REEL Organic Chemistry at OSU

Several different Organic Chemistry Reseach Modules have been designed and implemented at OSU, a reflection of the varied research interests of faculty and staff that teach these REEL courses.  One of the most successful modules, developed by Dr. Chris Callam, began with the realization that oligosaccharides are key players in a large number of important biological events that have generated much interest in their preparation by organic synthesis. Motivation for the synthesis of oligosaccharides (both naturally occurring as well as modified analogues) can be found in a number of areas, including biochemical studies and the investigation of anti-cancer vaccines.  The research module, therefore, had students investigate the synthesis of carbohydrates by a novel procedure employing fluorous tagging.

In this investigation, members of a series of substrates (S¹-Sⁿ) are tagged with the corresponding series of homologous fluorous tags (F¹-Fⁿ).  Each fluorous tag bears the same reacting functionality, but the tags differ in a series of homologous series of fluoroalkyl groups. This difference controls the final separation.  The tagged substrates (S¹F¹-SⁿFⁿ) are mixed to give one mixture (M1) that is then taken through a series if synthetic reaction where the economy of the mixture is harvested (the number of operations required at each stage is divided by the number of tags). The mixture synthesis steps can be either one-pot reactions to give new mixtures for example (M2->M3) or split-parallel reaction with a series of building blocks to generate a number of new mixtures for example (M3-> M₁⁴…M_x4).  The one pot mixture reaction is an “internal parallel” approach with no change of library size, while the split –parallel mixture reaction proceeds in “double parallel” fashion that has powerful library amplification capability.   Just prior to detagging, the products are “demixed” (separated) by fluorous chromatography.  This separates the molecules, which elute in order of increasing fluorine content of tag. The chromatography serves both to separate the mixture components and to identify the products.  Detagging provides a total of nx number of final products (P₁¹-P_xⁿ).  Finally, this mixture synthesis approach is scalable and has been used to construct small libraries of relevant products.

Within this module students receive advanced training in spectroscopy, chromatography, solid phase extraction, and fluorous separation chemistry along with preparatory lab experiments.  Students have synthesized fluorous tagged donors and treated with acceptors under standard glycosylation reaction conditions to prepare oligosaccharides.  Several new compounds have been synthesized and characterized by NMR spectroscopy, mass spectrometry, and infrared spectroscopy. As with the other REEL modules used at OSU, this one has also resulted in a very large number of student research posters at local and regional conferences.