Page 22 - Catalysts for Fine Chemical Synthesis Vol 1 - Robert & Poignant

the integration of biotransformations into catalyst 5

Pseudomonas putida esterase or pig liver esterase, (ple) or proteases (e.g. sub-
tilisin) are employed in the reactions described in equation (1), while lipases (e.g.
Candida antarctica lipase) are more often used for transformations illustrated in

Enz, H 2 O
H 2 O + R*CO 2 Me R*CO 2 H + MeOH (1)

Enz, H 2 O
H 2 O + R*OCOMe R*OH + MeCO 2 H (2)

Enz, H 2 O
H 2 O + R 1 CO 2 R 2 * R 1 CO 2 H + R 2 *OH (3)
R* ˆ chiral unit; Enz ˆ esterase or lipase

Figure 1.1 Generalized scheme illustrating the hydrolysis of esters using enzymes.

equations (2) and (3). Obviously in order to obtain optically active acid and/or
alcohol the reaction is not taken to completion but stopped at about the halfway
stage. The enantiomer ratio E [7] indicates the selectivity of the enzyme catalysed
reaction. E values > 100 indicate highly enantioselective biotransformations.
[9]
Typical resolutions are illustrated in Schemes 1 [8] and 2 . There have been

i
R 1 CH(Me)CO 2 Me R 1 CH(Me)CO 2 H + MeOH
(S )-stereoisomer E > 500

Scheme 1: Reagents and conditions: i) Ps. putida esterase H 2 O:

i
F 5 C 6 −CH(OCOMe)CN F 5 C 6 −CH(OH)CN+MeCO 2 H
(S)-stereoisomer E > 200

Scheme 2: Reagents and conditions: i) lipase LIP, H 2 O, buffer pH 5±6.

models postulated for many of the popular enzymes (pig liver esterase, Candida
rugosa lipase) in order better to predict the preferred substrate in a racemic
mixture [10] .
The ability of hydrolases to hydrolyse esters derived from primary alcohols
in the presence of esters derived from secondary alcohols has been recognized
(Scheme 3) [11] .