Glycosylation using Glycosyl Phosphites

Watanabe, Y, Nakamoto, C, Yamamoto, T, Ozaki, S, Glycosylation using glycosyl phosphite as a glycosyl donor. Tetrahedron, 50, 6523-6536, 1994. 

Salicylic acid was used for phosphite protection in the synthesis of glycosyl phosphites and phosphates. This derivative is very reactive and readily forms a phosphite upon treatment with an alcohol or a phosphonic acid upon aqueous hydrolysis. ... 

A phosphite forms the phosphonium salt by interaction with a Lewis acid owing to their basic character. When a glycosyl phosphite is transformed to the phosphonium salt, the resulting phosphonooxy group acts as a strong leaving group in a nucleophilic substitution at the anomeric carbon. Since the early reports on their use... 

Glycosyl phosphites were introduced by Schmidt [451-453], Wong [454-457] and Watanabe [458,459], A variety of dialkyl and cyclic phosphites has proved suitable for the reaction [459,460], In fact, diethyl and dibenzyl phosphites are the most frequently used. Glycosyl phosphites react with alcohols at low temperamres in the presence of catalytic amounts of Lewis acid promoters such as TMSOTf, BF3-Et20 and Sn(OTf)2, thus creating glycosides. Phosphites are also activated by other promoters, which are summarized in Table 4.9. 

SCHEME 4.44 S3fnthesis of 3-O-neuraminyllactose using glycosyl phosphite. 

Besides the common organic solvents used for glycosylations, syntheses of glycosides from glycosyl phosphites in ionic liquids were recently reported [463]. Glycosyl phosphites are frequently used for sialylations [451,454] and a typical example is shown in Scheme 4.44. As illustrated, reaction of the (3-neuraminyl phosphite 205 with the lactose diol 206 afforded the 3-(9-neuraminyllactose derivative 207 in a 55% yield [460]. 

P,P-Diphenyl-A-tosyl-phosphinimidates 218 were used with Bp3-Et20 and TMSOTf promoters [491-493], and A,A,A A -tetramethylphosphorodiamidates 219 were also activated by the same catalysts [279,493,494]. These latter compounds are more stable than the previous types, and can also serve as glycosyl acceptors under certain conditions. For example, they could be glycosylated with glycosyl phosphites, diphenylphosphinimidates and phosphoro-diamidimidothioates [279]. Moreover, they could also be used in armed-disarmed type glycosylations [279,495]. 

Lin, C-C, ShimazaM, M, Heck, M-P, Aoki, S, Wang, R, Kimura, T, Ritzen, H, Takayama, S, Wu, S-H, Weitz-Schmidt, G, Wong, C-H, Synthesis of sialyl Lewis X mimetics and related structures using the glycosyl phosphite methodology and evaluation of E-selectin inhibition, J. Am. Chem. Soc., 118, 6826-6840, 1996. 

Hashimoto and coworkers successfully applied their phosphite method to selective -manno-sylation [63,64,65] (O Scheme 21), Similar to the case of Crich s mannosylation, cyclic protection at the 4- and 6-positions is essential. Mannosyl phosphate and phosphoramidate were also investigated [65,66]. Toshima et al. used the glycosyl phosphites activated with a solid acid catalyst to give -mannoside predominantly [67,68]. 

Glycosyl phosphites. The diethylamino thus on reaction with sugars in the presence of formed. These products are not only useful as dized to the phosphates, which are precursors... 

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