Synthesis of homo- and heteromultivalent carbohydrate-functionalized oligo(amidoamines) using novel glyco-building blocks

Felix Wojcik,Alexander G O’Brien,Sinaida Lel,Laura Hartmann,Peter H Seeberger

doi:10.3762/bjoc.9.276

Abstract

We present the solid phase synthesis of carbohydrate-functionalized oligo(amidoamines) with different functionalization patterns utilizing a novel alphabet of six differently glycosylated building blocks. Highly efficient in flow conjugation of thioglycosides to a double-bond presenting diethylentriamine precursor is the key step to prepare these building blocks suitable for fully automated solid-phase synthesis. Introduction of the sugar ligands via functionalized building blocks rather than postfunctionalization of the oligomeric backbone allows for the straightforward synthesis of multivalent glycoligands with full control over monomer sequence and functionalization pattern. We demonstrate the potential of this building-block approach by synthesizing oligomers with different numbers and spacing of carbohydrates and also show the feasibility of heteromultivalent glycosylation patterns by combining building blocks presenting different mono- and disaccharides.

Highlights

Multivalent carbohydrate ligand–protein receptor interactions play a key role for many events in glycobiology such as cell–cell or pathogen recognition [1]
We present the solid phase synthesis of carbohydrate-functionalized oligo(amidoamines) with different functionalization patterns utilizing a novel alphabet of six differently glycosylated building blocks
In order to explore the feasibility of the building-block approach for the synthesis of precision glycooligo/polymers, in this work we report on the reaction of several thioglycosides and the double bond presenting diethylenetriamine succinic acid building block (DDS) 1, giving access to a small alphabet of carbohydrate-functionalized building blocks

Summary

Introduction

Multivalent carbohydrate ligand–protein receptor interactions play a key role for many events in glycobiology such as cell–cell or pathogen recognition [1]. Β-GlcNAc and β-Gal are exposed in alternating fashion with an overall oligomer length of six building blocks and a molecular weight of 3000 Da. Similar to glycooligomer 15 this structure was obtained as highly pure material after solid-phase synthesis using HATU activation and HPLC purification.

Results

Conclusion