Sialyl-Le* tetrasaccharide

The UDP-Gal (described in Section 10.4.1) and CMPNeuSAc regeneration systems have been combined in a one-pot reaction. This methodology has been used in the synthesis of the so-called sialyl Le tetrasaccharide 12.24. Four monosaccharides were coupled using j8-l,4-galactosyltransferase, -2,3-sialyl-transferase, and a-l,3-fucosyItransferase in sequence. (Section 10.4.1). It has been reported that kilogram quantities of the sialyl Le tetrasaccharide were prepared in this way (Gijsen et al. 1996). 

Fig. 10) [165], The Cytel corporation in San Diego has been able to scale-up this process for the routine production of kilogram quantities in each run of reactions [144]. The sialyl Le tetrasaccharide and its analogs are of pharmaceutical interest in the context of new treatments for chronic inflammatory diseases (psoriasis, rheumatoid arthritis), tumors, and tissue injuries following a heart attack, stroke, or organ transplant. Sialyl Lex and its analogs are therefore enthusiastically pursued by several pharmaceutical companies. Strategies for the solid-phase chemoenzymatic synthesis of glycopeptides (and glycolipids) containing sialyl Lex have also been designed and reported [144,156, and references therein].

Glycosylamines produced by reaction of unprotected sugars (e.g. LacNAc, Le trisaccharide and sialyl-Le tetrasaccharide) with the photoreactive, carbene-... 

Multistep enzymatic transformations can be done with combinations of compatible aldolases, glycosyltransferases and recycling systems. A practical and successful example for this concept is the multienzymatic synthesis of the sialyl Lewisx tetrasaccharide (sialyl Le ... 

In the second approach, treatment of lactoside derivatives 19 and 63 with benzaldehyde dimethylacetal in dry acetonitrile using p-toluenesulfonic acid as catalyst gave the 4, 6 -0-benzylidene derivatives 66 and 67 in 93% and 89% yield, respectively. Further derivatization of 23 (Scheme 4) was also considered in order to prepare sialyl Le as shown in Scheme 15. The disarmed-latent trisaccharide acceptor 23 was first coupled with ethylthio fucopyranosyl donor 57 in the presence of NIS/TfOH in dichloromethane at —70°C to give sialylated tetrasaccharide 70 in 63% yield together with recovered trisaccharide acceptor 23 (17%) and a minor unidentified regioisomer (less than 10%) (Scheme 15). 

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