Hierarchical and programmable one-pot synthesis of oligosaccharides

Cheng-Wei Cheng,Wen-Lian Hsu,Chi-Huey Wong,Chung-Yi Wu,Yixuan Zhou,Wen-Harn Pan,Supriya Dey

doi:10.1038/s41467-018-07618-8

Abstract

The programmable one-pot oligosaccharide synthesis method was designed to enable the rapid synthesis of a large number of oligosaccharides, using the software Optimer to search Building BLocks (BBLs) with defined relative reactivity values (RRVs) to be used sequentially in the one-pot reaction. However, there were only about 50 BBLs with measured RRVs in the original library and the method could only synthesize small oligosaccharides due to the RRV ordering requirement. Here, we increase the library to include 154 validated BBLs and more than 50,000 virtual BBLs with predicted RRVs by machine learning. We also develop the software Auto-CHO to accommodate more data handling and support hierarchical one-pot synthesis using fragments as BBLs generated by the one-pot synthesis. This advanced programmable one-pot method provides potential synthetic solutions for complex glycans with four successful examples demonstrated in this work.

Highlights

The programmable one-pot oligosaccharide synthesis method was designed to enable the rapid synthesis of a large number of oligosaccharides, using the software Optimer to search Building BLocks (BBLs) with defined relative reactivity values (RRVs) to be used sequentially in the one-pot reaction
The software Auto-CHO contains three unique features: (1) the program can be operated by graphical user interface and is a cross-platform with Java Runtime Environment; (2) it provides more synthetic BBLs with validated RRVs, and virtual BBLs with accurately predicted RRVs to greatly expand the current library size; (3) the program can be used to guide the one-pot synthesis of more complex oligosaccharides through fragment coupling
The structures of these virtual BBLs may not have been synthesized previously, most of them were used in glycosylation reactions with different leaving groups, so we can leverage many of the existing BBLs with different leaving groups which have been used for glycosylation reactions and convert them to thioglycosides or incorporate them into the program directly to increase the number of potentially feasible combinations

Summary

Introduction

The programmable one-pot oligosaccharide synthesis method was designed to enable the rapid synthesis of a large number of oligosaccharides, using the software Optimer to search Building BLocks (BBLs) with defined relative reactivity values (RRVs) to be used sequentially in the one-pot reaction. We develop the software Auto-CHO to accommodate more data handling and support hierarchical one-pot synthesis using fragments as BBLs generated by the one-pot synthesis This advanced programmable one-pot method provides potential synthetic solutions for complex glycans with four successful examples demonstrated in this work. The programmable one-pot synthesis method was developed to tackle this problem and was based on the sequential use of thioglycoside BBLs to form glycosidic bonds according to the reactivity differences of the BBLs4. The user can decide which combination of BBLs to use, based on their knowledge and the availability of BBLs. The original Optimer program could only synthesize small oligosaccharides due to the RRV ordering requirement, and the limited number of BBLs. To make glycan synthesis more versatile and applicable to more complex oligosaccharides as well as available to the research community, we develop a software called Auto-CHO to meet the challenges encountered in the original Optimer program

Methods

Results

Conclusion