Sialyl xanthate

Scheme 4.74 Sialyl xanthate in regioselective and stereoselective glycosylations [398].

Several other examples of successful application of sialyl xanthates for oligosaccharide synthesis have been reported [411,413-427]. 

Martichonok, V, Whitesides, G M, Stereoselective a-sialylation with sialyl xanthate and phenylsulfenyl triflate as a promotor, J. Org. Chem., 61, 1702-1706, 1996. 

The Whitesides group achieved a more efficient synthesis of a-sialosides from sialyl xanthates by modifying the reaction conditions of Sinay s system [11]. Previously, Lonn and coworkers had demonstrated that lower temperatures and the use of milder promoter, methylsulfenyl trifiate, increased the product yield and reaction stereoselectivity [12]. Whitesides and coworkers introduced an even milder promoter, phenylsulfenyl trifiate (PST), which itself was prepared in situ from silver trifiate and phenylsulfenyl chloride [11]. When sialylations of xanthate donor 27 were pro-... 

O Scheme 21) [80,81,82]. Bilberg and Lonn also found the significance of solvent for glycoside formation the use of a mixture of MeCN-CH2Cl2 (3/2) afforded the best result. The optimized activation system extended the usage of 2-xanthate derivative 63 to the assembly of a variety of sialyl oligosaccharides as shown in Fig. 8 [83,84]. 

Figure 9.3 Proposed mechanism of nitrihum solvent assisted a-sialylation. 2-Phosphites and xanthates...

A-Acetylneuraminic acid contains no C-3 substituent but carries a carboxy group at position 2. Both factors complicate the stereoselective and efficient formation of the desired a-2,3-sialoside in example 2 [31], A neighboring group at C-3, required for stereoselective synthesis, can be introduced temporarily (SPh, SePh) and removed after completion of the sialylation [32]. This strategy, however, requires additional steps and results in reduced overall yield. Recently, thioalkyl/aryl sialosides and 5-sialosyl xanthates have been used to achieve regio- and stereoselective formation of a-glycosides of iV-acetyl neuraminic acid derivatives (Scheme 6) [33-35]. 

Early work employing DMTST as the glycosyl promoter showed [27] that sialyl 2-xanthate 60 reacts with Gal acceptor 61 or 6 in acetonitrile to give predominantly... 

To solve the problem in sialidation (1) introduction of an auxiliary group at C-3 in sialyl donors, (2) specific activation of the anomeric carbon C-2 by use of thioglyco-sides, xanthates or phosphites in acetonitrile medium, and (3) the use of sterically less hindered sugar acceptors have been attempted and found to be highly effective for obtaining a-sialosides in a regio- and stereospecific manner. Combinations of these procedures have resulted in further improvements. 

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