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210 9 Stereoselective Hydrolase-Catalyzed Processes in Continuous-Flow Mode

Water-wet permeable
biocatalyst layer

Aqueous
stream

Biocatalyst retaining, Organic
organic permeable stream
skin layer

S (+ S′)
S′ Racemization
in organic in organic
phase phase

Buffer P
in buffer

S (+ S′)
in organic phase
Figure 9.4 Kinetic resolution with a hollow fiber membrane bioreactor.

The hollow fiber MBR proved to be a suitable system to perform the lipase-
catalyzed KR of various racemic esters of naproxen. (S)-Naproxen [(S)-15]and the
unreacted ester were simultaneously separated (Table 9.4, entry 4) [93]. As much
as 90% ee of (S)-15 was obtained with CrL retained by a polyamide membrane.
A simplified MBR [94] – a laboratory scale CSTR with CrL immobilized on
moderate polar support and a dialysis membrane tube forming a continuous-flow
loop for extracting the product – has been applied for the KR of the racemic
naproxen methyl ester to yield (S)-15 with >90% ee and overall conversion of 30%.
The system shown in Figure 9.4 was claimed to perform DKR by combining
a lipase-catalyzed hydrolysis of racemic naproxen ethyl ester to (S)-naproxen with
racemization of the unreacted (R)-ester in an undefined way and followed by
recycling [95].