Silylated glycosylation

O-glycosidation between O-silylated glycosyl acceptors and several 1-substituted sugars, glycopyranosyl or furanosyl silyl ethers [79a], fluorides [80], phosphates [81], and trichloroacetimidates [82a] has been examined to develop other efficient and stereoselective procedures catalyzed by silicon Lewis acids. The trichloroacetimidate glycosyl donors are fairly reliable and were used for the synthesis of eanelioside GD by Ogawa (Fig. l)[82b]. 

Insoluble chitin 2211 is readily silylated by HMDS 2 and Me3SiCl 14 to form the soluble, much more lipophilic 2212, whose 6-silyloxy groups can either be tri-tylated with PhsCCl or glycosylated with the peracetylated oxazolidine 2213, derived from D-glucosamine, in C1(CH2)2C1 in the presence of camphorsulfonic acid (CSA) to give, on work-up with methanol, the branched chitin 2214 in high yields [22] (Scheme 14.8). 

Reumycin 311 was silylated with F3CC( = A-SiMe3)-OSiMe3 to give 411, which was glycosylated with tetra-0-acetyl-/3-D-ribofuranose 412 to... 

Figure 2.6 Clycosyltion of silylated acceptor by glycosyl fluoride.

Silicon presents an attractive option among eledrophilic activating and dehydrating agents of hemiacetals because of the wide commercial availability of eledrophilic silicon sources. The two main classes of silicon electrophiles used, namely silyl halides and silyl sulfonates, have been demonstrated to promote a variety of glycosylations including some examples of oligosaccharide synthesis. 

One of the earliest reports of silicon-based eledrophilic adivation comes from the Koto laboratory on the use of silyl halide eledrophiles to promote the dehydrative glycosylation with hemiacetal donors [40,41]. In the readion (Scheme 3.5),... 

In fact, other studies have shown that TMSOTf catalyzes the glycosylation of a silylated acceptor with a silylated hemiacetal donor [49]. Nudel man s procedure was applied to the synthesis [1-glucuronide 30, isolated in 57% yield. Kiyoi and Kondo have applied the TMSOTf activation protocol to protected L-fucose hemiacetal donors for glycopeptide synthesis and obtained glycopeptide fragment 31 in 74% yield (a p, 20 1) [50], Posner and Bull have developed a procedure that uses excess TMSOTf in the presence of molecular sieves (SYLOSIV A4) to synthesize various l.l -linked disaccharides such as the galactopyranose dimer 32 [51,52]. 

Takahashi and coworkers described the one-pot synthesis of core 2 branched oligosaccharides [236], It was found that boron trifluoride complexed with a tri-methylsilyl ether would enhance the nucleophilidty of the silyl ether. As a result, glycosylations of the 6-O-TMS modified acceptor with a glycosyl fluoride provided... 

The problem of the nucleophilicity of amides in glycosylation reactions is not limited to the sulfoxide method and has been shown to result in the formation of glycosyl imidates from intermolecular reaction with activated donors. It appears that this problem may be suppressed by the prior silylation of the amide [348,349]. Accordingly, it may be sufficient to operate the sulfoxide method with an excess of triflic anhydride when amides are present so as to convert all amides into O-triflyl imidates, which are then hydrolyzed on work-up. Despite these problems, several examples have been published of successful sulfoxide glycosylation reactions with acceptors carrying remote peptide bonds [344,345] and with donors coupled to resins via amide-based linkages [346,347], with no apparent problems reported. Sulfonamides and tertiary amides appear to be well tolerated by the sulfoxide method [340,350],... 

Lactone derivatives derived from glucuronic add were used as glycosyl donors by Murphy and coworkers [250], These glycosyl donors were found to react with silyl... 

---