For TMC 2 optimized synthesis, we used the reaction time
(140 min) and the solvent ratio (4:1) that lead to highest degrees
of TMC 1 quaternization. We obtained a higher degree of substitution
(46.6%) in the absence of O-methylation at C-3 and C-6, as
confirmed by NMR (Fig. 3). Moreover, chain scission was prevented
(size exclusion chromatography data, not shown). This method is
expected to control the DQ without altering the structural properties
of the glucosamine units (Verheul et al., 2008).
In Fig. 3 are presented chemical shifts for TMC 1 and TMC 2. The
signal intensity present in TMC 1 at 3.4 ppm (peak 8) demonstrates
that O-methylation occurred during the reaction. In contrast, spectra
(B) of TMC 2 obtained through the optimized method shows