Another calendar year has gone by and it’s time that we conduct our annual look back on the year that was.  2011 was another year that saw major advances in the application of fluorous methods in chemical, biological, and materials sciences.   In this newsletter we review some of the more exciting advances reported over the last year in fluorous research, highlighting just how far the science has advanced.

It’s now been a decade since Fluorous Technologies Inc. began operations and in that time the application of fluorous methods has gone well beyond anything we could have imagined.  What started as a novel method for small molecule synthesis and purification has developed into a powerful general method for the separation, enrichment, and immobilization of various classes of molecules from many different chemical and biological matrices.   These advances are a true testament to not only the strengths and breadth of the technology, but also to the inventiveness and ingenuity of the scientific community.   We thank you for your support throughout 2011 and look forward to your (and our!) continued success with fluorous in 2012.

Cheers,

Philip E. Yeske
President & CEO
Fluorous Technologies Inc.

Fluorous Labeling for Enrichment

Fluorous tagging for the enrichment of specific molecular subsets from biologically derived mixtures was first described by Peters et al in 2005 .  Since that time there have been numerous reports describing fluorous-based enrichment of peptides, glycosphingolipids, amino acids, and other classes of molecules. This past year saw more examples of this as new strategies for fluorous enrichment were reported.

Peptide Enrichment

One was the use of fluorous iodoacetamide for the tagging and fluorous enrichment of thiophosphorylated peptides. Thiophosphorylation is used as a surrogate for phosphorylation in the study of kinases since the thiophosphoryl group is a poor substrate for phosphatases.  After tagging, FluoroFlash® NuTips were used to conduct a fluorous solid phase extraction (FSPE). In this example, Prof. David Mann and co-workers initially used biotin as the enrichment tag but realized that endogenous biotinylated proteins would complicate matters.  They then turned to fluorous tags which proved effective in separating the fluorous tagged thiophosphorylated peptide from non-tagged peptides.

Metabolite Enrichment

Another example of fluorous labeling was published by Nohta et al where they used a fluorous isocyanate to detect eight biogenic amines from human urine samples.  Proteins and other water soluble materials were first removed from the samples. After tagging the samples were subjected to fluorous HPLC where eight biogenic amines were easily detected by UV while non-tagged components were eluted with the solvent front.  This work provides a demonstration of how fluorous tagging can be used in metabolomics studies to detect a specific class of metabolites.

Trifunctional Reagents

Also in 2011 the Lo group from City Univeristy of Hong Kong published their work in developing trifunctional reagents containing a protein labeling group, a luminescent tag, and a fluorous tag.  The researchers demonstrated that the rhenium based fluorous thioisocyanate reagent was able to label peptides and that the fluorous tagged peptide could be separated from non-labeled peptides by FSPE. They also showed that the trifunctional reagent was taken up by cells, concentrated in the mitochondria, and visualized by confocal microscopy.  The authors foresee the use of such reagents in the identification and isolation of intracellular receptors.

Advances in Fluorous Oligosaccharide Chemistry and Glycomics

As has been documented for some time now, one of the best applications to date of fluorous methods has been in oligosaccharides, either in synthesis or in analysis, and 2011 saw continued development in this area buoyed by the rising glycomics tide.  In the area of synthesis new methodologies and new protecting groups for fluorous oligosaccharide synthesis were reported during the last 12 months.  An example was published by Takahashi and co-workers at Tokyo Institute of Technology who developed a new fluorous tag for use in one-pot oligosaccharide synthesis.

Chemoenzymatic Synthesis

Another method for oligosaccharide synthesis is enzyme mediated synthesis which eliminates much of the protection and deprotection schemes necessary in regular chemical synthesis.  A good example of this from 2011 were the chemoenzymatic synthesis of heperan sulfates from Liu’s group at the University of North Carolina.  Beyond just the synthesis and purification, the fluorous tag also was invaluable in the MS/MS analysis of the product.  One of the advantages of using fluorous tags is that the tag is non-fragmentary. This means that MS/MS spectra are not complicated by the presence of the tag and that clear, easily interpretable mass shifts in fragments occur.

