Chemistry Reference
In-Depth Information
Scheme 8.3
Grafting procedure on the
N
-acetylglucosamine primary hydroxyl groups performed
in aprotic polar solvents employing HA-TBA. In this case, opportune agent is employed to activate
the hydroxyl group, and then an amino-terminated polymer is employed for coupling. (
a
) Activa-
tion of the
N
-acetylglucosamino hydroxyl group in water by using cyanogen bromide [
26
].
(
b
) Activation of the
N
-acetylglucosamino hydroxyl group in DMSO using Bis(4-nitrophenyl)
carbonate condensing agents [
27
,
28
](R
¼
polymeric chain)
An alternative functionalization strategy consists in the activation of HA pri-
mary hydroxyl groups by using a proper condensing agent. This activation can be
performed in aqueous or organic medium, and it has often the advantage of high
chemical selectivity and efficiency. Moreover, in some cases, it is possible to isolate
the activated HA intermediate that can be employed, on the occurrence, with the
opportune polymer to perform the coupling reaction. As an example, Mlˇochov´
described the activation of the
N
-acetylglucosamino hydroxyl group in water by
using cyanogen bromide; the intermediate HA-cyanate reacts efficiently with an
amino-substituted polymer forming a stable carbamate linkage (Scheme
8.3
a) [
26
].
A similar carbamate linkage can be also formed in a polar aprotic solvent
employing as HA activator a p-nitrophenyl carbonate condensing agent such as
bis(4-nitrophenyl) carbonate (4-NPBC) or chloro-4-nitrophenylcarbonate. The acti-
vation strategy is fast and quantitative and allows grafting procedures with amino-
terminated polymers (see Scheme
8.3
b) [
27
,
28
].
8.2.2 Grafting on HA Carboxyl Groups
Several chemical procedures performed with condensing agents reactive toward
glucuronic carboxyl groups can be performed in water. To avoid the employ of
organic solvents is a good strategy for an easier industrial manufacturing and
scaling-up of all pharmaceutical polymers if higher costs and risks linked to the
treatment of organic wastes are considered; however, when water solubility of
grafting molecules (polymers, active agents, etc.) is poor, the use of organic
solvents cannot be avoided. Water-soluble carbodiimides,
in pH-controlled
