FTI_Technical_Newsletter

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CEOverture...

I’ve got a 1-month old baby boy at home, and I can’t help but marvel at how quickly he changes and adapts on a daily basis. Fluorous chemistry is only a little more than a decade old (that’s newborn-like in the industrial world!) and many changes in the technology have taken place over that time. This purification-oriented technology, born as a catalyst removal technique, was quickly adapted to high-throughput synthesis of small molecules. More recently the technology has crawled into synthesis, purification and microarraying of biomolecules, which in turn has opened up new opportunities in markets such as biopolymer synthesis and systems biology. Sure, fluorous still has a long ways to go to reach full maturity, but like any parent will tell you- these newborn days go by too quickly. So, sit down, grab a cup of coffee and enjoy a few pics and snippets from the most recent additions to our still growing fluorous family album.

Cheers,

Proud Papa Phil

Philip E. Yeske
President & CEO

QSAR & Combinatorial Science - Special Issue on Fluorous Synthesis

qsar The most up-to-date works in fluorous chemistry are reviewed in a recent special issue of QSAR & Combinatorial Science (2006, 25, 675-806), edited by Dr. Wei Zhang from Fluorous Technologies. This issue has a collection of sixteen articles, including reviews, communications, and full research papers written by diverse groups from around the world. The following topics are included in this special issue:

Fluorous synthesis of small molecules, peptides, oligosaccharides and bioconjugates
Reactions using fluorous catalysts, reagents, scavengers, protecting groups and tags
Fluorous multi-component reactions (MCRs), microwave reactions (MAOS) and diversity-oriented synthesis (DOS)
Fluorous biphasic, triphasic, solid-phase extraction and HPLC separations

To see this issue online, log onto: http://www3.interscience.wiley.com/cgi-bin/jissue/112782272

If you would like to receive a complimentary copy from FTI (while supplies last) please complete a short registration form on our website and indicate “COMPLIMENTARY QSAR” in the Feedback box.

Purification by Fluorous Liquid-Liquid Extraction

Fluorous liquid-liquid extraction (F-LLE) is commonly used for separation of heavy fluorous molecules, whereas fluorous solid-phase extraction (F-SPE) is more suitable for light fluorous molecules. As reported last year, however, solvent tuning can dramatically effect fluorous extraction efficiencies.(1) In a recent paper Prof. Dennis Curran and coworkers applied this concept to develop a fluorous Mitsunobu reaction using F-LLE as the purification method.(2) A biphasic solvent system containing HFE-7100 (C4F9OMe) and FC-72 (perfluorohexanes) as the fluorous phase and 10% water in DMF as the organic phase was used to remove the by-products of fluorous DIAD and fluorous triphenyl phosphine from the reaction mixture. This F-LLE system efficiently removed 98-98.5% of the fluorous components. All solvents and reagents are commercially available. F-LLE is an attractive alternative to F-SPE in many applications, especially those conducted on larger scale. If you are interested in other potential F-LLE applications please contact FTI.

FLLE

Fluorous Synthesis & Purification of Polyamides

Prof. Steven Firestine and Sreeman Mamidyala of Wayne State University recently published a fluorous synthesis of N-methylpyrrole polyamides using a fluorous tag.(3) These and related polyamides are of interest as sequence specific DNA minor groove binding agents. As such, a variety of syntheses using both solid-phase and solution phase methods based on standard peptide chemistry have been reported. Many of these methods, however, suffer from laborious purification protocols. The use of a fluorous BOC group provided a solution phase synthesis with facile purification of intermediates by fluorous solid phase extraction. The f-BOC group was easily removed in high yield using TFA in CH2Cl2, analogous to traditional BOC chemistry. The fluorous synthesis and purification strategy was noted as being superior to conventional methods in easily accessing this interesting and important class of molecules. Prof. Firestine's work nicely demonstrates the advantages and attributes of fluorous chemistry, including solution phase reactivity in combination with simple solid phase-like purification.

firestine

Fluorous-Phase Synthesis of Disubstituted Exo-a-Methylene-Lactones

Alpha-Methylene-gamma-lactones are found in a wide range of natural products. So far there has been only limited effort on synthesis of libraries with this kind of scaffold. The Gouault group at University of Rennes recently developed a fluorous protocol for the parallel synthesis of this important structural motif.(4) In an initial step, a fluorous beta-hydroxy ester was produced by the Baylis-Hillman reaction of a fluorous acrylate and an aldehyde. A dioxanone by-product was also generated and it was easily removed from the desired ester by fluorous solid-phase extraction (F-SPE) using a FluoroFlash® cartridge. Subsequent palladium catalyzed carbonyl allylation lead to the formation of mono- or disubstituted alpha-methylene-gamma-lactones with concomitant removal of the fluorous tag. F-SPE was again employed to separate the final products from the cleaved fluorous alcohol. Twenty five analogs generated from this two-step parallel synthesis were submitted to cytotoxic evaluation on a human melanoma cell line. This work is a good example of the utility of fluorous tags for library synthesis in combination with F-SPE for purification. Reactions can be monitored by conventional tools and intermediates can be easily analyzed by 1H NMR.

gouault

Back-to-School Academic Promotion

promotion cartoon Attention, academicians (and their minions) - here's your chance to take advantage of a great sales promotion on a wide variety of fluorous reagents offered and in the process, see how fluorous chemistry can make your daily work easier and more efficient. Place an order from now through Nov 15 and a 20% discount will be applied to any purchase order of select fluorous reagents; just ask for the “Back-to-School” Promotion when you place your order. Don’t live in the ivory tower any longer? Ask us, and we just might let you go back to school for a day. Wouldn’t that be nice?