Solid-phase oligosaccharide synthesis linker

L. G. Melean, W. C. Haase and P. H. Seeberger, A novel 4,5-dibromooctane-l,8-diol linker for solid-phase oligosaccharide synthesis, Tet. Lett., 2000, 41, 4329 1333. 

Andrade RB, Plante OJ, Melean LG, Seeberger PH. Solid-phase oligosaccharide synthesis Preparation of complex structures using a novel linker and different glycosylating agents. Org. Lett. 1999 1 1811-1814. 

Fukase, K, Nakai, Y, Egusa, K, Porco, J A, Kusumoto, S, A novel oxidatively removable linker and its application to a-selective solid-phase oligosaccharide synthesis on a macroporous polystyrene support, Synlett, 1074-1078, 1999. 

Scheme 6.192 shows the o-nitrobenzyl moiety used as a photolabile linker in the solid-phase oligosaccharide synthesis on a polystyrene (PS) support.1208 After the synthesis of the protected oligosaccharide 404, PS attached to the photoremovable group is removed by photolysis and the final product is obtained by hydrogenolysis. Such a strategy could be promising for combinatorial synthesis of oligosaccharide libraries. 

Scheme 20.19 An alkylthiol linker for solid phase oligosaccharide synthesis.

Solid-phase Oligosaccharide Synthesis. Methanesulfonyl chloride resin 1 was used as an activating linker in the synthesis of various polymer-bound di and trisaccharides 2 (eq 1). The sulfonate linker proved stable to glycosidation and alcohol deprotection conditions, and nucleophilic displacement of 2 by Nal provided 6-iodosaccharides (eq 1). NaOAc and NaNs were also suitable nucleophiles for cleavage of the sulfonate linker. ... 

Support-bound triacylmethanes (e.g. 2-acetyldimedone) readily react with primary aliphatic amines to yield enamines. These are stable towards weak acids and bases, and can be used as linkers for solid-phase peptide synthesis using either the Boc or Fmoc methodologies, as well as for the solid-phase synthesis of oligosaccharides [456]. Cleavage of these enamines can be achieved by treatment with primary amines or hydrazine (Entries 2 and 3, Table 3.23 see also Section 10.1.10.4). 

Although solid-phase chemistry is well developed, progress has not yet been fully extended to oligosaccharide chemistry, because of the high demands on the polymer support and the lack of powerful analytical tools for monitoring reactions on solid phases. The synthesis of an a(l-2)-linked pentamannose moiety has recently been reported (Scheme 45) [193] a Merrifield resin, a thio-linker, and a 2-0-acetyl protected mannosyl trichloroacetimidate were used. The glycosylation reaction was... 

Table 3. Major linkers used in two-phase (solid state) oligosaccharide synthesis showing chemical structure of the linker, glycosylating agent, and removal methods used. 

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