Process Development on the Enantioselective Enzymatic Hydrolysis of S-Ethyl 2-Ethoxy-3-(4-hydroxyphenyl)propanoate

A novel biocatalytic approach for the large-scale production of S-2-ethoxy-3-(4-hydroxyphenyl)propanoic acid S -1 from its racemic ethylester rac -2 by enantioselective hydrolysis has been developed. S -1 is an important building block in the synthesis of PPARα and -γ agonists such as Ragaglitazar [...

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Veröffentlicht in:Organic process research & development 2003-01, Vol.7 (1), p.82-88
Hauptverfasser: Deussen, Heinz-Josef, Zundel, Magali, Valdois, Marine, Lehmann, Søren Vig, Weil, Volker, Hjort, Carsten Mailand, Østergaard, Peter Rahbek, Marcussen, Erik, Ebdrup, Søren
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Sprache:eng
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Zusammenfassung:A novel biocatalytic approach for the large-scale production of S-2-ethoxy-3-(4-hydroxyphenyl)propanoic acid S -1 from its racemic ethylester rac -2 by enantioselective hydrolysis has been developed. S -1 is an important building block in the synthesis of PPARα and -γ agonists such as Ragaglitazar [NNC 61-0029 ((−)DRF2725)]. The development history comprises enzyme screening, biocatalyst and process optimization, and scale-up to pilot plant. The project was thereby highly interdisciplinary by combining biotechnology and chemistry technologies. The final process was successfully run on a 44-kg pilot scale in 43−48% yields and with high enantiomeric purities (98.4−99.6% ee).
ISSN:1083-6160
1520-586X
DOI:10.1021/op0256035