The Remote Activation Concept

The well-known effect of C-2 participating (e.g., ester) and nonparticipating (e.g., O-benzyl) groups [1] can be used in predicting the sterochemical outcome of the new glycosidic linkage (e.g., 1,2-trans or 1,2-cis as major or exclusive products). 

Glycosidation of simple and complex aglycones without the need for protection of the hydroxy groups in the donor (e.g., macrolide antibiotics) 

Possible extension to solid-phase synthesis of glycosides, avoiding protection-deprotection steps 

Consideration of newer generations of leaving groups from lessons learned 

The design of a prototypical leaving group that would activate the anomeric carbon atom in an unprotected glycosyl donor presents major challenges and problems, namely  

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Glycoside Synthesis Based on the Remote Activation Concept An Overview... 

The first generation of an O-unprotected glycosyl donor that could be activated based on the remote activation concept was exemplified by 2-pyridylthio p-D-glucopyranoside 1 [10], which could be easily prepared from acetobromoglucose [11]. Treatment of 1 with a variety of alcohols in the presence of mercuric nitrate in acetonitrile solution led, within a few minutes, to the corresponding O-glycosides, with isolated yields and a/p ratios varying from methanol (70 30, 95%), to 2-propanol (62 38 77%), and cyclohexanol (51 49, 75%) Scheme 2. Identical results were obtained when 2-pyrimidinylthio p-D-... 

Scheme 1 The design of glycosyl 2-pyridylcarbonate or glycosyl 2-thiopyridylcarbonate (TOP-CAT) donors based on the remote activation concept.

B. Lou, G. V. Reddy, H. Wang, and S. Hanessian, Glycoside and oligosaccharide synthesis with unprotected glycosyl donors based on the remote activation concept, in S. Hanessian, (Ed.), Preparative Carbohydrate Chemistry, Marcel Dekker, Inc., New York, 1997, p. 389. 

Hanessian, S. Glycoside synthesis based on the remote activation concept an overview. In Preparative Carbohydrate Chemistry. Hanessian, S. (ed.) Marcel Dekker New York, 1997, pp. 381-388. 

Such benzyl-protected pyranoses as l-0-acetyl-2,3,5-tri-0-benzyl-p-D-ribo-furanose or l-(9-acetyl-2,3,4,6-tetra-0-benzyl-a-D-mannopyranose do not give single glycosyl azides but lead to anomeric mixtures. Thus 2,3,4,6-tetra-O-benzyl-ot- (97) and -p-o-mannopyranosyl azide (98) were obtained in the ratio 1 1.2. In his book Hanessian reports on a process based on the remote activation concept . For example, 3-methoxy-2-pyridyl p-o-glucopyranoside... 

Hanessian and Lou have reviewed the remote activation concept applied with 0-unprotected glycosyl donors e.g. 1 which, with methyl triflate, give access to a-glucosides. This approach can also be used to make glycosyl carboxylates. 

The authors suggest that the displacement is facilitated by chelation of the metal atom to the carbonyl oxygen (or thiocarbonyl sulfur) and the N-3 of the imidazolyl group. This can be related to the remote activation concept originally introduced by Hanessian [112]. 

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