Ethyl 2-chloro-3-oxobutanoate

Two interesting yeast carbonyl reductases, one from Candida magnoliae (CMCR) [33,54] and the other from Sporobolomyces salmonicolor (SSCR) [55], were found to catalyze the reduction of ethyl 4-chloro-3-oxobutanoate to give ethyl (5)-4-chloro-3-hydroxybutanoate, a useful chiral building block. In an effort to search for carbonyl reductases with anti-Prelog enantioselectivity, the activity and enantioselectivity of CMCR and SSCR have been evaluated toward the reduction of various ketones, including a- and /3-ketoesters, and their application potential in the synthesis of pharmaceutically important chiral alcohol intermediates have been explored [56-58]. 

Wada, M., Kataoka, M., Kawabata, H. et al. (1998) Purification and characterization of NADPH-dependent carbonyl reductase, involved in stereoselective reduction of ethyl 4-chloro-3-oxobutanoate, from Candida magnoliae. Bioscience Biotechnology and Biochemistry, 62 (2), 280-285. 

M. Wada, K. Kita, H. Yanase, and S. Shimizu, Stereoselective reduction of of ethyl 4-chloro-3-oxobutanoate by Escherichia coli transformant cells coexpressing the aldehyde reductase and glucose dehydrogenase genes, Appl. Microbiol. Biotechnol. 1999, 53, 486-490. 

CR carbonyl reductase GDH glucose dehydrogenase COBE ethyl 4-chloro-3-oxobutanoate BA butyl acetate. 

Organisms Lactobacillus kefir DSM 20587, Saccharomyces cerevisiae, Candida magnoliae, Bacillus megaterium, Thermoanaerobium brockii, Clostridium beijerinckii, Thermoanaerobacter ethanolicus, Rhodococcus ruber DSM 44541. Solvents ace = acetone iPr = i-PrOH. Substrates WM Wieland-Miescher ketone 4-Me-HP 4-methyl Hajos-Parrish ketone COBE ethyl 4-chloro-3-oxobutanoate. 

Wada M, Kawabata H et al (1999) Occurrence of multiple ethyl 4-chloro-3-oxobutanoate-reducing enzymes in Candida magnoliae. J Biosci Bioeng 87 144-148... 

Shimizu, S., Kataoka, M., Katoh, M., Morikawa, T., Miyoshi, T., and Yamada, H. 1990a. Stereoselective reduction of ethyl 4-chloro-3-oxobutanoate by a microbial aldehyde reductase in an organic solvent-water diphasic system. Appl. Environ. Microbiol, 56, 2374-2377. 

Cyclopropyl isocyanates react effectively with various nucleophilic reagents. Ammonia and amines yield urea derivatives, " alcohols and phenols afford carbama-tg5,i5 5,164,181,184,185 )V )y-dimethylhydrazine gives a semicarbazide derivative, whereas cyclo-propylammonium chlorides are obtained in refluxing hydrochloric acid. The yields are usually very good. When more highly functionalized nucleophiles are employed, such as the enolate from ethyl 4-chloro-3-oxobutanoate, more complex molecules can be obtained, e.g. the formation of furanone derivative 15. ... 

Another example is the use of heat treatment as a supplement to the screening process. The enantioselectivity of the reduction of ethyl 4-chloro-3-oxobutanoate by Candida magnoliae was improved from 96.6% ee (S) using untreated cells to 99% ee (S) with heat treated cells [67L... 

One of the most studies a-chloroketones is ethyl 4-chloro-3-oxobutanoate. (Rj- and (S -enantiomers of the corresponding alcohol were produced by various micro-... 

Table 15-17. Comparison of various microorganisms for the reduction of ethyl 4-chloro-3-oxobutanoate.

Figure 16.2-49. Asymmetric reduction of ethyl-4-chloro-3-oxobutanoate catalyzed by an alcohol dehydrogenase (ADH) in recombinant E. coli. The necessary reduction equivalents were derived from the oxidation of isopropanol with the same enzyme.

Initially the substance known as muscimol was also called pantherine 38,53) (/8-toxin, pyroibotenic acid, and agarine as well). Later, Onda proposed that pantherine, isolated from A. pantherina, might be represented by a peptide structure [see Ref. 49 in Eugster (5)]. More recently, Onda identified pantherine as 5-aminomethyl-3-hydroxyisoxazole, the structure already attributed to muscimol, by means of spectroscopic experiments and a chemical correlation with synthetic compounds 54) (Scheme 11). In these studies pantherine was converted to acetoxy-pyrrolidone, and the product was compared with that obtained synthetically from ethyl 4-chloro-3-oxobutanoate. Additionally, 5-... 

The Mannich reaction and its variants have been reviewed, mainly focussing on asymmetric catalysis thereof. Catalytic, enantioselective, vinylogous Mannich reactions have also been reviewed, covering both direct and silyl dienolate methods. Another review surveys Mannich-type reactions of nitrones, oximes, and hydrazones. A pyrrolidine-thiourea-tertiary amine catalyses asymmetric Mannich reaction of N-Boc-imines (e.g. Ph-Ch=N-Boc) with ethyl-4-chloro-3-oxobutanoate to give highly functionalized product (16). Addition of triethylamine leads to one-pot intramolecular cyclization to give an 0-ethyl tetronic acid derivative (17). ... 

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