl l-benzyl-3-oxo-piperidme-4-carboxylate 19 has been accomplished by a selection of microbes after screening of 91 microorpnisms, and the best results were achieved particularly by Candida parapsilosis and Pichia methanolica [23]. 

Scheme 12.10 DKR in the microbial reduction of ethyl 1-benzyl-3-oxo-piperidine-4-carboxylate 19.

Paditaxel, a complex terpene molecule with antimitotic activity (commercialized as Taxol ), is used for various cancer treatments, including ovarian and breast cancer treatments. The isolation of this naturally occurring compound requires the harvesting of a large amount of trees and involves difficult purification. A semisynthetic route has been developed based on the coupling of baccatin III (a diterpenoid that can be isolated from yew leaves) with the chiral side-chain (2R,3S)-N-benzoyl-3-phenylisoserine ethyl ester. The latter could be obtained from the diastereoselective microbial reduction of racemic 2-keto-3-(N-benzoylamino)-3-phenylpropionic acid ethyl ester using whole cells of Hansemda sp. (Figure 13.12). Despite concomitant production of the undesired anti diastereomers (2R,3R)-N-benzoyl-3-phenylisoser-ine ethyl ester and (2S,3S)-N-benzoyl-3-phenylisoserine ethyl ester (up to 20%) due to nonperfect selectivity, the C-13 side-chain synthon required for paclitaxel... 

A mixture of ethyl 3-keto-5-hydroxy 75 (major) and 5-keto-3-hydroxy 76 (minor) was obtained from partial microbial reduction of ketoester 73. Another mixture of ethyl 3-keto-5-hydroxy 75 (minor) and 5-keto-3-hydroxy 76 (major) was obtained from chemical reduction of ketoester 73. These two mixtures were subjected to microbial reduction by Aeinetobacter sp SCI3874 cells for 6 h. The results indicated that the second reduction of the mono-hydroxy compound by SCI3874 cells was quite enantioselective. Reduction of the 3-keto-5-hydroxy 75 provided predominantly the (3R)-hydroxy, while reduction of the 3-hydroxy-5-keto ester 76 provided predominantly the (5S)-hydroxy compound [136]. 

S. Goldberg, Z. Guo, S. Chen, A. Coswami, R.N. Patel, Synthesis of ethyl- (3R,5S)-dihydroxy-6-benzyloxyhexanoates via diastereo-and enantioselective microbial reduction Cloning and expression of ketoreductase lUfiomAcinetobactersp. SC 13874, Enzyme Microb. Technol. 43 (2008) 544-549. 

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