Fluorous Oligomer Synthesis
Scalable solution-phase approach with simple separation
Methods of Use
Solid Phase Extraction
Oligosaccharide Synthesis
A method published by Seeberger, P.H. et al describes the synthesis of oligosaccharides incorporating fluorous chemistry. In this case, the fluorous portion is a "cap-tag", which is used to render the undesired material fluorous, while the desired oligomeric species is non-fluorous. Fluorous HPLC is used to separate the fluorous material from the non-fluorous material and obtain the desired material in pure form. Two new fluorous tags are described for use in this process.[1]
Fluorous Silyl Ethers
Manzoni, in a new method, describes the use of a fluorous silyl ether tag as a protecting group to allow the rapid synthesis of oligosaccharides. Using this method, he reduces the purification procedures to a simple and fast fluorous solid-phase extraction.[2]
The acid and base-stable silyl protecting group is appended to the anomeric position of glycosyl acceptors in a growing oligosaccharide chain. The glycosyl acceptor bound to the fluorous tage can be coupled with the glycosyl donor to afford the fluorous disaccharide which is separable from non-fluorous material, such as excess donor, by solid-phase extraction without the need for column chromatography. The reaction mixture is passed through fluorous silica gel in a two-stage extraction, which is first removes the non-tagged products, then elutes the fluorous-tagged product. The fluorous tag is removed at the end of the synthetic sequence to give the desired oligosaccharide. This method avoids the tedious, expensive, and time consuming flash chromatography purification of the reaction product after every step.
Liquid-Liquid Extraction
In the publications cited below, the solid-support has been substituted with a fluorous support rendering all the chemistry solution phase and allowing for complete reaction monitoring. The filtrations between reactions has been replaced with simple liquid-liquid extractions.
Fluorous Protecting Groups
Miura, T., Y. Hirose, et al. (2001). "Fluorous oligosaccharide synthesis using a novel fluorous protective group." Org Lett 3 (24): 3947-3950.
Miura, T. and T. Inazu (2003). "Rapid synthesis of oligosaccharide moieties of globotriaosylceramide using fluorous protective group." Tetrahedron Letters 44 (9): 1819-1821.
Abstract: The use of the Bfp (bisfluorous chain type propanoyl) group as a fluorous protective group made it possible to rapidly synthesize galabiose and the Gb3 oligosaccharide derivs. by a simple fluorous-org. extn. purifn. The fluorous oligosaccharide synthesis using the Bfp group is an excellent strategic alternative to solid phase oligosaccharide synthesis, and removes some of the disadvantages of the solid phase method.
Fluorous Peptide Synthesis
Mizuno, M., T. Miura, et al. (2003). "A novel peptide synthesis using a fluorous chemistry." Peptide Science 39th : 147-150.
Abstract: Three new fluorous supports for peptide synthesis, i.e., the trialkoxybenzhydryl-type (6), the Wang-type (7) and the tent-butyl-type support (8), were prepd. A bioactive peptide TRH was easily synthesized by an Fmoc-strategy using the benzhydryl-type fluorous support with fluorous chem.
Fluorous Oligosaccharide Synthesis
Miura, T., K. Goto, et al. (2003). "Oligosaccharide synthesis on a fluorous support." Angewandte Chemie, International Edition 42 (18): 2047-2051.
Mizuno, M., K. Goto, et al. (2003). "A novel peptide synthesis using fluorous chemistry." Chemical Communications (Cambridge, United Kingdom) (8): 972-973.
Abstract: Three new fluorous supports for peptide synthesis, i.e., the trialkoxybenzhydryl-type (6), the Wang-type (7) and the tert-butyl-type support (8), were prepd. A bioactive peptide TRH was easily synthesized by an Fmoc strategy using the benzhydryl-type fluorous support with fluorous chem.
Selected References
- Palmacci, E. R.; Hewitt, M. C.; Seeberger, P. H. 'Cap-Tag' - novel methods for the rapid purification of oligosaccharides prepared by automated solid-phase synthesis Angew. Chem. Int. Ed. 2001 , 40, 4433.
- Manzoni, Leonardo. Rapid synthesis of oligosaccharides using an anomeric fluorous silyl protecting group. ChemComm (The Royal Society of Chemistry), 2003, 2930-2931.