Empirical understanding of glycosylation reactions

• Applicant: Professor Dr. Peter H. Seeberger
• Subject Area: Analytical Chemistry ; Organic Molecular Chemistry - Synthesis and Characterisation
• Term: from 2015 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 251124697

Oligosaccharides are ubiquitous in biological systems. The key step to synthesize these complex structures by glycosylation reactions is the coupling of two individual sugar units. The reaction conditions are almost always substrate dependent, significantly delaying any synthetic route. They are highly sensitive two-stage reactions, proposed to first form a reactive acyloxonium ion intermediate which is trapped by the second sugar unit. To date, optimization of these processes occurs exclusively in a manual fashion via analysis of the products obtained. In this project the first automated reaction optimizer for glycosylation reactions will be developed, where the formation of the key reactive intermediate formed upon activation of monosaccharides on a microfluidic platform will be monitored in situ for the first time using Raman spectroscopy. The system will utilize multivariate analysis of the Raman data for characterization of the reaction mixture in position and time. In this way, intermediate basis spectra will be obtained. By controlling the reaction conditions, the concentration of the key reactive intermediate can be maximized at the site where the trapping agent (second sugar) is added. The Raman data will feed into the computer program LabVIEW, which, based on the results received, will automatically control pumps and temperature in order to optimize the chemical processes. Apart from the development of a new characterization approach, this system will give us tremendous insight into how glycosylation reactions work, how reaction conditions and substituents affect the formation of the key reactive intermediate, as well as to the rates of both acyloxonium ion formation as well as intermolecular trapping. This system will transform the way glycosylation reactions are both performed and understood.

• DFG Programme: Research Units
• Subproject of: FOR 2177: Integrated Chemical Micro Laboratories
• Co-Investigators: Dr. Kerry Gilmore, Ph.D.; Professorin Dr. Janina Kneipp