G. Hedstrom et al., ENANTIOSELECTIVE SYNTHESIS OF IBUPROFEN ESTERS IN AOT ISOOCTANE MICROEMULSIONS BY CANDIDA-CYLINDRACEA LIPASE, Biotechnology and bioengineering, 42(5), 1993, pp. 618-624
The enantioselective esterification of racemic ibuprofen, catalyzed by
a Candida cylindracea lipase, was studied in a water-in-oil microemul
sion (AOT/isooctane). By using n-propanol as the alcohol, an optimal w
0 ([H2O]/[AOT] ratio) of 12 was found for the synthesis of n-propyl-ib
uprofenate at room temperature. The lipase showed high preference for
the S(+)-enantiomer of ibuprofen, which was esterified to the correspo
nding S(+)-ibuprofen ester. The R(-)-ibuprofen remained unesterified i
n the microemulsion. The calculated enantioselectivity value (E) for S
-ibuprofen ester was greater than 150 (conversion 0.32). The enzyme ac
tivities of n-alcohols with different chain lengths (3-12) were compar
ed, and it appeared that short- (propanol and butanol) and long-chaine
d (decanol and dodecanol) alcohols were better substrates than the int
ermediate ones (pentanol, hexanol, and octanol). However, unlike secon
dary and tertiary alcohols, all of the tested primary alcohols were su
bstrates for the lipase. The reversible reaction (i.e., the hydrolysis
of racemic ibuprofen ester in the microemulsion) was also carried out
enantioselectively by the enzyme. Only the S form of the ester was hy
drolyzed to the corresponding S-ibuprofen. The reaction yield was, how
ever, only about 4% after 10 days of reaction. The corresponding yield
for the esterification of ibuprofen was about 35% (10 days). The high
enantioselectivity displayed by the lipase in the microemulsion syste
m was seen neither in a similar esterification reaction in a pure orga
nic solvent system (isooctane) nor in the hydrolysis reaction in an aq
ueous system (buffer). The E value for S-ibuprofen ester in the isooct
ane system was 3.0 (conversion 0.41), and only 1.3 for S-ibuprofen in
the hydrolysis reaction (conversion 0.32). The differences in enantios
electivity for the lipase in various systems are likely due to interfa
cial phenomena. In the microemulsion system, the water in which the en
zyme is dissolved is separated from the solvent by a layer of surfacta
nt molecules, thus creating an interface with a relatively large area,
Such interfaces are not present in the pure organic solvent systems (
no surfactant) nor in aqueous systems. (C) 1993 John Wiley & Sons, Inc
.