depend on steric factors alone, but also on electronic issues [293, 296, 416]. Note
that a rigid (E)-C¼C bond or a bulky aromatic system [417] on the 2-substituent led
to an enhanced selectivity of the enzyme as compared to the corresponding saturated analogs. When the configuration of the double bond was Z, a reversal in the
stereochemical preference took place, associated with an overall drop of selectivity.
Additionally, this study shows a positive influence of a biphasic system (using
di-iso-propyl ether or toluene [418] as water-immiscible organic cosolvent) on the
enantioselectivity of the enzyme.
Chiral epoxy alcohols, which are not easily available via the Sharpless procedure
due to lack of a directing hydroxy moiety [419], were successfully resolved with
PPL (Scheme 2.51). Interestingly, the lipase is not deactivated by a possible
reaction with the epoxide moiety [420, 421]. The significant influence of the nature
of the acyl moiety on the selectivity of the resolution – again, long-chain fatty acid
esters gave better results than the corresponding acetate – may be attributed to the
presence of different hydrolytic enzymes present in the crude PPL preparation
[422, 423]. In particular α-chymotrypsin and cholesterol esterase are known to
hydrolyze acetates of alcohols but not their long-chain counterparts. Thus, they are
more likely to be competitors of PPL on short-chain acetates. In order to improve
the modest enantioselectivity of crude PPL for industrial applications, a pure
hydrolase was isolated from crude pancreatin, which gave perfect enantioselectivity
(E > 100) in the presence of dioxane as cosolvent [424].
OH
R
AcO
R
HO
OAc
R
AcO
OAc
buffer
buffer
PPL
PPL
S
R
R
Cosolvent Configuration e.e. [%]
n-C 7 H 15 -
i-Pr 2 O
S
70
(CH 3 ) 2 CH-(CH 2 ) 2 -
i-Pr 2 O
S
72
(E)-n-C 5 H 11 -CH=CHnone
S
84
(E)-n-C 5 H 11 -CH=CHi-Pr 2 O
S
95
(Z)-n-C 5 H 11 -CH=CHi-Pr 2 O
R
53
(E)-(CH 3 ) 2 CH-CH=CHnone
S
90
(E)-(CH 3 ) 2 CH-CH=CHi-Pr 2 O
S
97
(Z)-(CH 3 ) 2 CH-CH=CHi-Pr 2 O
R
15
Scheme 2.50 Desymmetrization of prochiral 1,3-propanediol diesters by procine pancreatic
lipase
90
2 Biocatalytic Applications
that a rigid (E)-C¼C bond or a bulky aromatic system [417] on the 2-substituent led
to an enhanced selectivity of the enzyme as compared to the corresponding saturated analogs. When the configuration of the double bond was Z, a reversal in the
stereochemical preference took place, associated with an overall drop of selectivity.
Additionally, this study shows a positive influence of a biphasic system (using
di-iso-propyl ether or toluene [418] as water-immiscible organic cosolvent) on the
enantioselectivity of the enzyme.
Chiral epoxy alcohols, which are not easily available via the Sharpless procedure
due to lack of a directing hydroxy moiety [419], were successfully resolved with
PPL (Scheme 2.51). Interestingly, the lipase is not deactivated by a possible
reaction with the epoxide moiety [420, 421]. The significant influence of the nature
of the acyl moiety on the selectivity of the resolution – again, long-chain fatty acid
esters gave better results than the corresponding acetate – may be attributed to the
presence of different hydrolytic enzymes present in the crude PPL preparation
[422, 423]. In particular α-chymotrypsin and cholesterol esterase are known to
hydrolyze acetates of alcohols but not their long-chain counterparts. Thus, they are
more likely to be competitors of PPL on short-chain acetates. In order to improve
the modest enantioselectivity of crude PPL for industrial applications, a pure
hydrolase was isolated from crude pancreatin, which gave perfect enantioselectivity
(E > 100) in the presence of dioxane as cosolvent [424].
OH
R
AcO
R
HO
OAc
R
AcO
OAc
buffer
buffer
PPL
PPL
S
R
R
Cosolvent Configuration e.e. [%]
n-C 7 H 15 -
i-Pr 2 O
S
70
(CH 3 ) 2 CH-(CH 2 ) 2 -
i-Pr 2 O
S
72
(E)-n-C 5 H 11 -CH=CHnone
S
84
(E)-n-C 5 H 11 -CH=CHi-Pr 2 O
S
95
(Z)-n-C 5 H 11 -CH=CHi-Pr 2 O
R
53
(E)-(CH 3 ) 2 CH-CH=CHnone
S
90
(E)-(CH 3 ) 2 CH-CH=CHi-Pr 2 O
S
97
(Z)-(CH 3 ) 2 CH-CH=CHi-Pr 2 O
R
15
Scheme 2.50 Desymmetrization of prochiral 1,3-propanediol diesters by procine pancreatic
lipase
90
2 Biocatalytic Applications