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

Kim Le Mai Hoang,Peter H Seeberger,Mirco Loria,Yang Yu,Yuntao Zhu,Martina Delbianco,Alonso Pardo-Vargas

doi:10.1021/jacs.9b03769

Abstract

Automated glycan assembly (AGA) aims at accelerating access to synthetic oligosaccharides to meet the demand for defined glycans as tools for molecular glycobiology. The linkers used to connect the growing glycan chain to the solid support play a pivotal role in the synthesis strategy as they determine all chemical conditions used during the synthesis and the form of the glycan obtained at the end of it. Here, we describe a traceless photolabile linker used to prepare carbohydrates with a free reducing end. Modification of the o-nitrobenzyl scaffold of the linker is key to high yields and compatibility with the AGA workflow. The assembly of an asymmetrical biantennary N-glycan from oligosaccharide fragments prepared by AGA and linear as well as branched β-oligoglucans is described to illustrate the power of the method. These substrates will serve as standards and biomarkers to examine the unique specificity of glycosyl hydrolases.

Highlights

The procurement of complex oligosaccharides in satisfactory quantities and quality as tools for glycobiology remains challenging
Automated glycan assembly (AGA) relies on the delivery of building blocks to a suspension of a solid support that is equipped with a linker, followed by the addition of a suitable activating solution using either homebuilt instruments or the commercial Glyconeer 2.1 glycan synthesizer.[5]
The resin equipped with linker 5 will produce spacer-free reducible glycans while linker 6 returns glycans with the aminoalkyl spacer and linker 7 produces benzyl-protected glycans at the reducing end

Summary

■ INTRODUCTION

The procurement of complex oligosaccharides in satisfactory quantities and quality as tools for glycobiology remains challenging. The photolytic process depends on the nature of both the leaving groups and the photolabile core.[20] to prepare reducible glycans by AGA, the use of MeNV-type linker 5 or 7 is most efficient. The structural analysis of each compound revealed that the main glycan was acceptor 29 and the minor was its diastereoisomer having an aberrant Man-β(1,3)-Man glycosidic bond with a 1JC,H value of 160 Hz at 95.8 ppm (Figure 5A, circled in red) To support this assignment, AGA of glycan sequence F2GH2E proceeded smoothly to afford the congener tetrasaccharide as the sole product (SI, compound S6). Branched octasaccharides 33 and 34 were isolated in lower quantities because these glycans unexpectedly fragmented during hydrogenation to create mixtures of truncated glycans

■ CONCLUSIONS

■ ACKNOWLEDGMENTS

■ REFERENCES