Programmable One-Pot Oligosaccharide Synthesis

TLDR

The study aims to develop a broadly applicable one‑pot synthesis of oligosaccharides by quantitatively determining the reactivity of various p‑methylphenyl thioglycoside donors. Reactivity of fully protected and partially exposed p‑methylphenyl thioglycoside donors was quantified by HPLC. The authors quantified how monosaccharide cores and protecting groups affect donor reactivity, linked reactivity to anomeric NMR shifts, built a thioglycoside donor database, and demonstrated its use for rapid one‑pot assembly of linear and branched oligosaccharides, supported by the OptiMer computer program.

Abstract

In an effort to develop a broadly applicable approach to the facile one-pot synthesis of oligosaccharides, the reactivity of a number of p-methylphenyl thioglycoside (STol) donors which are either fully protected or have one hydroxyl group exposed has been quantitatively determined by HPLC. We have characterized and quantified the influence on reactivity of the structural effects of different monosaccharide cores and different protecting groups on each glycoside donor. In addition, we have established a correlation between glycosyl donor reactivity and the chemical shift of the anomeric proton by 1H NMR. Using the reactivity data, we have created a database of thioglycosides as glycosyl donors and demonstrated its utility in the easy and rapid one-pot assembly of various linear and branched oligosaccharide structures. In addition, we have developed the first computer program, OptiMer, for use as a database search tool and guide for the selection of building blocks for the one-pot assembly of a desired oligosaccharide or a library of individual oligosaccharides.