2-Thioglycoside sialyl donors

Wong and coworkers showed that 5-azido sialyl donors protected with O-acetyl ester are useful for a-selective glycosylations of primary hydroxyls (Scheme 4.6e) [169]. It was proposed that the linear and electron-withdrawing nature of the C-5 azido moiety stabilizes the reactive axial acetonitrile adduct to allow the incoming nucleophile to approach the a-face in an SN2-like fashion. In addition, a chemose-lective glycosylation method has been developed for the synthesis of NeuAca-(2 —> 9) NeuAc as thioglycoside donor for use in the subsequent glycosylations [169]. 

Almost all types of leaving groups have been explored in sialyl donors with, until recently, two notable exceptions the venerable imidates and the sulfoxides. While the preparation of stable, isolable sialyl trichloroacetimidates has still to be demonstrated, the recent innovation of the Biao Yu group—the (V-phenyltrifluoroacctimidatcs—has proven equal to the task and has provided access to new potent class of sialyl donors [27], Stable sulfoxides of sialyl thioglycosides have also been described recently and employed as glycosyl donors on activation with triflic anhydride (Tf20) [28], The S-benzoxazolyl (.S -Box) thiosialosides constitute another recent addition to the armory of sialyl donors [29, 30],... 

In 1996, a new type of thioglycoside donor, the A, lV-diacetyl sialyl donor, was devised by Boons and co-workers. This is the beginning of the third period. The iV,iV-diacetyl sialyl donor was followed by other analogous C5-modified sialyl donors. Very recently, Tanaka and his coworkers have developed the 5-iV-4-0-oxazolidinone sialyl donor, which can provide a-sialo-side without assistance of the nitrile solvent effect despite the absence of an auxiliary at the C3 or Cl positions. 

SCHEME 5.3 Effect of (V,(V-diacetylation of a thioglycoside donor on sialylation. Bz, benzoyl TMS, trimethylsilyl Ts, toluenesulfonyl. 

Another example came from the Wong group [24], To synthesize the S SEA-4 hexasaccharide 94, they started from the dibutyl sialyl phosphate 91, which was coupled to thioglycoside 92 with TMSOTf as the activator (Scheme 6.18). The N-acety-lated oxazolidinone moiety in donor 91 was crucial for the high a selectivity in the sialylation reaction. Subsequent coupling to acceptor 93 in the presence of NIS afforded 94 in 78% yield for the two steps. 

Facile and highly regio- and a-stereoselective sialyl glycoside syntheses have been achieved by using, as glycerol donors, the 2-thioglycosides (11-13) of NeuSAc or... 

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