Acylsulfonamide safety-catch linker: promise and limitations for solid-phase oligosaccharide synthesis.

Jian Yin,Mayeul Collot,Steffen Eller,Peter H Seeberger

doi:10.3762/bjoc.8.232

Abstract

Safety-catch linkers are useful for solid-phase oligosaccharide synthesis as they are orthogonal to many common protective groups. A new acylsulfonamide safety-catch linker was designed, synthesized and employed during glycosylations using an automated carbohydrate synthesizer. The analysis of the cleavage products revealed shortcomings for oligosaccharide synthesis.

Highlights

An acylsulfonamide safety-catch linker 2 (Figure 1), was developed in combination with TentaGel resin to provide orthogonality to temporary ester protecting groups
Safety-catch linkers are useful for solid-phase oligosaccharide synthesis as they are orthogonal to many common protective groups
Key to the success of solid-phase syntheses is the linker that connects the first carbohydrate building block to the solid support [6]. This linker has to remain stable throughout oligosaccharide synthesis but must be cleaved at the end of the reaction sequence to release the oligosaccharide and reveal a functional group for ready conjugation to array surfaces and carrier proteins

Summary

Introduction

Safety-catch linkers are useful for solid-phase oligosaccharide synthesis as they are orthogonal to many common protective groups. An acylsulfonamide safety-catch linker 2 (Figure 1), was developed in combination with TentaGel resin to provide orthogonality to temporary ester protecting groups. In the search for a linker suitable for the solid-phase synthesis of complex glycosaminoglycans (GAGs) [17,18], we designed a new acylsulfonamide safety-catch linker that combined the advantageous features of linker 1, the amino–ester bifunctional linker, and linker 2, the safety-catch linker, to create a connection to the solid support that remains stable under conditions for cleaving temporary ester protective groups.

Results

Conclusion