H. J. Deussen; M. Zundel; M. Valdois; S. V. Lehmann; V. Weil V; C. M. Hjort; P.R. Ostergaard; E. Marcussen; S. Ebdrup.
"Process development on the enantioselective enzymatic hydrolysis of S-ethyl 2-ethoxy-3-(4-hydroxyphenyl)propanoate."
Organic Process Research and Development, 7 (1), 82-88 (2003).
Abstract
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 PPARalpha and -gamma 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).
O. Kirk; M.W. Christensen.
"Lipases from Candida antarctica - unique biocatalysts from a unique origin."
Organic Process Research & Development, 6, 446-451 (2002)
Abstract
The specificity of the A-lipase from Candida antarctica (CALA) has been characterized to further clarify the scope of the biocatalyst. The lipase was foun d to exhibit an almost uniform activity towards various straight-chained primary alcohols and carboxylic acids, only exhibiting a low activity towards very short-chained acids. More interestingly, the enzyme was found to exhibit a high activity towards a surprising diversity of sterically hindered alcohols, including both secondary and tertiary alcohols. These results indicate that CALA can have a unique applicability for the conversion of highly branched substrates where most other lipases fail to display any activity. A new, potentially highly cost-effective, immobilization technology using silica-based granulation has been applied in the immobilization of the B-lipase from the same yeast (CALB). Highly stable particles were obtained with an activity comparable to that of the commercially available immobilized preparations of this enzyme.
T.L. Husum; C.T. Jørgensen; M.W. Christensen; O. Kirk.
"Enzyme Catalysed Synthesis in Ambient Temperature Ionic Liquids"
Biocatalysis and Biotransformation, 19, 331-338 (2001)
Abstract
The activity of three different lipases, a glycosidase and a protease in ionic liquids has been studied. Ambient temperature ionic liquids are a new class of solvents that are nonvolatile and nonflammable and thus an interesting alternative to classical organic solvents. Monitoring the synthesis of a simple ester, all lipases were found to exhibit both excellent activity and stability in the non- polar ionic liquid 1-butyl-3-methylimidazolium hexaflurophosphate ([bmin][PF6], 1). Furthermore, beta - galactosidase from E. coli and the Subtilisin protease Savinase(TM) were both found to exhibit a hydrolytic activity in a 50% aqueous solution of the water-miscible ionic liquid 1-butyl-3-methylimidazolium tetrafluoroborate ([bmin][BF4], 2) comparable to the activity observed in 50% aqueous solutions of ethanol and acetonitrile.
E.M. Anderson; K.M. Larsson; O. Kirk.
"One Biocatalyst - Many Applications: The Use of Candida antarctica B-lipase in Organic Synthesis".
Biocatalysis and Biotransformation, 16, 181-204 (1998)
Abstract
The application of the B-component lipase from the yeast Candida antarctica in organic synthesis is reviewed. This enzyme has been found to be a particularly efficient and robust lipase catalyzing a surprising diversity of reactions including many different regio- and enantio-selective syntheses. Furthermore, the C. antarctica B-lipase is an example of an enzyme for which its specificity has been predicted based on the crystal structure and modeling of the active site region. This prediction is compared to experimental observations and a very close correlation is found