Immobilization of Oligosaccharides

Fluorous tags can also be used for the immobilization of oligosaccharides as demonstrated by Northen et al earlier this year. The researchers used fluorous tagged oligosacchride substrates to probe environmental samples for glycoside hydrolase activity.  This was done by conducting reactions in a microtiter plate well then spotting an aliquot of the reaction onto a fluorous NIMS surface in order to effect a fluorous immobilization.  All the reaction components could be washed away leaving only the fluorous tagged substrates and products on the fluorous surface.  Laser irradiation of the aliquot spot from the NIMS surface than provided a direct MS readout of the reaction.   The authors were able quickly and quantifiably assess glycoside hydrolase activity in various samples.

Alternative Fluorous Separation and Immobilization Media

Fluorous separations and immobilizations rely on the partitioning of fluorous tagged compounds into a fluorous phase.  At the onset of fluorous chemistry that phase was a perfluorocarbon liquid.  By the late 90′s a solid fluorous phase in the form of fluorous silica gel were developed. In 2005 alternative fluorous liquid phases were introduced through the use of hydrofluoroethers.   Fluorous modified glass slides for immobilization of fluorous tagged molecules was introduced around that same time.  The development of new fluorous separation and immobilization media remains an active area of research and 2011 saw significant advances within this area.

Fluorous Monolith Columns and Microstructured Tubes

Prof. Richard Oleschuck’s group at Queen’s University in Canada published two papers this year describing new fluorous solid phases.  The first was a fluorous polymer monolith column which they then tested in the separation of compounds tagged with varying length fluorous chains.  The separations were as expected with longer fluorous tags being retained longer on the column.  Monolithic columns have several advantages over spherical particle based columns including lower back pressures and void volumes.  These are particularly important in smaller scale separations that are typical for biological separations.

The second was fluorous modified microstructured tubes.  The authors took silica microstructured tubes and fluorous modified the channels then conducted a fluorous separation and achieved a fluorous separation once again based on overall fluorine content.  Both of these reports represent possible alternatives to fluorous silica packed HPLC columns and once fully optimized would have advantageous physical and performance characteristics.

PTFE Filters for Oligosaccharide Immobilization

A third report  late this year of an alternative fluorous solid phase from comes from Prof. Mamoru Mizuno at the Noguchi Institute.  In this instance they used a polytetrafluoroethylene (PTFE) filter to immobilize fluorous tagged oligosaccharides.  The binding of lectins and hemmaglutinin, including the detection of influenza A, was demonstrated.  PTFE has been previously shown by Gladysz to effectively capture fluorous catalysts from reaction mixtures, but this is the first example of fluorous immobilization of a large protein-ligand complex on such a surface.  Given the wide array of PTFE materials available (fibers, sheets, beads, membranes, etc.) the immobilization of ligands and substrates on PTFE provides a range of opportunities.

End of Year Discounts on Bulk FluoroFlash® Silica and Fluorous Modified Glass Slides

FluoroFlash® Silica Gel 15% off 100g and 1 kg quantities

For an extremely limited time only, we are pleased to offer a 15% discount on 100g and 1kg quantities of bulk 40 µm FluoroFlash® silica gel (Part # 801-0100B and 801-1000B).  We rarely offer discounts on silica gel products so this is your chance to stock up at a reduced price.  To receive the discount, orders must be received by Friday December 16th, 2011.  Contact us to place your order and lock in the best FluoroFlash® gel price of the year.

Fluorous Modified Glass Slides $20 off per box

As an end-of-year discount we are now offering the bar-coded fluorous modified slides at $20 off the regular price.  A box of 10 slides (catalog #850-9200) will now cost $130 through Jan 15, 2012.  The slides are packaged in a no contact, non-leaching mBOX® within a vacuum sealed foil bag, so you can confidently order extra quantities at this special price and store them until needed.

Since the first report of fluorous immobilization on glass slides by Prof. Nicola Pohl in 2005, increasing numbers of research groups have been utilizing fluorous surfaces for the immobilization of fluorous tagged materials.  Shortly after the initial report, Fluorous Technologies began offering the slides as a commercial product.  Peptides, carbohydrates, and small molecules have all been immobilized in arrays on these slides and both binding and functional assays have been conducted on fluorous immobilized microarrays.

About Fluorous Technologies Inc.

Fluorous Technologies is a chemical technology company devoted to the development and commercialization of fluorous products for the life science market. The company uses its patented technology to solve synthesis and separation problems spanning the entire drug discovery and development process. Fluorous chemistry enhances a wide range of applications, including medicinal chemistry, combinatorial chemistry, catalysis, biomolecule production, and proteomics.

