510
3
Chemical Glycosylation Reactions
eral prominent examples in nature ( > Scheme 37). Therefore, the fully phosphorylated GPI
anchor of Toxoplasma gondii was prepared [271]. Also a new route to rat-brain Thy-1 [272]
was developed which is outlined in > Scheme 38, showing important disconnections and building blocks; it is totally based on trichloroacetimidate donors. Two efficient routes starting
from mannosyl acceptor 39a and glucosamine-derived donor 39e leading to disaccharide 39g
were developed ( > Scheme 39). With variously protected mannosyl donors 39j and 39l, chain
extension to pentasaccharide 39o could be efficiently performed. Transformation into donor
39n and reaction with disaccharide acceptor 39v led to pseudoheptasaccharide 39w. Introduction of two orthogonally protected aminoethyl phosphate residues led to 39aa to which the
phospholipid was attached (→ 39ab). Debenzylation afforded N-Boc-protected 39ac which
permits regioselective attachment of peptide residues to one aminoethylphosphate moiety and
complete deprotection led to target molecule 39ad. This way a highly variable concept for
the synthesis of branched GPI anchors could be established. It is based on versatile building blocks which are readily accessible and provide the desired regio- and stereocontrol. The
concept further allows for the regioselective attachment of peptides or proteins.
The synthesis of a partial structure of a branched pseudohexasaccharide of an inositolphosphoglycan (IPG) has been reported by Martin-Lomas et al. [273]. Linear oligosaccharides of GPIs
were also synthesized based on the trichloroacetimidate method [274,275]. The GPI anchor of
Trypanosoma cruzi containing an unsaturated fatty acid was obtained without any O-benzyl
protection in the decisive intermediate ( > Scheme 40) [276]. Acyl-protected donor 40a and
acyl-protected acceptor 40b gave disaccharide 40c which was transformed into acceptor 40d
which on reaction with donor 40e gave trisaccharide 40f and then acceptor 40g. Glycosylation
with 40h led to tetrasaccharide 40i which was transformed via 40j into donor 40k. From this
compound the desired target molecule was prepared.
5.7 Glycosylation of Various Natural Products and Their Metabolites
Many antibiotics are glycosylated, however the structural complexity of many antibiotics and
their glycosylation is a demanding task. On the basis of the trichloroacetimidate method a successful synthesis of landamycin A hexasaccharide was reported [277]. Novobiocin was glycosylated with three different O-glycosyl trichloroacetimidates as donors at the 7-hydroxy
group [278]. Also the quite sensitive (+)-Neo-carzinostatin aglycone 41a ( > Scheme 41) could
be successfully glycosylated [279]. Reaction of 41a with glycosyl donor 41b furnished the
desired glycoside 41c in good yield which on deprotection afforded target molecule 41d.
Hydroquinone glycosylation leading to α-arbutin was also performed [280]; this compound
is an inhibitor of human tyrosinase and therefore of interest in the cosmetic industry.
Aminoglycoside antibiotics are of special interest as glycosylation targets. Interesting neomycin trisaccharide mimetics have been prepared by Boons et al. [281]. Glycosidase inhibitors
have also been combined with additional carbohydrate residues in order to fine tune their
biological properties. Thus, deoxynojirimycin has been combined with β(1–3)- and β(1–6)linked glucan residues [282].
Many metabolites are glucuronidated, therefore the introduction of the glucuronic acid residue
is a major task because of the low reactivity of the derived donors and their tendency to
4,5-elimination. Therefore, often compounds are first glycosidated and at a later stage of the
3
Chemical Glycosylation Reactions
eral prominent examples in nature ( > Scheme 37). Therefore, the fully phosphorylated GPI
anchor of Toxoplasma gondii was prepared [271]. Also a new route to rat-brain Thy-1 [272]
was developed which is outlined in > Scheme 38, showing important disconnections and building blocks; it is totally based on trichloroacetimidate donors. Two efficient routes starting
from mannosyl acceptor 39a and glucosamine-derived donor 39e leading to disaccharide 39g
were developed ( > Scheme 39). With variously protected mannosyl donors 39j and 39l, chain
extension to pentasaccharide 39o could be efficiently performed. Transformation into donor
39n and reaction with disaccharide acceptor 39v led to pseudoheptasaccharide 39w. Introduction of two orthogonally protected aminoethyl phosphate residues led to 39aa to which the
phospholipid was attached (→ 39ab). Debenzylation afforded N-Boc-protected 39ac which
permits regioselective attachment of peptide residues to one aminoethylphosphate moiety and
complete deprotection led to target molecule 39ad. This way a highly variable concept for
the synthesis of branched GPI anchors could be established. It is based on versatile building blocks which are readily accessible and provide the desired regio- and stereocontrol. The
concept further allows for the regioselective attachment of peptides or proteins.
The synthesis of a partial structure of a branched pseudohexasaccharide of an inositolphosphoglycan (IPG) has been reported by Martin-Lomas et al. [273]. Linear oligosaccharides of GPIs
were also synthesized based on the trichloroacetimidate method [274,275]. The GPI anchor of
Trypanosoma cruzi containing an unsaturated fatty acid was obtained without any O-benzyl
protection in the decisive intermediate ( > Scheme 40) [276]. Acyl-protected donor 40a and
acyl-protected acceptor 40b gave disaccharide 40c which was transformed into acceptor 40d
which on reaction with donor 40e gave trisaccharide 40f and then acceptor 40g. Glycosylation
with 40h led to tetrasaccharide 40i which was transformed via 40j into donor 40k. From this
compound the desired target molecule was prepared.
5.7 Glycosylation of Various Natural Products and Their Metabolites
Many antibiotics are glycosylated, however the structural complexity of many antibiotics and
their glycosylation is a demanding task. On the basis of the trichloroacetimidate method a successful synthesis of landamycin A hexasaccharide was reported [277]. Novobiocin was glycosylated with three different O-glycosyl trichloroacetimidates as donors at the 7-hydroxy
group [278]. Also the quite sensitive (+)-Neo-carzinostatin aglycone 41a ( > Scheme 41) could
be successfully glycosylated [279]. Reaction of 41a with glycosyl donor 41b furnished the
desired glycoside 41c in good yield which on deprotection afforded target molecule 41d.
Hydroquinone glycosylation leading to α-arbutin was also performed [280]; this compound
is an inhibitor of human tyrosinase and therefore of interest in the cosmetic industry.
Aminoglycoside antibiotics are of special interest as glycosylation targets. Interesting neomycin trisaccharide mimetics have been prepared by Boons et al. [281]. Glycosidase inhibitors
have also been combined with additional carbohydrate residues in order to fine tune their
biological properties. Thus, deoxynojirimycin has been combined with β(1–3)- and β(1–6)linked glucan residues [282].
Many metabolites are glucuronidated, therefore the introduction of the glucuronic acid residue
is a major task because of the low reactivity of the derived donors and their tendency to
4,5-elimination. Therefore, often compounds are first glycosidated and at a later stage of the