Lipase-catalyzed kinetic resolution of branched chain fatty acids and their esters : a study towards the production of enantiopure 4-methyloctanoic acid = Lipase-gekatalyseerde kinetische resolutie van vertakte vetzuren en hun esters : een studie naar de productie van enantiomeer zuiver 4-methyloctaanzuur

N.W.J.T. Heinsman

Research output: Thesisinternal PhD, WU

Abstract

<p>Flavors and fragrances make an important contribution to the taste and smell of all kinds of food products both as natural occurring components and as additional flavors or fragrances. One of these flavor components is 4-methyloctanoic acid (4-MOA). This branched chain fatty acid contributes to the characteristic smell and taste of mutton and sheep's cheese. The enantiomers of 4-MOA have a different smell and taste; it is therefore a challenge to separate both stereoisomers. One possible way of separation, which is designated as food-grade, is enzyme catalyzed kinetic resolution. Since the chiral center is positioned at theγ-carbon atom, a low enantioselectivity was expected. Therefore, sequential kinetic resolution (esterification followed by hydrolysis) was investigated. To find a suitable enzyme to catalyze these reactions, a group of 25 hydrolases was screened in the transesterification of 4-methyloctanoic acid methyl ester, resulting in the selection of Novozym 435 <sup>®</sup> .</p><p>This enzyme was used to esterify 4-MOA with polyethylene glycol (PEG, food grade). Unfortunately PEG appeared not to be suitable since no stable two-phase system could be formed, which was necessary for the continuous production of enantiomerically pure 4-MOA in a diffusion membrane reactor. Therefore, PEG was replaced by ethanol (food grade) in the esterification of 4-MOA. In this reaction, part of the substrate appeared to sorb into the polymer matrix of the immobilization material of Novozym 435 <sup>®</sup> affecting the enantiomeric ratio estimation. Therefore correction for sorption was needed. The enantioselectivity of the enzyme was dependent on the alcohol concentration used, both for esterification (optimum <em>E</em> = 57 ± 11, obtained for the ratio 1:8 (mol fatty acid: mol EtOH)) and for hydrolysis (optimum <em>E</em> =12 ± 1, in the presence of 20% (v/v) EtOH). When combining these results, sequential kinetic resolution of 4-methyloctanoic acid will result in an enantiomeric ratio of approximately 350.</p><p>Since integration of esterification and product separation resulted in a low enantiomeric ratio ( <em>E</em> = 15) in comparison with the batch reaction ( <em>E</em> = 57), and simulation and measurements showed no improvement of the <em>ee</em><sub>p</sub> , the batch reaction is recommended to obtain enantiopure 4-methyloctanoic acid.</p>
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
Supervisors/Advisors
  • van 't Riet, K., Promotor
  • de Groot, Æ., Promotor, External person
  • van der Padt, A., Promotor
  • Franssen, M.C.R., Promotor, External person
Award date25 Oct 2000
Place of PublicationS.l.
Publisher
Print ISBNs9789058082558
Publication statusPublished - 2000

Keywords

  • synthesis
  • enantiomers
  • branched chain fatty acids

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