Hplc-based oligosaccharide synthesis: entirely automated glycan assembly

S4.3 Synthetic innovation in glycan assembly
Location (hall): 
Start/end time: 
Tuesday, July 2, 2019 - 12:00 to 12:15

Matteo Panza1, Keith Stine1, Alexei Demchenko1

1University Of Missouri St. Louis, St. Louis, United States

Since the introduction of solid supported synthesis of oligosaccharides in the last century [1], the field has seen a substantial progress with the development of automated devices [2]. The HPLC based system, developed by Demchenko and Stine [3], was upgraded with the implementation of an autosampler allowing for the automated delivery of the promoter for glycosylation reaction [4]. Despite that, the system still lacked the components for full automation.

Presented herein is the introduction of a new computer operated split-valve module and a programmable autosampler in the design of fully automated synthetic sequences (Figure 1a). 

Simple programs have been written and combined into more sophisticated sequences to build target glycans (Figure 1b). All the reagents are delivered automatically through the autosampler while the quaternary pump delivers the solvents necessary for the reactions.

Figure 1. (a) HPLC-based synthesizer equipped with split valve and (b) target glycans

  1. Panza, M.; Pistorio, S. G.; Stine, K. J.; Demchenko, A. V., Automated Chemical Oligosaccharide Synthesis: Novel Approach to Traditional Challenges. Chemical Reviews 2018, 118 (17), 8105-8150.
  2. Krock, L.; Esposito, D.; Castagner, B.; Wang, C.-C.; Bindschadler, P.; Seeberger, P. H., Streamlined access to conjugation-ready glycans by automated synthesis. Chem. Sci. 2012, 3, 1617-1622.
  3. Vijaya Ganesh, N.; Fujikawa, K.; Tan, Y. H.; Stine, K. J.; Demchenko, A. V., HPLC-assisted automated oligosaccharide synthesis. Org. Lett. 2012, 14, 3036-3039.
  4. Pistorio, S. G.; Nigudkar, S. S.; Stine, K. J.; Demchenko, A. V., HPLC-Assisted Automated Oligosaccharide Synthesis: Implementation of the Autosampler as a Mode of the Reagent Delivery.The Journal of Organic Chemistry 2016, 81 (19), 8796-8805.