If your email does not support graphics, please access the web version of this technical bulletin.   contact button Contact FTI

 

 

CEOverture...

As 2007 draws to a close, we are taking a moment in this month’s newsletter to highlight major advancements in the fluorous field from the past year. We’ll also give you a first peek at 2008, including a great chance to get the jump on a more productive new year by taking advantage of a year-end discount opportunity (for those of you with a soon-to-be-gone supplies budget that needs to be spent pronto- you know who you are).

 

Happy Holidays to all of you!

Phil

Philip E. Yeske
President & CEO

   

Small Molecule and Library Synthesis:

 

Since the publication of the first fluorous-based separation that combined a fluorous tagged molecule with a fluorous modified silica gel, this technique has found widespread application in a number of fields.  Fluorous Technologies Inc. (FTI) began commercializing FluoroFlash® products in 2003 and since that time the utility and robustness of fluorous separations have been demonstrated in labs around the world. During 2007 we saw the continued development of new reagents, tags, and separation techniques for small molecule synthesis and purification.  Many of these advancements were directed toward parallel synthesis efforts.  For instance, FTI scientists have developed a high-throughput fluorous solid phase extraction (F-SPE) technique using a 96-well plate format.[1] This gravity-driven F-SPE employs a larger particle size FluoroFlash® silica gel to overcome potential problems with variable flow rates between wells.  A water-free F-SPE process associated with the 96-well plate was also introduced.  Another method by which to increase throughput is fluorous mixture synthesis (FMS).  Several papers including one from the Crich group[2] and one from Mikami and Tonoi[3] described new approaches to FMS. 

 

New reagents, scavengers, and tags have also been introduced this year expanding the number of synthetic options.  Some of the more interesting ones include a new fluorous carbodiimide[4], a fluorous Mukaiyama’s salt for amide bond formation[5], and a number of fluorous organocatalysts for epoxidations[6], imine reductions[7], and zincate additions[8].  Various research groups have used these and other fluorous reagents in 2007 for library production, total synthesis, and even for natural products isolation.  The work highlighted above along with many others in 2007 continues to demonstrate the value of fluorous techniques in small molecule preparation and to push fluorous chemistry into new arenas.  For a complete set of references including a downloadable EndNotes file, please visit the references page at www.fluorous.com. 

 

Peptide, Carbohydrate, and Oligonucleotides:

Fluorous techniques have been shown to be valuable tools in the synthesis and purification of peptides, oligosaccharides, and oligonucleotides either as an alternative or as a complement to solid supported synthesis.  This year saw the continued development of fluorous techniques in the synthesis of these oligomeric compounds, particularly with respect to carbohydrate synthesis.  Professor Seeberger at the ETH published two papers this year using fluorous techniques.  The most recent reported using a fluorous tagging strategy in the solid phase synthesis of oligosaccharides, where a fluorous silane was attached at the terminus of the completed oligosaccharide.[9]  Earlier in the year, they described a microreactor based solution phase synthesis of oligosaccharides using a fluorous tag.[10]  Meanwhile in Japan, Prof. Takeuchi at Niigata University has used a fluorous benzylidene acetal for the synthesis of disaccharides.  In all of the above cases, fluorous solid phase extraction (F-SPE) was used as the fluorous separation method.  Fluorous liquid-liquid extraction can also be used, however, as Prof. Mizuno at the Noguchi Institute has shown in the preparation of oligosaccharides and carbohydrate monomers.[11]  As all of this work indicates, fluorous chemistry is finding increased use in the synthesis of bio-oligomeric molecules.  For additional references and details, please visit our webpage describing the various fluorous strategies for the synthesis of peptides, oligosaccharides, and oligonucleotides.

 

Fluorous at the Interface of Chemistry and Biology:

Fluorous techniques continued to advance beyond just synthesis and to the burgeoning areas of chemical biology, metabolomics, and proteomics as researchers take advantage of the unique separation properties of fluorous tags.  As mentioned in previous newsletters and in F-Blog, the formation and validation of small molecule microarrays on FluoroFlash® modified glass slides as described in two separate publications by Spring et al[12] and Schreiber et al[13] was an important milestone in fluorous applications.  Another important paper was the use of a fluorous modified porous silicon surface for on-target enrichment and MS detection of fluorous tagged molecules from biologically derived samples.  In this work, Prof. Suizdak and co-workers at The Scripps Research Institute were able to fluorous tag specific classes of molecules, for example peptides from a protein digest and amino acids from serum, in a given sample.[14] Spotting onto a fluorous modified surface was followed by washing to remove non-tagged components and direct detection by desorption/ionization on silicon mass spectrometry (DIOS-MS).  Meanwhile, here at Fluorous Technologies, we are working with our collaborators at the Genomics Institute of the Novartis Research Foundation on developing new fluorous tagging reagents and protocols for quantitative proteomics. 

