Fluorous Mixture Synthesis: A Fluorous-Tagging Strategy for the Synthesis and Separation of Mixtures of Organic Compounds

Abstract

The solution-phase synthesis of organic compounds as mixtures rather than in individual pure form offers efficiency advantages that are negated by the difficulty in separating and identifying the components of the final mixture. Here, a strategy for mixture synthesis that addresses these separation and identification problems is presented. A series of organic substrates was tagged with a series of fluorous tags of increasing fluorine content. The compounds were then mixed, and multistep reactions were conducted to make enantiomers or analogs of the natural product mappicine. The resulting tagged products were then demixed by fluorous chromatography (eluting in order of increasing fluorine content) to provide the individual pure components of the mixture, which were detagged to release the final products.

Ruthenium-Catalyzed Azide Alkyne Cycloaddition Reaction: Scope, Mechanism, and Applications

“…234 Macrocycles of a non-peptidic nature are often difficult to prepare and are thus not well represented in compound collections employed for pharmaceutical screening purposes. Azido building blocks, of different geometries and containing a fluorous tag to facilitate purification 235 were constructed and then coupled, not using cycloadditions, but via aza-Wittig-type reactions. The RuAAC and CuAAC reactions were instead reserved for the final macrocyclization step, constituting the pair phase.…”

Comparison of the structures and stabilities of coiled‐coil proteins containing hexafluoroleucine and t‐butylalanine provides insight into the stabilizing effects of highly fluorinated amino acid side‐chains

“…This idea is predicated upon the unusual phase-segregating properties of perfluorocarbon solvents, which selectively extract highly fluorinated small molecules from organic solvents into the perfluorocarbon solvent. 36,37 Our previous analysis of the structure of a 4 F 3 a revealed no evidence that contacts between fluorocarbon residues are more stabilizing than contacts between hydrocarbon residues, once differences in buried surface area are accounted for. In the present study we have extended our investigation to examine the interactions of hFLeu in two different packing arrangements, one that introduces hFLeu in only ''d'' positions (a 4 F 3 d) and another that introduces hFLeu in alternating ''a'' and ''d'' positions.…”

Fluorous parallel synthesis of a hydantoin/thiohydantoin library

“…Since the early development by the Curran group in the late 1990's, light fluorous synthesis has quickly become an active research area. The fluorous tagging strategy has been introduced to make reagents [8][9][10][11], scavengers [12][13][14][15][16], protecting groups [17][18][19][20][21] and related tags [22][23] for parallel and mixture syntheses [24][25][26][27][28]. It has also been used in peptide and oligosaccharide syntheses [29][30][31].…”