For more information, please visit: http://www.fluorous.com/

To subscribe to the Fluorous Technical Newsletter, please follow the instructions in our newsletter archive. Unsubscribe information is provided below.

For questions, quotes, orders, product availability, and access to technical resources, please email us or call 412-826-3050.

Fluorous Technologies Inc. is located at 970 William Pitt Way, Pittsburgh, PA 15238 USA.

FluoroFlash® is a registered trademark of Fluorous Technologies Inc.

The International Symposium on Fluorous Technologies 2011 (ISoFT’11) will be held from Nov. 30-Dec 2 at the City University of Hong Kong this year.  ISoFT is a biannual event and is the world’s only conference dedicated solely to the latest in fluorous chemistry and biology.  Prior symposiums have been held in Bourdeaux, Yokohama, and Jackson Hole and were highly informative and fun, providing a great way to meet and interact with the leading scientists in the area.  You can read our coverage of prior ISoFT events in our Newsletter archive as well as on F-Blog (ISoFT’07, ISoFT’09).  We also have a selection of posters and presentations from ISoFT’09 available on our website.

This year’s meeting should be just as good as its predecessors with talks ranging from catalysis to materials to biological probes.  The ISoFT’11 technical program is now available online, and we have highlighted some of the talks and posters below.  ISoFT’11 will surely be as enjoyable as it is stimulating and we at FTI will be able to provide all the materials and expertise you’ll need to conduct your fluorous research once you return home.  In support of the fluorous community, we are pleased to offer all ISoFT’11 attendees a discount on your next purchase.  Please contact us for details.

Lastly, congratulations to  Professor Gianluca Pozzi on his receiving the Fluorous Technologies Award.  He was among the very first fluorous scientists whose work we highlighted in our second ever newsletter, published in August 2002.   At the time Prof. Pozzi had already been working in the field for several years and his wide-ranging career with fluorous techniques and materials continues to this today.

Cheers,

Philip E. Yeske
President & CEO
Fluorous Technologies Inc.

Professor Gianluca Pozzi to Receive Fluorous Technologies Award

One of the highlights of each ISoFT is the Fluorous Technologies Award which this year is being presented to Prof. Gianluca Pozzi of the CNR-Instituto di Scienze e Technologie Molecolari in Milan, Italy.  Prof. Pozzi has made contributions in fluorous asymmetric catalysis, phase transfer catalysis (PTC), and TEMPO oxidations.  He was one of the first to see the potential of fluorous biphasic catalysis with his first paper in the area being published in 1996 and he continues to be actively involved in fluorous catalysis.

His award presentation will be a new area of research in solar cell applications of fluorous dyes. A research area with historic roots in Italy given Giacomo Ciamician’s work in photochemistry and solar energy at the University of Bologna.  Pictured below is a famous photo of Ciamician with flasks and reactions basking in the Italian sun on the rooftop of his laboratories.

Fluorous Methods in Catalysis

Biphasic catalysis was the original embodiment of fluorous separations and remains an active area of research to this day.  Last month’s FTI Technical Newsletter covered  some of the recent developments in fluorous organocatalysts and several talks at ISoFT’11 will be on that topic.  Two presentations at ISoFT’11, however, will be centered on transition metal catalysis using fluorous ligands.  One will be from Prof. Eric Hope  on fluorous palladium catalysis and the other on fluorous Hoveyda-Grubbs catalysts from Prof. Jaroslav Kvicala from the Institute of Chemical Technology in the Czech Republic.

Prof. Hope and Prof. Alison Stuart, both at the University of Leichester, have been working on fluorous palladium and nickel catalysts from some time and have published extensively on the subject.  Earlier this year Prof. Stuart published a communication describing Heck reactions using just such catalysts, so it will be interesting to get an update on the latest from their labs at ISoFT’11.

Last year the Masato group reported the synthesis and reactivity of a fluorous Hoveyda-Grubbs catalyst which could be recovered using fluorous solid phase extraction (FSPE).  It will be intriguing to compare Prof. Kvicala’s results and to see the fluorous separation methods utilized.

