Charakterisierung und Anwendung eines gelstabilisierten Zweiphasensystems für die asymmetrische Synthese neuartiger Benzoine mit immobilisierter Benzaldehydlyase

The synthesis of pharmaceutically relevant (R)-benzoins catalyzed by the benzaldehyde lyase is almost exclusively described for aqueous monophasic systems. In such systems the number of convertible hydrophobic substrates is limited, the turn over number is partly unsatisfactory and additives which are commonly used for the improvement of the substrate solubility have a negative influence on the enzyme activity and the product quality. This thesis describes the development of a gel-stabilized two-phase system that enabled the application of the recombinantly produced benzaldehyde lyase derived from Pseudomonas fluorescens in organic solvents for the synthesis of novel, strongly hydrophobic (R)-benzoins. The benzaldehyde lyase was homogeneously purified and immobilized into a PVA matrix for the carboligation of hydrophobic, aromatic or heterocyclic aldehydes in n-hexane. The conversion of the different aldehydes was already up to 77% without prior optimization of the system. (R)-benzoins were synthesized with an enantiomeric excess of predominantly >99%. With respect to the (R)-2,2'-furoin synthesis the enzyme productivity was considerably higher with the gel-stabilized system than with an aqueous monophasic system described in the literature. Furthermore the gel-stabilized two-phase system was investigated and optimized for the synthesis of (R)-3,3-furoin whereas the conversion of 3-furaldehyde was increased to 90%. The product extraction could be improved in a specially engineered, continuously operating fluidized-bed reactor whereby the space-time yield was increased and unwanted side reactions were minimized. Furthermore the physico-chemical properties of the system were investigated. The 9% containing PVA matrix was highly compression-proof and elastic. Even the contact of organic solvents did nearly not influence the stability of the PVA immobilizates. Homogeneous partition of the enzyme in the round-shaped immobilizates was proven. Proteins with a molecule mass of more than 154 kDa were completely retained by the matrix. Besides for n-hexane the substrate specific partition coefficient and diffusion were determined for others solvents as well.

Grantor dc:publisher

Publikationsserver der RWTH Aachen University

Year dc:date

2009

Author dc:creator

• Jäntges, Tanja Ilona

Contributors dc:contributor

• Hartmeier, Winfried

• info:eu-repo/classification/ddc/570
• Asymmetrische Synthese
• Immobilisiertes Enzym
• Organisches Lösungsmittel
• Polyvinylalkohol
• Pseudomonas fluorescens
• Benzoin-Aldolase
• Biowissenschaften, Biologie
• Gelstabilisiertes Zweiphasensystem
• Benzaldehydlyase
• (R)-Benzoins
• asymmetrical synthesis
• immobilized enzyme
• organic solvent
• polyvinyl alcohol
• gel-stabilized two-phase system
• benzaldehyde lyase

Statement dc:rights

• info:eu-repo/semantics/openAccess

Language dc:language

ger

Identifier

https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-113669%22

OAI record oai:identifier

https://publications.rwth-aachen.de/oai2d?verb=GetRecord&metadataPrefix=oai_dc&identifier=oai%3Apublications.rwth-aachen.de%3A51368