Ethyl -2-hydroxy-4-phenylbutyrate

Comparison of Four Technical Syntheses of Ethyl (/ )-2-Hydroxy-4-Phenylbutyrate... 

Scheme 5.1 Four synthetic routes via A-via D to ethyl (R)-2-hydroxy-4-phenylbutyrate (HPB-Ester) according to Blaser eta/. (Figure 3 in reference [10]). In each route, one reaction is a reduction step which is performed using biochemical (A and B) and chemical (C and D) methods, respectively.

Blaser, H.-U., Eissen, M., Fauquex, P.R et al. (2003) Comparison of Four Technical Syntheses of Ethyl (R)-2-Hydroxy-4-Phenylbutyrate. In Earge-Scale Asymmetric Catalysis (eds H.-U. Blaser E. Schmidt), pp. 91-104. WUey-VCH, Weinheim. 

Some developments have been carried out for the enantioselective synthesis of biologically active compounds. One such example is the synthesis of ethyl (R)-2-hydroxy-4-phenylbutyrate, an important intermediate for the angiotensinconverting enzyme (ACE) inhibitor benazepril, or for coenzyme A, using the NORPHOS ligand (Scheme 33.9) [21]. 

The asymmetric syntheses of various chiral compounds have already been compared with regard to their applicability on a technical scale. For example, Blaser and coworkers compared four technically feasible routes (A-D) for the large scale preparation of the chiral building block ethyl (R)-2-hydroxy-4-phenylbutyrate (10) (Scheme 4.13) [53]. The stereogenic centre is introduced via enantioselective reduction, either via biocatalytic or nonenzymatic methods. 

Fig. 1 Structures of ethyl (R)-2-hydroxy-4-phenylbutyrate and of selected ACE inhibitors.

A further example, the preparation of ethyl 3-hydroxy-3-phenylbutyrate from acetophenone, ethyl bromoacetate, and zinc has been described by Lindenbaum 220... 

Chen, Y., Lin, H, Xu, X Xia, S., and Wang, L. (2008) Preparation the key intermediate of angiotensin-converting enzyme (ACE) inhibitors high enantioselective production of ethyl (R)-2-hydroxy-4-phenylbutyrate with Candida boidinii C10C21. Adv. Synth. Catal., 350 (3), 426- 30. 

Wu, X., Wang, Y, (u, ( Chen, C Liu, N and Chen, Y. (2009) Enantioselective synthesis of ethyl (S)-2-hydroxy-4-phenylbutyrate by recombinant diketoreductase. Tetrahedron Asymmetry,... 

Fig. 10.19 Chromatogram of organic acids extracted using ethyl acetate from the urine of a patient with 3-hydroxy-3-methylglutaric aciduria and separated as their trimethylsilyl derivatives on 5 per cent SE 52 on Chromosorb W (AW-DMCS, 100-120 mesh) using temperature programming from 75°C to 220°C at 2°C min with initial and final isothermal delays of 10 min. Peak identifications are 1, 3-hydroxyisovalerate 2, hydroxycaproate isomer 3, glutarate 4, 3-methylglutarate 5 and 6, 3-methyl-glutaconate peaks 7, adipate 8, 4-phenylbutyrate (internal standard) 9, 3-hydroxy-3-methylglutarate 10, ascorbate. (Redrawn with modifications from Duran ct. a/., 1978)...

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