Enzym-katalysierte kinetische Racematspaltung von Tramadol-Analoga und deren industrielle Anwendbarkeit
type: CreativeWork
description: The aim of the thesis was the development of new methods for the enzymatic kinetic resolution of tramadol analogues. With these methods it should be possible to synthesize both enantiomers of new analgesics of the tramadol type. In the first part of the thesis tramadol analogues with an aromatic hydroxy group were investigated as substrates in enzymatic kinetic resolutions. It could be demonstrated, that in the lipase catalyzed hydrolysis with o-desmethyltramadol as substrate good selectivities and yields were achieved suitable for the synthesis of both enantiomers in a large scale. This is remarkable because O-desmethyltramadol is member of a large group of biologically active chiral compounds which contains, besides an aromatic hydroxy no other functional groups suitable for a hydrolase catalyzed reaction. The second group of investigated substrates has an additionally secondary hydroxy group in the cyclohexane ring system. Part of the group are biologically active molecules currently investigated by the company Grünenthal, Aachen. It could be demonstrated that these substrates could be subjected not only to the enzymatic hydrolysis but also to enzyme catalyzed transesterification with high selectivities and yields. Especially the enzyme catalyzed hydrolysis of cyclohexanol type of tramadol analogues has proven to be an easy and efficient method for the synthesis of enantiopure molecules, because the separation of the alcohol and the ester was conveniently achieved simply by extraction with variations of the pH value of the solution. Alternatively these enantiopure products could also be synthesized very successfully by transesterfication reactions in organic media. As an important aspect the it could be demonstrated that the enzymatic kinetic resolution allows for attainment of both enantiomers simply by choosing the right enzyme.
abstract: The aim of the thesis was the development of new methods for the enzymatic kinetic resolution of tramadol analogues. With these methods it should be possible to synthesize both enantiomers of new analgesics of the tramadol type. In the first part of the thesis tramadol analogues with an aromatic hydroxy group were investigated as substrates in enzymatic kinetic resolutions. It could be demonstrated, that in the lipase catalyzed hydrolysis with o-desmethyltramadol as substrate good selectivities and yields were achieved suitable for the synthesis of both enantiomers in a large scale. This is remarkable because O-desmethyltramadol is member of a large group of biologically active chiral compounds which contains, besides an aromatic hydroxy no other functional groups suitable for a hydrolase catalyzed reaction. The second group of investigated substrates has an additionally secondary hydroxy group in the cyclohexane ring system. Part of the group are biologically active molecules currently investigated by the company Grünenthal, Aachen. It could be demonstrated that these substrates could be subjected not only to the enzymatic hydrolysis but also to enzyme catalyzed transesterification with high selectivities and yields. Especially the enzyme catalyzed hydrolysis of cyclohexanol type of tramadol analogues has proven to be an easy and efficient method for the synthesis of enantiopure molecules, because the separation of the alcohol and the ester was conveniently achieved simply by extraction with variations of the pH value of the solution. Alternatively these enantiopure products could also be synthesized very successfully by transesterfication reactions in organic media. As an important aspect the it could be demonstrated that the enzymatic kinetic resolution allows for attainment of both enantiomers simply by choosing the right enzyme.
author: Griebel, Carsten
language: ger
keywords: info:eu-repo/classification/ddc/540, Chemie, Tramadol, Enzym, Katalyse, Analgetika
date published: 2003
date modified: 2026-07-30T19:43:10Z
provider: RWTH Aachen University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Publikationsserver der RWTH Aachen University