498
3
Chemical Glycosylation Reactions
5.5 Cell Wall Constituents
Bacterial cell wall peptidoglycan is known as a strong immunopotentiator which induces various mediators such as cytokines, prostaglandins, platelet activation factor, and NO, thus stimulating the immune system [206]. The receptor for peptidoglycans was shown to be TLR2 [207],
the same as for lipoteichoic acids (LTAs) and lipoproteins. Therefore, the synthesis of peptidoglycan fragments is of continuing interest. Recently up to an octasaccharide fragment
was obtained as shown in > Scheme 32 [208,209]. Starting material 32a was transformed
into donor 32b and acceptor 32c based on the temporary protection at O-1 with allyl and at
O-4 with benzylidene. Glycosylation afforded tetrasaccharide 32d which by similar transformation to 32e and 32f led to octasaccharide 32g which could be deprotected to yield target
molecule 32h. This procedure of chain extension could be even extended to the hexadecasaccharide, however the Troc deprotection of this compound failed so far. To the octasaccharide 32h also small peptides were attached via the lactate residue and the biological activity of
the derived compounds was tested.
Many bacterial and fungal cell walls contain homo- and heteroglycans. The synthesis of
fragments of these cell wall constituents has gained increasing interest in the last years. The
Manα(1–3)Manα(1–2)Manα(1–6)Manα(1–2)Man heptasaccharide obtained by mild acetolysis from C. glabrata IFO 0622 has been successfully synthesized by Kong et al. [210]; they
synthesized also a related sulfated pentasaccharide [211]. Also mannan repeating units of
Trichophytan mentagrophytes, T. rubrum [212], Saccharomyces cerevisiae X 2180–1A [213],
and Candida kefyr IFO 0586 [214] have been prepared. Another important class of glycans
are β(1–3)- and β(1–6)-linked glucans which are frequently branched. Glucans consisting
of β(1–3)-linked glucose residues having β(1–6)-linked branches have been found in many
plants and fungi [215,216]. Since these glucans show antitumor activity, the synthesis of at
least minimal structural units for biological activity studies has gained great interest [217].
Recently, several successful syntheses of such molecules have been reported mainly by
Kong et al. [218,219,220,221,222,223]. Also a 2-branched β(1–3)-glucan was found and
dimers of the trisaccharide repeating unit were prepared [224]. 3-Branched β(1–6)-linked
glucans were found to be phytoalexin elicitors; they possess antitumor activities as well.
A highly efficient synthesis of tetradecasaccharide 33t was reported again by the Kong
group [225] ( > Scheme 33). The synthesis is based on readily available glucose-derived building blocks 33a, 33b, and 33e and leads via disaccharides 33c and 33d, trisaccharides 33f–33i,
and 33n, hexasaccharides 33j, k, o, p, heptasaccharides 33l, m, q, r to tetradecasaccharide 33s
which was deprotected to furnish target molecule 33t in good overall yield. Such compounds
were also prepared in large scale and with different aglycones [226,227,228].
Mannoglucan from Microellabosperia grisea possesses also high antitumor activity, therefore the repeating unit {[Glcα(1–3)][Glcα(1–6)]Glcβ(1–4)Glcβ(1–4)} n has been synthesized via an efficient route [229]. β(1–6)-Linked galactofuranosyl oligosaccharides are
constituents of the cell wall of bacteria and fungi including some clinically significant
pathogens [230,231,232]. The highly immunogenic arabinogalactans contain arabinofuranosyl and galactofuranosyl residues. β(1–6)-Linked galactofuranose oligomers, also found in
the cell wall of the fungus Fusarium, exhibited in plants elicitor activity. Therefore, a β(1–6)linked O-galactofuranosyl hexasaccharide was prepared based on the trichloroacetimidate
method in high yield [233,234]. The Kong group also synthesized α(1–5)-linked L-arabinofu-
3
Chemical Glycosylation Reactions
5.5 Cell Wall Constituents
Bacterial cell wall peptidoglycan is known as a strong immunopotentiator which induces various mediators such as cytokines, prostaglandins, platelet activation factor, and NO, thus stimulating the immune system [206]. The receptor for peptidoglycans was shown to be TLR2 [207],
the same as for lipoteichoic acids (LTAs) and lipoproteins. Therefore, the synthesis of peptidoglycan fragments is of continuing interest. Recently up to an octasaccharide fragment
was obtained as shown in > Scheme 32 [208,209]. Starting material 32a was transformed
into donor 32b and acceptor 32c based on the temporary protection at O-1 with allyl and at
O-4 with benzylidene. Glycosylation afforded tetrasaccharide 32d which by similar transformation to 32e and 32f led to octasaccharide 32g which could be deprotected to yield target
molecule 32h. This procedure of chain extension could be even extended to the hexadecasaccharide, however the Troc deprotection of this compound failed so far. To the octasaccharide 32h also small peptides were attached via the lactate residue and the biological activity of
the derived compounds was tested.
Many bacterial and fungal cell walls contain homo- and heteroglycans. The synthesis of
fragments of these cell wall constituents has gained increasing interest in the last years. The
Manα(1–3)Manα(1–2)Manα(1–6)Manα(1–2)Man heptasaccharide obtained by mild acetolysis from C. glabrata IFO 0622 has been successfully synthesized by Kong et al. [210]; they
synthesized also a related sulfated pentasaccharide [211]. Also mannan repeating units of
Trichophytan mentagrophytes, T. rubrum [212], Saccharomyces cerevisiae X 2180–1A [213],
and Candida kefyr IFO 0586 [214] have been prepared. Another important class of glycans
are β(1–3)- and β(1–6)-linked glucans which are frequently branched. Glucans consisting
of β(1–3)-linked glucose residues having β(1–6)-linked branches have been found in many
plants and fungi [215,216]. Since these glucans show antitumor activity, the synthesis of at
least minimal structural units for biological activity studies has gained great interest [217].
Recently, several successful syntheses of such molecules have been reported mainly by
Kong et al. [218,219,220,221,222,223]. Also a 2-branched β(1–3)-glucan was found and
dimers of the trisaccharide repeating unit were prepared [224]. 3-Branched β(1–6)-linked
glucans were found to be phytoalexin elicitors; they possess antitumor activities as well.
A highly efficient synthesis of tetradecasaccharide 33t was reported again by the Kong
group [225] ( > Scheme 33). The synthesis is based on readily available glucose-derived building blocks 33a, 33b, and 33e and leads via disaccharides 33c and 33d, trisaccharides 33f–33i,
and 33n, hexasaccharides 33j, k, o, p, heptasaccharides 33l, m, q, r to tetradecasaccharide 33s
which was deprotected to furnish target molecule 33t in good overall yield. Such compounds
were also prepared in large scale and with different aglycones [226,227,228].
Mannoglucan from Microellabosperia grisea possesses also high antitumor activity, therefore the repeating unit {[Glcα(1–3)][Glcα(1–6)]Glcβ(1–4)Glcβ(1–4)} n has been synthesized via an efficient route [229]. β(1–6)-Linked galactofuranosyl oligosaccharides are
constituents of the cell wall of bacteria and fungi including some clinically significant
pathogens [230,231,232]. The highly immunogenic arabinogalactans contain arabinofuranosyl and galactofuranosyl residues. β(1–6)-Linked galactofuranose oligomers, also found in
the cell wall of the fungus Fusarium, exhibited in plants elicitor activity. Therefore, a β(1–6)linked O-galactofuranosyl hexasaccharide was prepared based on the trichloroacetimidate
method in high yield [233,234]. The Kong group also synthesized α(1–5)-linked L-arabinofu-