Hydrolases Part I: Enzyme Mechanism, Selectivity and Control in the Synthesis of Well-Defined Polymers - Enzymatic Polymerisation - page 65

of glycolide and lactide using immobilized P. cepacia lipase and pointed out the
possibility of a cationic mechanism being operational during the enzymatic poly-
merization [ 138 ].
Despite the fact that glycolic acid has been successfully used as an acyl donor
in esterification reactions with fatty alcohols, there are few reports dealing with
the enzymatic ROP of glycolide [ 139 ] . On the other hand, cyclic diesters based on
ethylene glycol have been polymerized successfully by lipase catalysis and afford
AA-BB-type polyesters [ 140 , 141 ].

3.2 Lipase-Catalyzed Polycondensation Reactions

Polycondensation reactions of AA-BB- and AB-type monomers (Fig. 2 ) using li-
pases have been described in great detail by a number of groups [ 32 - 39 , 41 , 44 , 45 ,
142 - 146 ] , and pioneering work by Baxenden Chemicals showed the feasibility of
performing this process on a large scale [ 142 ] . Polycondensations are equilibrium
reactions requiring removal of the formed condensation product to shift the equilib-
rium to high conversion. The equilibrium conversion of an ester from an alcohol and
an acid is typically 70%, thus, the formed water needs to be removed effectively to
drive the reaction to completion. Since lipases are catalysts, the position of the equi-
librium is not altered, although it has been observed that the equilibrium conversion
of immobilized preparations can be higher than 70% as a result of the altered water
activity when resins are present [ 147 , 148 ] .
Methods to achieve high conversions in (trans)esterifications involve the use of
activated esters such as vinylesters [ 46 , 49 ] (the formed vinyl alcohol tautomerises
into an aldehyde or ketone) or the use of vacuum [ 36 , 37 ] ormolsieves[ 47 ] to
remove the condensation product and thus shift the equilibrium to high conver-
sion. The most frequently applied lipase in polycondensation reactions is CALB.
CALB is well-known for its deep and narrow active site and high degree of (enan-
tio)selectivity (see [ 10 ] for details on the enantioselectivity of CALB) [ 16 , 17 ] .
Although the substrate scope of Novozym 435 is quite broad, phenols [ 149 ]orester
functionalities with a substituent at the

-position [ 128 ] are poorly accepted. On
the other hand, benzylic [ 150 ] or aliphatic alcohols, aliphatic esters and acids, and
even aromatic esters [ 48 ] are excellent substrates that have led to a large variety of
(co)polyesters.
Important advantages of lipases compared to catalysts such as Lewis or Brønsted
acids are the low reaction temperatures, which permit thermally labile monomers to
be applied, and their high regioselectivity, which allows multifunctional monomers
to be directly polymerized in high selectivity and thus avoids the necessity of pro-
tective group chemistry. The use of multifunctional substrates (Fig. 7 ) in particular
has received a lot of attention because the regioselective nature of lipases allows
the preparation of hydroxy- [ 40 , 50 , 51 , 143 , 145 , 151 - 156 ] or carboxylic-acid-
functional [ 146 ] polyesters that have interesting applications as biomedical and
biodegradable materials [ 152 ] . For example, the copolymerization of sorbitol and

α