488
3
Chemical Glycosylation Reactions
studies [137]. Sulfated sialyl Lewis X variants, containing a lactamized sialyl residue, were
obtained by the Kiso-Ishida group ( > Scheme 21) [138]; these compounds were found to be
potent antigenic determinants. Following the standard procedure 21a and 21b gave 21c, which
was transformed via 21d–h into lactamized target molecules 21i and 21j. Also chemoenzymatic synthesis was successfully engaged in the synthesis of sulfated sialyl Lewis X connected to
a core 1 mucin (T antigen) structure ( > Scheme 22) [139]. From 22a, b disaccharide 22c was
obtained, which was transformed into donor 22d giving with acceptor 22e tetrasaccharide 22f.
Partial deprotection (→ 22g, h), regioselective sulfation and final deprotection gave 22i; enzymatic sialylation and fucosylation led to target molecules 22j and 22k.
Some α-galactosyl ceramides with a phytosphingosine residue, isolated from the marine
sponge Agelas mauritianus, were found to possess strong in vivo activities against several murine tumor cells [140,141]. The synthesis of analogs exhibited that compound 23e
( > Scheme 23) is a potent candidate for clinical trials [142]; 23e was also found to have
immunostimulatory activity [143]. These findings promoted a great demand for this compound, therefore, several syntheses of 23e and analogs have been reported [144]. The Schmidt
group reported an efficient synthesis which is based on galactosyl trichloroacetimidate 23a as
donor and phytosphingosine derivative 23b as acceptor which led to the α-linked intermediate 23c. Azide introduction (→ 23d), hydrogenolysis of protecting groups and N-acylation
furnished target molecule 23e very efficiently.
Lipid-linked T and T n antigens [145] and glycosidated phosphoglycerolipids [146] were also
synthesized based on O-glycosyl trichloroacetimidates donors. In a comparative study glucopyranosylation of methyl ω-hydroxy-hexadecanoate with different glucosyl donors was carried out which demonstrated the advantageous properties of the trichloroacetimidate donor;
this way the desired β-linked target molecule for biological studies was readily obtained [147].
3,4,5-Tris(alkyloxy)benzyl glycosides were prepared with standard O-glycosyl trichloroacetimidates as donors [148]. The three lipid chains permitted the immobilization of these compounds on a hydrophobic surface and lectin affinity studies by surface plasmon resonance.
5.2 Glycosyl Amino Acids and Glycopeptides
The availability of O- or N-glycosyl amino acids as building blocks for glycopeptide or eventually glycoprotein synthesis is of great importance. Therefore, various synthetic methods
have been reported [149,150]. Direct O-glycosylations of serine and threonine derivatives with
O-glycosyl trichloroacetimidates as donors have been reported [151,152]. The straightforward
hexafluoroacetone O,N-protection of Ser, Thr, Pyp, and Tyr gave generally the best results
with trichloroacetimidate donors as shown in > Scheme 24 [153] on glucosylation of 24a, d, g
with per-O-acetylated glucopyranosyl donors affording 24b, e, h. As this protection also leads
to an activated carboxylate group, protecting group cleavage and peptide chain extension can
be combined furnishing dipeptides 24c, f, i.
The presence of the Glcα(1–2)Galβ(1-O)Hyl moiety in collagen was reason to synthesize this
building block [154]. Replacement of the ω-amino group of Hyl by an azido group and protection of the α-amino group by the Z group and the carboxylate group by a t-butyl group
led cleanly to the target molecule after two glycosylation steps. Glycosylation of Fmoc-protected Ser, Hse, and Thr with T N , T, and ST-derived glycosyl donors were also success-
3
Chemical Glycosylation Reactions
studies [137]. Sulfated sialyl Lewis X variants, containing a lactamized sialyl residue, were
obtained by the Kiso-Ishida group ( > Scheme 21) [138]; these compounds were found to be
potent antigenic determinants. Following the standard procedure 21a and 21b gave 21c, which
was transformed via 21d–h into lactamized target molecules 21i and 21j. Also chemoenzymatic synthesis was successfully engaged in the synthesis of sulfated sialyl Lewis X connected to
a core 1 mucin (T antigen) structure ( > Scheme 22) [139]. From 22a, b disaccharide 22c was
obtained, which was transformed into donor 22d giving with acceptor 22e tetrasaccharide 22f.
Partial deprotection (→ 22g, h), regioselective sulfation and final deprotection gave 22i; enzymatic sialylation and fucosylation led to target molecules 22j and 22k.
Some α-galactosyl ceramides with a phytosphingosine residue, isolated from the marine
sponge Agelas mauritianus, were found to possess strong in vivo activities against several murine tumor cells [140,141]. The synthesis of analogs exhibited that compound 23e
( > Scheme 23) is a potent candidate for clinical trials [142]; 23e was also found to have
immunostimulatory activity [143]. These findings promoted a great demand for this compound, therefore, several syntheses of 23e and analogs have been reported [144]. The Schmidt
group reported an efficient synthesis which is based on galactosyl trichloroacetimidate 23a as
donor and phytosphingosine derivative 23b as acceptor which led to the α-linked intermediate 23c. Azide introduction (→ 23d), hydrogenolysis of protecting groups and N-acylation
furnished target molecule 23e very efficiently.
Lipid-linked T and T n antigens [145] and glycosidated phosphoglycerolipids [146] were also
synthesized based on O-glycosyl trichloroacetimidates donors. In a comparative study glucopyranosylation of methyl ω-hydroxy-hexadecanoate with different glucosyl donors was carried out which demonstrated the advantageous properties of the trichloroacetimidate donor;
this way the desired β-linked target molecule for biological studies was readily obtained [147].
3,4,5-Tris(alkyloxy)benzyl glycosides were prepared with standard O-glycosyl trichloroacetimidates as donors [148]. The three lipid chains permitted the immobilization of these compounds on a hydrophobic surface and lectin affinity studies by surface plasmon resonance.
5.2 Glycosyl Amino Acids and Glycopeptides
The availability of O- or N-glycosyl amino acids as building blocks for glycopeptide or eventually glycoprotein synthesis is of great importance. Therefore, various synthetic methods
have been reported [149,150]. Direct O-glycosylations of serine and threonine derivatives with
O-glycosyl trichloroacetimidates as donors have been reported [151,152]. The straightforward
hexafluoroacetone O,N-protection of Ser, Thr, Pyp, and Tyr gave generally the best results
with trichloroacetimidate donors as shown in > Scheme 24 [153] on glucosylation of 24a, d, g
with per-O-acetylated glucopyranosyl donors affording 24b, e, h. As this protection also leads
to an activated carboxylate group, protecting group cleavage and peptide chain extension can
be combined furnishing dipeptides 24c, f, i.
The presence of the Glcα(1–2)Galβ(1-O)Hyl moiety in collagen was reason to synthesize this
building block [154]. Replacement of the ω-amino group of Hyl by an azido group and protection of the α-amino group by the Z group and the carboxylate group by a t-butyl group
led cleanly to the target molecule after two glycosylation steps. Glycosylation of Fmoc-protected Ser, Hse, and Thr with T N , T, and ST-derived glycosyl donors were also success-