Industrial Biotransformations

Lipase
Candida antarctica
2
F
1) Reaction conditions
[1]: 0.876 M, 200 g · L –1 [228.24 g · mol –1 ]
T: 0 °C
medium: vinyl acetate in acetonitrile
reaction type: carboxylic ester hydrolysis
catalyst: immobilized enzyme (Novozyme 435)
enzyme: triacylglycerol acylhydrolase
strain: Candida antarctica
CAS (enzyme): [9001–62–1]
2) Remarks
F
● The lipase from Candida antarctica catalyzes the pro-S acetylation of the diol.
● In addition to 74 % of the (S)-monoacetate, 26 % of the diacetate is formed.
● Acetonitrile is selected as solvent since the subsequent iodocyclization is also carried out in
acetonitrile (see product application). Therefore, the reaction solution can be directly transferred
to the chemical step after separating the lipase by filtration. To do so, it is important to
reach a very high conversion, since the racemic diol also reacts in the iodocyclization. With the
diacetate no reaction takes place.
● As acylating agent 1.25 equivalents of vinyl acetate are used.
3) Flow scheme
Not published.
OH
F
(S)-2
EC 3.1.1.3
1 = 2-[2-(2,4-difluoro-phenyl)-allyl]-propane-1,3-diol
2 = acetic acid 4-(2,4-difluoro-phenyl)-2-hydroxymethyl-pent-4-enyl ester
3 = acetic acid 2-acetoxymethyl-4-(2,4-difluoro-phenyl)-pent-4-enyl ester Schering Plough
Fig. 3.1.1.3 – 1
1
OH
+
E
OAc
F
OAc
OH
+
F
F
3
OAc
OAc
297