Industrial Biotransformations

Lipase
Pseudomonas cepacia
2
F
1 = [4-[4a,6b(E)]]-6-[4,4-bis(4-fluorophenyl])-
3-(1-methyl-1H-tetrazol-5-yl)-1,3-butadienyl]- tetrahydro-4-hydroxy-2H-pyran-2-one
2 = acetate of 1
Fig. 3.1.1.3 – 1
1) Reaction conditions
[1]: 0.009 M, 4 g · L –1 [438.43 g · mol –1 ]
T: 37 °C
medium: toluene
reaction type: acetylation
catalyst: immobilized enzyme
enzyme: triacylglycerol acylhydrolase (triacylglycerol lipase)
strain: Pseudomonas cepacia
CAS (enzyme): [9001–62–1]
2) Remarks
F
N N
N N
(R,S)-1
OH
O
O
E (R)-(+)-1
● The lipase is immobilized on a polypropylene support (Accurel PP).
● The reaction suspension additionally contains 2 % (v/v) isopropenyl acetate, 0.05 % distilled
water and 1 % (w/v) lipase (Amano PS-30).
● Isopropenyl acetate is used as acyl donor, since here acetone is produced. If vinyl acetate is
applied as acyl donor then acetaldehyde is formed, which is much more incompatible with
lipases than acetone.
● Immobilized lipase is reused for 5 times in a repetitive batch mode.
+
O
-
HO
O
EC 3.1.1.3
Bristol-Myers Squibb
● The (S)-acetate can be hydrolyzed in a subsequent reaction by the same lipase in an aqueous/
organic two-phase system. The cleaved lactone is resynthesized using pivaloyl chloride.
F
F
F
N N
N N
F
+
N N
N N
(S)-(-)-2
OH
O
OAc
O
O
O
281