480
3
Chemical Glycosylation Reactions
⊡ Scheme 17
(continued)
having O-acetyl groups as temporary protection for chain extension and one per-O-benzylated
O-mannopyranosyl trichloroacetimidate (16j) for chain termination a tetrasaccharide 16k was
obtained which was cleaved from the resin (→ 16l) by cross metathesis. Transformation into
a trichloroacetimidate 16m and glycosylation of a pseudodisaccharide led after deprotection
to the target molecule 16n.
For the real-time monitoring of the glycosylation result by the Ito group sensitive color tests
were introduced with p-nitrobenzylpyridine (PNBP), reacting with chloroacetyl (CAc) as the
temporary protecting group under red color formation, and with cyanuric chloride-Disperse
Red conjugate, which readily reacts with hydroxy or amino groups to give a red color on the
resin [115]. This way, as shown in > Scheme 17, the repeating unit 17e of the immuno-active
oligosaccharide schizophyllan was synthesized based on a partly CAc-protected O-glucosyl
trichloroacetimidate donor 17f with 17a as starting material and 17b to 17d as intermediates;
the presence of the CAc groups could be readily monitored with PNBP and the presence or
absence of hydroxy groups was monitored by the Disperse-Red method. As a linker to piperazine-modified TentaGel, a 2-nitrophenyloxyacetyl group [99] was employed that can be readily cleaved under transesterification conditions. This led also to loss of other ester protecting
groups furnishing the target molecule 17f in very good overall yield.
The synthesis of oligosaccharides on soluble supports has been further investigated as well.
Particularly worth mentioning is the synthesis of heparin-like oligosaccharides on polyethylene glycol ω-monomethyl ether (MPEG) resin with a succinoyl ester linker and O-glycosyl trichloroacetimidates as glycosyl donors [116,117]. A typical example is shown in
> Scheme 18 [117]. After the glycosylation steps of 18a with polymer bound 18b and 18c
with 18d, respectively, catalyzed by TMSOTf, a capping step was included in which unreacted
MPEG-bound acceptor was captured onto the solid-phase of succinate-functionalized Merri-
3
Chemical Glycosylation Reactions
⊡ Scheme 17
(continued)
having O-acetyl groups as temporary protection for chain extension and one per-O-benzylated
O-mannopyranosyl trichloroacetimidate (16j) for chain termination a tetrasaccharide 16k was
obtained which was cleaved from the resin (→ 16l) by cross metathesis. Transformation into
a trichloroacetimidate 16m and glycosylation of a pseudodisaccharide led after deprotection
to the target molecule 16n.
For the real-time monitoring of the glycosylation result by the Ito group sensitive color tests
were introduced with p-nitrobenzylpyridine (PNBP), reacting with chloroacetyl (CAc) as the
temporary protecting group under red color formation, and with cyanuric chloride-Disperse
Red conjugate, which readily reacts with hydroxy or amino groups to give a red color on the
resin [115]. This way, as shown in > Scheme 17, the repeating unit 17e of the immuno-active
oligosaccharide schizophyllan was synthesized based on a partly CAc-protected O-glucosyl
trichloroacetimidate donor 17f with 17a as starting material and 17b to 17d as intermediates;
the presence of the CAc groups could be readily monitored with PNBP and the presence or
absence of hydroxy groups was monitored by the Disperse-Red method. As a linker to piperazine-modified TentaGel, a 2-nitrophenyloxyacetyl group [99] was employed that can be readily cleaved under transesterification conditions. This led also to loss of other ester protecting
groups furnishing the target molecule 17f in very good overall yield.
The synthesis of oligosaccharides on soluble supports has been further investigated as well.
Particularly worth mentioning is the synthesis of heparin-like oligosaccharides on polyethylene glycol ω-monomethyl ether (MPEG) resin with a succinoyl ester linker and O-glycosyl trichloroacetimidates as glycosyl donors [116,117]. A typical example is shown in
> Scheme 18 [117]. After the glycosylation steps of 18a with polymer bound 18b and 18c
with 18d, respectively, catalyzed by TMSOTf, a capping step was included in which unreacted
MPEG-bound acceptor was captured onto the solid-phase of succinate-functionalized Merri-