Sialyl acceptor

Another effective a-selective sialylation involves the use of a 5-N,4-0-carbonyl-protected sialyl donor, which could efficiently be used for the preparation of an a(2,8)-tetrasialoside. It was found that the 5-N,4-0-carbonyl protecting group improves the reactivity of the C-8 hydroxyl group of the sialyl acceptor [168]. 

Similar to the reactivity tuning of sialyl donors mentioned above, it was found that the modification of the C5 acetamido group or its substitution by other functionalities also raises the reactivity of the C8 hydroxyl of sialic acid. Boons and co-workers originally synthesized iV,iV-diacetyl sialyl acceptor 144, which was applied to the sialylation with lV,lV-diacetyl sialyl donor 93 in MeCN at —40 °C. In comparison to iV-acetyl sialyl acceptor 145, the sialylation produced Q -(2-8)-disialic acid 146 in raised yield (50%, aip = 2/1) (O Scheme 40) [94,95]. 

Similarly, the coupling reaction between the A-Troc sialyl donor and acceptor proved effective. 2-Trifluoroacetimidate-5-A-Troc donor 152 was reacted with A-Troc sialyl acceptor 153 in the presence of a catalytic amount of TMSOTf at —78 °C in MeCN-CH2Cl2 to afford the dimer 154 in 71% yield as a stereo mixture (a/ = 67/33) (O Scheme 42) [114]. 

Several 3D protein structures of bacterial SiaTs have been determined in the presence of GMP-Neu5Ac as a ligand [60]. Based on these crystal structures, from which the active site organization and the catalytic mechanism have been elucidated, SiaT enzymes can be predicted to tolerate rather flexibly structural variations in the sialic acid part. This can be rationalized because only the nucleotide portion and the sialic acid substructure around the anomeric center become buried into the active site upon substrate binding and orientation toward the sialyl acceptor substrate, whereas much of the remainder of the siahc acid portion remains oriented toward the protein surface or even in contact with bulk solvent. This hypothesis has been verified by a number of preparative studies [33,47, 61). 

Scheme 17.13 Chemoenzymatic one-pot synthesis of sialyl acceptor substrates N-acetyl-o-lactosamine glycoside (R=NHAc) and the corresponding lactoside (R = OH).

The E. coli K1 polyST complex catalyzes the transfer of Sia from CMP-Sia to both endogenous and exogenous sialyl acceptors which contain preexisting... 

BF3-OEt2 Unnatural P-sialoside derivatives are produced preferentially by using O-acetylated glycosyl fluoride donor and BF3-OEt2 as the promoter. When P-sialyl fluoride derivative 28 was reacted with acceptor 22 in the presence of BF3-OEt2 in dichloromethane, the P-sialoside 28 was obtained in a mixture of anomers (a/p 17/83) (Scheme 2.11) [44],... 

Substrate-specificity studies on microsomal, frog-liver sialyltrans-ferase revealed the presence of (2—>3) and (2—>6) activities.277 This enzyme system readily sialylates oligosaccharides, but is almost inactive with asialofetuin, which is in contrast to the sialylation of oligosaccharides, as well as asialofetuin, by rat-liver sialyltransferase.278 The conclusion from this observation is that acceptor specificity of sialyl-transferases isolated from liver of evolutionary distant animals is similar for substrates of low molecular weight, but differs for compounds of high molecular weight.279... 

In the initial studies, as briefly described earlier, the methyl a-2-thioglycoside of Neu5Ac 5 [22,24], or the -1 1 anomeric mixture 11 [26,27], which can be almost quantitatively prepared from 9 in one step, was coupled with lightly protected sugar acceptors such as 14,16, and 18 in the presence of DMTST in acetonitrile to give exclusively the sialyl a(2—>3)- or sialyl ot(2—>6)-D-galactose or lactose derivatives (20, 22, and 24) in 50-70% yields even in large-scale reactions [26],... 

Table 2 NIS-TfOH-Promoted Oligo-sialylation of Sugar Acceptors by Phenyl 2-thioglycosides of Dimeric and Trimeric NeuSAc in Acetonitrile...

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