Page 242 - Cascade_Biocatalysis_Integrating_Stereoselective_and_Environmentally_Friendly_Reactions

218 9 Stereoselective Hydrolase-Catalyzed Processes in Continuous-Flow Mode

MeO
NBoc
MeO
n
AcO
(S)-22a (n = 1)
MeO (R)-22b (n = 2)
AcO-CH=CH
2
CaLB rac-22c (n = 3)
NBoc Toluene
MeO
+
n MeO
HO
21a (n = 1) n = 1: E >200 NBoc
MeO

21b (n = 2) n = 2: E = 21

21c (n = 3) n = 3: E = 1 HO n
(R)-22a (n = 1)
(S)-22b (n = 2)
rac-22c (n = 3)
Figure 9.8 Hydrolase-catalyzed kinetic resolution of primary alcohols 21a–c by acylation in
continuous-flow PBR.
Numerous hydrolase-catalyzed KRs of various secondary alcohols were per-
formed in continuous-flow mode (Figure 9.8 and Table 9.6). The bioimprinting
effect in sol–gel immobilization of various lipases (Lipase AK, Lipase PS, CaLB,
and CrL) was studied [116]. The performance of the immobilized biocatalysts were
characterized by enantiomer selective acylation of various racemic secondary alco-
hols in two different multisubstrate systems (mix A: rac-23a,c–e and mix B: rac-23b
and rac-23i) in batch and continuous-flow mode. The synthetic usefulness of the
best biocatalysts was demonstrated by the KR of racemic 1-(thiophen-2-yl)ethanol
(rac-23j) in batch and continuous-flow systems [116].
A detailed kinetic modeling and reactor parameter study was carried out on KR of
1-methoxy-2-propanol (rac-23f) with vinyl acetate using a PBR filled with immobi-
lized CaLB [117]. The model simulation was validated in a fully automated modular
miniplant and was shown to be capable of predicting the key parameters of a KRsuch
as enantiomeric excess and the extent of conversion at a given superficial velocity.
A study of the continuous-flow KRs of 1-phenylpropan-2-ol, 1-cyclohexylethanol,
and 1-phenylethanol (rac-23g,h,i respectively) was performed in small stainless
steel PBRs filled with different commercial lipase preparations [118]. Comparison
of the continuous-flow and batch mode (shaken flask) KRs mostly indicated similar
enantiomer selectivities (E) but higher productivities (r) in the corresponding
continuous-flow reaction.
Another study of continuous-flow KRs of rac-23h and rac-23i in PBR with
PfL entrapped in sol–gel matrices formed from binary silane precursor systems
of disubstituted diethoxysilanes and tetraethoxysilane indicated the operational
stability of the sol–gel PfL in such applications [119].
Thoroughly studied continuous-flow KR was the lipase-catalyzed acylation of
1-phenylethanol rac-23i in various continuous-flow systems [114, 116, 118–123].