Asymmetric synthesis of tert-butyl (3R, 5S) 6-chloro-dihydroxyhexanoate with Lactobacillus kefir.
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.
Amidjojo
Maya
M
Institute of Biochemical Engineering, Munich University of Technology, Boltzmannstrasse 15, 85748 Garching, Germany.
Franco-Lara
Ezequiel
E
Nowak
Alessandro
A
Link
Hannes
H
Weuster-Botz
Dirk
D
D001709:Biotechnology / Q000379:methods*; D001711:Biotransformation; D002021:Buffers; D002208:Caproates / Q000378:metabolism*; D005285:Fermentation; D006863:Hydrogen-Ion Concentration; D007778:Lactobacillus / Q000378:metabolism*; D010100:Oxygen; D013237:Stereoisomerism; D013696:Temperature
D002021:Buffers; D002208:Caproates; C507922:tert-butyl (3R, 5S) 6-chloro-dihydroxyhexanoate; D010100:Oxygen