Pig Liver Esterase and α-Chymotrypsin
Amongst all the esterases, pig liver esterase (PLE) is clearly the champion considering its general versatility. This enzyme is constitutionally complex and consists
of several so-called isoenzymes, which are associated as trimers of three individual
proteins [211]. However, for many applications this crude mixture can be
used without any problems although the isoenzyme subunits often possess similar
(but not identical [212]) stereospecificities [213]. Thus, the selectivity of crude
PLE may vary, depending on the source and the pretreatment of the enzyme
preparation [214]. The biological role of PLE is the hydrolysis of various esters
occurring in the porcine diet, which would explain its exceptionally wide substrate
tolerance. For preparative reactions it is not absolutely necessary to use the
expensive commercially available enzyme preparation because a crude acetone
powder which can easily be prepared from pig liver is a cheap and efficient
alternative [215].
In general, hepatic esterases from related sources such chickens, hamsters,
guinea pigs, or rats were found to be less versatile when compared to PLE. In
certain cases, however, esterases from rabbit [216, 217] and horse liver (HLE)
[218, 219] proved to be useful substitutes for PLE.
Mild Hydrolysis Acetates of primary and secondary alcohols such as cyclopropyl
acetate [220] and methyl or ethyl carboxylates (such as the labile cyclopentadiene
ester [221]) can be selectively hydrolyzed under mild conditions using PLE,
avoiding decomposition reactions which would occur during a chemical hydrolysis
under acid or base catalysis (Scheme 2.21). For example, this strategy has been used
for the final deprotection of the carboxyl moiety of prostaglandin E 1 avoiding the
destruction of the delicate molecule [222, 223].
Regio- and Diastereoselective Hydrolysis Regiospecific hydrolysis of dimethyl
malate at the 1-position could be effected with PLE as catalyst (Scheme 2.22)
[224]. Similarly, hydrolysis of an exo/endo-mixture of diethyl dicarboxylates with a
bicyclo[2.2.1]heptane framework occurred only on the less hindered exo-position
COOEt
COOH
OH
HO
O
COOMe
OH
HO
O
COOH
+
crude PLE/buffer
KOH/EtOH
+ CO 2
buffer
crude PLE
Prostaglandin E 1
Scheme 2.21 Mild ester hydrolysis by porcine liver esterase
2.1 Hydrolytic Reactions
61
Amongst all the esterases, pig liver esterase (PLE) is clearly the champion considering its general versatility. This enzyme is constitutionally complex and consists
of several so-called isoenzymes, which are associated as trimers of three individual
proteins [211]. However, for many applications this crude mixture can be
used without any problems although the isoenzyme subunits often possess similar
(but not identical [212]) stereospecificities [213]. Thus, the selectivity of crude
PLE may vary, depending on the source and the pretreatment of the enzyme
preparation [214]. The biological role of PLE is the hydrolysis of various esters
occurring in the porcine diet, which would explain its exceptionally wide substrate
tolerance. For preparative reactions it is not absolutely necessary to use the
expensive commercially available enzyme preparation because a crude acetone
powder which can easily be prepared from pig liver is a cheap and efficient
alternative [215].
In general, hepatic esterases from related sources such chickens, hamsters,
guinea pigs, or rats were found to be less versatile when compared to PLE. In
certain cases, however, esterases from rabbit [216, 217] and horse liver (HLE)
[218, 219] proved to be useful substitutes for PLE.
Mild Hydrolysis Acetates of primary and secondary alcohols such as cyclopropyl
acetate [220] and methyl or ethyl carboxylates (such as the labile cyclopentadiene
ester [221]) can be selectively hydrolyzed under mild conditions using PLE,
avoiding decomposition reactions which would occur during a chemical hydrolysis
under acid or base catalysis (Scheme 2.21). For example, this strategy has been used
for the final deprotection of the carboxyl moiety of prostaglandin E 1 avoiding the
destruction of the delicate molecule [222, 223].
Regio- and Diastereoselective Hydrolysis Regiospecific hydrolysis of dimethyl
malate at the 1-position could be effected with PLE as catalyst (Scheme 2.22)
[224]. Similarly, hydrolysis of an exo/endo-mixture of diethyl dicarboxylates with a
bicyclo[2.2.1]heptane framework occurred only on the less hindered exo-position
COOEt
COOH
OH
HO
O
COOMe
OH
HO
O
COOH
+
crude PLE/buffer
KOH/EtOH
+ CO 2
buffer
crude PLE
Prostaglandin E 1
Scheme 2.21 Mild ester hydrolysis by porcine liver esterase
2.1 Hydrolytic Reactions
61