 

2007 Events and Awards

The biggest event for 2007 was the 2nd International Symposium on Fluorous Technologies (ISoFT’07) which was held in Yokohama, Japan this summer.  ISoFT’07 brought together many of the world’s leading researchers in fluorous chemistry and included a variety of speakers and topics ranging from supramolecular assemblies to synthesis to catalysis to biological sensors.  To read more about ISoFT’07 you can visit F-Blog for the daily reports.  Fluorous chemistry was also in the spotlight at the 234th ACS National Meeting in Boston where the Division of Fluorine Chemistry sponsored a symposium on fluorous nanostructures.  ISoFT’07 was highlighted by the presentation of the Fluorous Technologies Award to Dr. John Gladysz and the Noguchi Award to Dr. Dennis Curran for their outstanding contributions to fluorous chemistry.  In addition to the Noguchi Award, Dr. Curran will be the 2008 recipient of the ACS Award for Creative Work in Fluorine Chemistry which he will receive at next spring’s ACS National Meeting in New Orleans.  Congratulations to both Drs. Gladysz and Curran for their many contributions and well deserved awards.

 

Want to Get Started in 2008?

Are you intrigued by the potential of fluorous techniques and want to learn more?  There are several ways to learn more beyond scouring the available literature or the references listed above.  You can visit our website to view and download application notes, references, and presentations which describe various fluorous applications.  Another valuable resource is the Sigma-Aldrich Cheminar® on fluorous chemistry and techniques.  The Cheminar® is an online educational seminar that was produced in conjunction with FTI and provides an excellent overview for those interested in “light” fluorous applications utilizing FSPE.  Finally, contact FTI directly! Email or call us (412-826-3050) and we will be happy to answer any questions that you may have. 

 

In order to lower the barrier to getting started we are currently offering 30% off all orders of selected reagents (listed below) through January 15, 2008 when a Fluorous Sorbent is included in your order. If you don't see the fluorous reagent(s) that you are interested in on this list, give us a call at 412-826-3050- we're ready to strike deal if you are.

Fluorous Reagents Including:
Fluorous Iodide Family: Perfluoroalkyl Iodides Ethyl Iodides Propyl Iodide F013002
Fluorous Alcohol Family: Benzyl Alcohol F013026 Propanol F017029

       Ethanol          F013077

   t-Butanol   F015007
Fluorous Bromobenzene Family: Bromobenzene (branched) Bromobenzene (ethylene spacer)
 
     Fluorous Thioacetate    F009022 - F017022
           Fluorous Olefins             F013034 - F017034 - F019034
F-Cbz-Osu - F017008
F-Trichlorosilane - F017230

    F-Triphenylphosphine (F-TPP)

 

Whether your research entails synthesis, analysis, or materials fluorous can help increase your research productivity. 

 

What's Planned at FTI for 2008?

 

With 2007 winding down, it’s time to look forward to what lies in store for 2008.  FTI planned activities include:

  • Production of small molecule libraries through a NIH Pilot Scale Libraries grant leading to novel chemical scaffolds and synthetic strategies.
  • Demonstration of an enzyme activity assay on a fluorous microarray format
  • Development of new reagents and protocols for quantitative proteomics
  • Introduction of a completely new FTI website for easier navigation and more up to date content
  • Increased frequency of F-Blog posts

 

References Cited:

1.  Zhang, W.; Lu, Y. J. Comb. Chem. 2007, 9, 836-843.

2. Crich, D.; Grant, D.; Bowers, A. A. J. Am. Chem. Soc. 2007, 129, 12106-12107.

3.  Tonoi, T.; Mikami, K. Eur. J. Org. Chem. 2007, 1730-1733.

4.  del Pozo, C.; Keller, A. I.; Nagashima, T.; Curran, D. P. Org. Lett. 2007, 9, 4167-4170.

5.  Matsugi, M.; Hasegawa, M.; Sadachika, D.; Okamoto, S.; Tomioka, M.; Ikeya, Y.; Masuyama, A.; Mori, Y. Tetrahedron Lett. 2007, 48, 4147-4150.

6.  Cui, H.; Li, Y.; Zheng, C.; Zhao, C.; Zhu, S. J. Fluorine Chem. 2007, DOI:10.1016/j.jfluchem.2007.08.012.

7.  Malkov, A. V.; Figlus, M.; Stoncius, S.; Kocovsky, P. J.Org. Chem. 2007, 72, 1315-1325.

8.  Sokeirik, Y. S.; Mori, H.; Omote, M.; Sato, K.; Tarui, A.; Kumadaki, I.; Ando, A. Org. Lett. 2007, 9, 1927-1929.

9.  Carrel, F. R.; Seeberger, P. H. J. Org. Chem. 2007,DOI: 10.1021/jo701349c.

10. Carrel, F. R.; Geyer, K.; Codee, J. D. C.; Seeberger, P. H. Org. Lett. Org. Letters 2007, 9, 2285-2288.

11. Goto, K.; Mizuno, M. Tetrahedron Lett. 2007, 48, 5605-5608.

12. Nicholson, R. L.; Ladlow, M. L.; Spring, D. R. Chem. Commun. 2007, 3906-3908.

13. Vegas, A. J.; Bradner, J. E.; Tang, W.; McPherson, O. M.; Greenberg, E. F.; Koehler, A. N.; Schreiber, S. L. Angew. Chem., Int. Ed. 2007, 46, 7960-7964.

14. 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, 1492-1499.

 

contact button Anytime you are on the web and need further information, just click on the "Contact Us" button located on the top corner of each page. Here you will find phone, fax and email contact information.