Anomeric protecting groups

In general, the anomeric centre is the first position to be protected during a series of protecting group manipulations. The anomeric centre can simply be protected as an alkyl, allyl or benzyl glycoside. These glycosides 

The 2-(trimethylsilyl)ethyl group (TMSEt) has found widespread use as anomeric protecting group.49 It can be introduced by a glycosylation (see Chapter 4) and cleaved by treatment with BF3 Et20. The mechanistic considerations of the latter cleavage are as follows a hard base such as a 

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The strong interest in 1-thioaldoses and 1-thioglycosides (66,201) as a consequence of their recent use as anomeric protecting-groups, and concomitantly for glycosyl transfer with the help of thiophilic activators, led to... 

Under harsh acidic conditions the anomeric protecting group is cleaved quantitatively. 

More specific anomeric protecting groups are the 2-trimethylsilylethyl (TMSE) [25] and p-methoxyphenyl glycosides [26], both introduced by glycosylation reactions on protected derivatives (Scheme 3.5). The former is cleaved by treatment with BF3-etherate conditions in which TBDMS ethers survive. p-Methoxyphenyl glycosides are cleaved by CAN-oxidation similarly to p-methoxybenzyl ethers. 

SCHEME 3.22 Examples of regioselective removal of anomeric protecting groups. 

Pleuss, N, Kunz, H, A-Glycosyl amides removal of the anomeric protecting group and conversion into glycosyl donors, Angew. Chem. Int. Ed., 42, 3174-3176, 2003. 

Other uses for glycosylamides have also been described in the literature. Amphiphilic glycosylamides have been demonstrated to be a valuable class of non-ionic biosurfactants (/O). Also, Kunz has used N-glycosylamides as an anomeric protecting group in glycosylation sequences (4). 

These anomeric protecting groups include the allyl, methoxyphenyl (MP), n-pentenyl, 2-trimethylsilylethyl (SE), /-butyldimethylsilyl, and t-butyldiphenylsilyl groups. Removal of this class of protecting groups releases the anomeric hydroxyl function to be converted into leaving groups [8]. 

Figure 2. Two stepwise syntheses (A and C) and block condensation (B). One of the stepwise methods in which synthesis starts from the reducing end (A) has classically been used for oligosaccharide synthesis. The recent development of anomeric protecting groups has enabled alternative synthesis starting from the non-reducing end (C) and a convergent one (B).

A first synthesis of a saccharide-peptide hybrid in a directed synthesis was performed by Yoshimura et al. in 1976 [50], The CAA 51 was activated with cyclo-hexylcarbodiimide and linked to amino sugar 52 to result in dimer 53. This glucuronic acid amide was less soluble in water than the corresponding mannuronic acid derivative. Dimer 53 could be converted, after removal of the anomeric protecting group by hydrogenation, to the amide-linked alditol 54 (Scheme 8) by reduction with sodium borohydride. This publication was not followed up at the time until the interest in carbohydrate mimetics rose [51]. 

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