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CEOverture...
For sure one of the most exciting aspects of fluorous technology is the breadth of applications to which it can be applied. For instance, what do on-surface enrichment, catalyst recovery and combinatorial chemistry have to do with each other? Not much, except that in today’s newsletter we highlight a few examples from the recent literature that demonstrate the use of fluorous tags in each of these applications, all of which take advantage of facile fluorous separation. In general, if you’ve got a material of high value (or, at least, that YOU highly value) that needs to be separated from a complex mixture, chances are that a fluorous separation technique can help you out. We love discussing out-of-the box ideas that play upon this value proposition, so just drop a line if you think you’ve got a new one to share.
Cheers,
Phil
Philip E. Yeske
President & CEO
On-Target Fluorous Enrichment & MS Analysis
Researchers from Scripps Research Institute and the Genomics Institute of the Novartis Research Foundations (GNF) led by Gary Siuzdak and Eric Peters recently reported the use of fluorous tags in the on-surface enrichment of specific molecular subsets and direct MS analysis using desorption/ionization on silicon MS (DIOS-MS).[1]
A subset of a mixture of peptides or small molecules was fluorous tagged and then deposited onto a fluorous modified porous silica surface. Washing of the surface with the appropriate fluorophobic solvent, such as 50% aqueous MeOH, resulted in selective enrichment of the fluorous tagged compounds on the surface which were then analyzed by DIOS-MS. Fluorous tagging agents investigated included fluorous alcohols, amines and thiols which were each used to target specific functionalities. The research culminated in the fluorous DIOS-MS analysis of esterified carboxylic acid containing moieties found in human serum. Compared to standard esterification, the fluorous method demonstrated increased sensitivity presumably due to the facile removal of non-tagged endogenous metabolites by the fluorous enrichment. This report powerfully demonstrates the effectiveness of fluorous techniques for the enrichment of specific molecules from complex biological samples and the compatibility of fluorous tags with modern MS-based analytical methods.
Reference:
1. Go, E.P.; Uritboonthai, W.; Apon, J.V.; Trauger, S.A.; Nordstrom, A.; O’Maille, G.; Brittain, S.M.; Peters, E.C.; Siuzdak, G. J. Proteome Res., 2007, 6, 149.
Fluorous Crown Ethers as Phase-Transfer Catalysts
In a recent publication[1] Stuart and Vidal reported the synthesis of three different crown ethers containing two fluorous side chains (Rf) by N-alkylation of 4,13-diaza-18-crown-6 with fluorous iodides. These fluorous crown ethers have been tested as phase-transfer catalysts (PTCs)
in classic nucleophilic substitution reactions including conversion of a primary bromide to an iodide using KI and substitution of an aromatic chloride with a fluoride using KF. In each case, the fluorous PTCs have similar catalytic activity compared to the parent nonfluorinated PTC, but with the added benefit of facile removal and recovery by fluorous solid-phase extraction.[2] The authors further demonstrated that the fluorous PTCs can be recycled up to six times without any loss in activity. Once again, fluorous techniques were found to be a valuable method by which an inert chemical handle could be incorporated into a molecule for easy recovery.
References:
1. Stuart, A. M.; Vidal, J. A. J. Org. Chem. 2007, 72, 3735-3740.
2. Zhang, W.; Curran, D. P. Tetrahedron 2006, 62, 11837–11865.
Fluorous Synthesis of Novel Heterocyclic Compound Library
At the recent CHI Meeting “High-throughput Organic Synthesis & Purification” in San Diego, Dr. Stefan Werner, Assistant Director of the University of Pittsburgh Center for Chemical Methodologies & Library Development (CMLD), presented a talk featuring the fluorous synthesis of a novel heterocyclic scaffold containing piperazinedione. Over 100 compounds with R1 to R4 substitution variation were made by solution-phase parallel synthesis. A fluorous propyl alcohol was used as the tag for simple intermediate purification by fluorous solid-phase extraction (F-SPE). The final products were purified by HPLC. Greater than 90% of the planned library met the required purity and quantity (50 mg) specifications. Dr. Werner noted that the use of fluorous techniques undoubtedly increased overall productivity and allowed a greater number of compounds to be produced in the allotted project time. FTI provides numerous types of fluorous tags which have been used in the synthesis of various heterocycles and natural product-like compounds.[1] Fluorous tags in conjunction with fluorous separation techniques can increase your efficiency, just as it did for the Pitt CMLD- give it a try!
Reference:
1. Zhang, W. Comb. Chem. High Throughput Screening 2007, 10, 219-229.
Introducing the Fluorous Blog
FTI is pleased to announce a new feature to our website, the F-Blog. This blog will be dedicated to serving the fluorous community by providing a forum about events, advancements, literature reports, and ideas related to fluorous techniques. The F-Blog complements our electronic Newsletter by providing a continuous source of fluorous news and by providing a method for public feedback, not available through the Newsletter. At the same time, we hope that the F-Blog will be fun by providing researchers a vehicle by which to express opinions, successes, failures, and ideas regarding fluorous techniques. (Note: As the blog administrator, FTI will moderate comments for the purpose of keeping discussions on topic and non-offensive, but we do plan to post all appropriate feedback, warts and all. What good is a blog without some controversy?)
The FTI staff will be providing regular posts (at least 2-3/week) to keep the blog fresh and interesting. As part of our efforts to build a community and provide a voice, we invite you to contribute with comments or posts and to subscribe to F-Blog via a RSS or Atom feed, so that you will know when a new entry has been posted. Need help setting that up? We can help. Please join us in making this new forum a success.
ISoFT'07 Meeting - See you in Japan!
FTI is a proud corporate sponsor of the 2nd International Symposium on Fluorous Technologies, to be held July 29-August 1, 2007 in Yokohama-Kamakura, Japan. An impressive agenda of speakers will bring all attendees up-to-speed on the latest fluorous developments in diverse fields such as organic synthesis, catalysis, polymers, supramolecular chemistry and biological applications. FTI is more than just a sponsor- we’ll also have a speaker and an exhibit table on-hand. Stay tuned for more details on the conference in next month’s newsletter.