TY - JOUR
T1 - Asymmetric synthesis of tert-butyl (3R, 5S) 6-chloro-dihydroxyhexanoate with Lactobacillus kefir
AU - Amidjojo, Maya
AU - Franco-Lara, Ezequiel
AU - Nowak, Alessandro
AU - Link, Hannes
AU - Weuster-Botz, Dirk
N1 - Funding Information:
Acknowledgements The authors are very grateful to Prof. Dr. M. Mueller (University of Freiburg, Germany) for providing us with the dioxohexanoate substrate, the pure intermediate and dihydroxy product for analytical purposes, as well as for many helpful discussions. We would also like to thank Dr. W. Hummel (University of Duesseldorf, Germany) and Dr. T. Daussmann (Juelich Fine Chemicals, Juelich, Germany) for helpful discussions. This work was supported by the Deutsche Bundesstiftung Umwelt (grant no. AZ 13040/03).
PY - 2005/11
Y1 - 2005/11
N2 - An efficient whole cell biotransformation process using Lactobacillus kefir was developed for the asymmetric synthesis of tert-butyl (3R, 5S) 6-chloro-dihydroxyhexanoate, a chiral building block for the HMG-CoA reductase inhibitor. The effects of buffer concentration, temperature, pH and oxygen on the asymmetric reduction were investigated in batch reactions. Improvements in final product concentration and yields of 153% (120 mM) and 79% (0.85 mol/mol) with respect to the batch-process were achieved in an optimised fed-batch process. The pure substrate tert-butyl-6-chloro-3,5-dioxohexanoate was dispersed as microdroplets into the reaction system. This resulted in a space-time yield of 4.7 mmol l-1 h-1. A diastereomeric excess of >99% was measured for (3R, 5S) and (3S, 5S) tert-butyl 6-chloro-dihydroxyhexanoate.
AB - An efficient whole cell biotransformation process using Lactobacillus kefir was developed for the asymmetric synthesis of tert-butyl (3R, 5S) 6-chloro-dihydroxyhexanoate, a chiral building block for the HMG-CoA reductase inhibitor. The effects of buffer concentration, temperature, pH and oxygen on the asymmetric reduction were investigated in batch reactions. Improvements in final product concentration and yields of 153% (120 mM) and 79% (0.85 mol/mol) with respect to the batch-process were achieved in an optimised fed-batch process. The pure substrate tert-butyl-6-chloro-3,5-dioxohexanoate was dispersed as microdroplets into the reaction system. This resulted in a space-time yield of 4.7 mmol l-1 h-1. A diastereomeric excess of >99% was measured for (3R, 5S) and (3S, 5S) tert-butyl 6-chloro-dihydroxyhexanoate.
UR - http://www.scopus.com/inward/record.url?scp=28344457844&partnerID=8YFLogxK
U2 - 10.1007/s00253-005-1921-6
DO - 10.1007/s00253-005-1921-6
M3 - Article
C2 - 15723213
AN - SCOPUS:28344457844
SN - 0175-7598
VL - 69
SP - 9
EP - 15
JO - Applied Microbiology and Biotechnology
JF - Applied Microbiology and Biotechnology
IS - 1
ER -