Linker Octenediol

Scheme 5.13 Cleavage of an octenediol linker by olefin cross-metathesis to yield NPG63.69...

Scheme 6.10 Solid-phase synthesis of oligosacchraides using an octenediol linker.

An exception to this was a report in 2003 by Seeberger and co-workers, where catalyst 6 was found to cleave the octenediol linker of an azide-containing sugar in high yield (Scheme 16). Use of 1-pentene as a cross-partner in place of ethylene proved crucial to attaining high reaction yields. This methodology was later successfully adapted to solid-phase synthesis. 

FIGURE 7.3 Oligosaccharides synthesized by automation using octenediol or butenediol linkers and the major milestones achieved. Piv, pivaloyl TCA, trichloroacetyl. 

In a similar fashion, Seeberger s group has developed an octenediol-derived linker for polysaccharide synthesis which is cleavable by CM with ethylene gas [148,149],... 

Fraser-Reid et al. [21,22] reported the synthesis of polymer supported oligosaccharides using n-pentenyl glycosides, while Seeberger et al. [23] accomplished the synAesis of p-(l- 4)- and p.(2 6)-linked ohgosaccharides using glycosyl phosphates combined with an octenediol linker. 

Fully protected tumor-associated carbohydrate antigen Globo-H (50), a potential breast and prostate cancer vaccine [54, 55], was assembled by automated solid support synthesis using oct-4-ene-l,8-diol linker 49 and building blocks 51-56 (Scheme 20.15). The linker is stable to acid and base but is cleaved cleanly by olefin metathesis [56]. The octenediol linker performs best on Merrifield s PS resin, affording routinely loadings in a range of 0.1-0.3 mmol g 1. 

The solid phase polysaccharide synthesis is performed on Metrifield s polystyrene resin functionalized with 4-octenediol linker. This linker is stable during the synthesis cycles but can be cleaved by Gmbbs catalyst (cross-metathesis reaction) resulting in fuUy protected polysaccharide, which can be used for further functionalization or deprotected in its native state. The final purification is achieved by high-performance hquid chromatography, which in some cases also can be used to separate the different stereoisomers of the final products [58]. 

Others have also employed this metathetical cleavage approach toward the chemoselective cleavage of oleflnic substrates. For example, a similar approach was taken using an octenediol-based linker system 26 toward the cleavage of saccharides 27 (Scheme 6.6). ... 

A similar method has been developed by Seeberger et al. for metathesis reaction with pentene to give octene-substituted monosaccharide derivatives [373]. In previous solution phase experiments three catalysts were screened at different temperatures and in different solvents which suggest that metathesis proceeds best in dichloromethane at 0°C and with (H2lmes)(3-Br-py)2-(Cl)2Ru = CHPh] as the catalyst. AU soUd phase experiments have been performed on Merrifield octenediol linker 731 and have been checked for the cleavage reaction with ethylene as described in Scheme 109 for the synthesis of terminal olefins. 

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