A Second‐Generation Tandem Ring‐Closing Metathesis Cleavable Linker for Solid‐Phase Oligosaccharide Synthesis

Abstract

A tandem ring‐closing metathesis cleavable linker system for solid‐phase oligosaccharide synthesis has been developed. The acid‐ and base‐stable linker can be readily cleaved with Grubbs second‐generation catalyst without the use of alkene additives to liberate the assembled oligosaccharides from the solid support. Application of the linker was shown in three solid‐phase oligosaccharide synthesis campaigns. Two frame‐shifted hyaluronic acid fragments were prepared, and we also report the synthesis of a trimeric β‐1,3‐glucan fragment, in which, next to the linker, our recently reported 4‐azido‐2,2‐dimethylbutanoyl (AzDMB) protective group was applied.

Profluorescent substrates for the screening of olefin metathesis catalysts

“…Upon relay ring-closing metathesis, the fluorophore and quencher are disconnected resulting in the fluorescent product 7 . A similar linker concept has previously been implemented for a solid-phase linker in the synthesis of oligosaccharides [ 18 – 19 ]. The second profluorescent molecule selected was diolefin 8 , which yields fluorescent 7-hydroxycoumarin (umbelliferone) ( 9 ) upon ring-closing metathesis.…”

Traceless Photolabile Linker Expedites the Chemical Synthesis of Complex Oligosaccharides by Automated Glycan Assembly

“…Repetitive cycles consisting of glycosylation, capping, and selective deprotection steps extend the glycan chain to the desired structure. Different linkers for AGA were explored (Figure 1), including metathesis-labile linker 1 , 6 base-labile linker 2 , 7 and photocleavable linkers 3 and 4 . 8 Photocleavable linkers such as 3 and 4 are often referred to as “traceless” because the on-resin removal of photosensitive groups requires exposure only to light to release the product into the solution.…”

Chemical Synthesis of Oligosaccharides Related to the Cell Walls of Plants and Algae

“…For oligosaccharides up to the pentasaccharide level, an iterative approach has been used, which has enabled the synthesis of tri-, tetra-and pentasaccharides in the same sequence, as exemplified by the preparation of β-(1→3)-D-glucan oligosaccharides reported by Vetvicka and co-workers (Scheme 6). 55,56 For the synthesis of longer β-D-glucan oligosaccharides in solution, the use of convergent strategies employing di- 53,[59][60][61][62]64 , tri- 54,[57][58][59]64 , tetra- 52,64 and pentasaccharide 52,59 building blocks has been demonstrated to be advantageous, as it reduces the number of steps. This type of approach has been used to synthesize long linear 52,62 and branched 52,59,64 oligosaccharides.…”