Fluorous Methods in Small Molecule Library Synthesis

One of the best applications to date of fluorous methods is in the synthesis of small molecules and small molecule libraries by taking advantage of the orthogonality of the separation, primarily FSPE.  Several presentations on the program will describe the use of fluorous methods in small molecule synthesis including one from Prof. Santos Fustero from the Universidad de Valencia.  They have over the years prepared libraries of compounds using fluorous tags.  In addition, they have done direct comparisons of fluorous methods vs. solid phase methods in library production and found the fluorous phase approach to be superior.  The presentation at ISoFT’11 will describe the synthesis and application of new fluorous tags to library synthesis and purification.

 

Another interesting presentation will be from Prof. Veronique Gouverneur from Oxford University who will be describing her group’s work in fluorous methods in 18-F radiolabelling.  This work earned an Angewandte cover story in 2009 and since that time other groups have utilized fluorous methods in isotope chemistry.   The growth of diagnostic radioimaging has fueled the use of a wider range of imaging agents each of which requires a fast and economical method for preparation.  An update on the progress being made within Prof. Gouverneur’s group should be fascinating.

Fluorous Techniques in Life Sciences

While fluorous catalysis and small molecule synthesis represent some more established applications of fluorous technologies, fluorous techniques in life science applications represents a new wave.  This includes fluorous applications in proteomics, metabolomics, and microarrays.  ISoFT’11 will also touch on these subjects through two presentations.  The first is from Prof. Kenji Monde from Hokkaido University who will describe the synthesis and metabolic analysis of fluorous sphingolipids.  The second is from Man-Wai Louie at City University of Hong Kong who will present their recently published work on fluorous rhenium complexes as biological probes.  Both of these presentations highlight how fluorous methods can not only be used the isolation of tagged compounds from synthetic mixtures, but also enrichment of fluorous derivatized compounds from biological mixtures resulting in increased sensitivity and ease of analysis.  In addition the non-fragmentary and non-signal suppressive MS characteristics of the tags make fluorous methods highly complementary to modern analytical methods.

About Fluorous Technologies Inc.

Fluorous Technologies is a chemical technology company devoted to the development and commercialization of fluorous products for the life science market. The company uses its patented technology to solve synthesis and separation problems spanning the entire drug discovery and development process. Fluorous chemistry enhances a wide range of applications, including medicinal chemistry, combinatorial chemistry, catalysis, biomolecule production, and proteomics.

For more information, please visit: http://www.fluorous.com/

To subscribe to the Fluorous Technical Newsletter, please follow the instructions in our newsletter archive. Unsubscribe information is provided below.

For questions, quotes, orders, product availability, and access to technical resources, please email us or call 412-826-3050.

Fluorous Technologies Inc. is located at 970 William Pitt Way, Pittsburgh, PA 15238 USA.

FluoroFlash® is a registered trademark of Fluorous Technologies Inc.

Over the last decade or so, organocatalysis has been one of the hottest areas of research within the synthetic organic chemistry community.  Interestingly, the use of non-metallic catalysts goes back over 150 years with examples such as von Liebig’s synthesis of oxamide from dicyan using acetaldehyde as a catalyst. Other well-known and oft-employed examples include DABCO for Bayliss-Hillman-Morita reactions and DMAP for acylations.  The current wave of interest in organocatalysis, however, is centered around asymmetric catalysis. Even that development is older than most of us recognize as exemplified by Hajos-Parrish reaction using proline for asymmetric aldol condensations that was first reported in the 1970′s.

In the new millennium, there has been a rapid increase in the pace of research in organocatalysis with the development of many highly stereoselective agents catalyzing a variety of reactions.  In general the major advantages of organocatalysts are their low toxicity and operational simplicity.  The major drawbacks are high loading, often as high as 20 mol%, and difficult recovery.   Since many organocatalysts are costly, recovery and reuse are important factors and have led to the development of numerous phase tagged versions, including fluorous tagged.

Fluorous organocatalysts offer the same set of significant advantages to organocatalysis that it provides for other chemistries: complete solution phase kinetics, ease of monitoring with standard analytical techniques, chemical inertness of the phase tag, and multiple separation modes providing flexibility.  It’s not surprising then that several research groups have developed fluorous organocatatlysts with tremendous commercial potential.  This Newsletter highlights recent developments in fluorous organocatalysts as used in various reaction types- I hope you enjoy getting caught up in this important area.

Cheers,

Philip E. Yeske
President & CEO
Fluorous Technologies Inc.

Aldol Condensations

The aldol condensation is one of the most useful of reactions for C-C bond formation and several fluorous organocatlysts have been developed for this transformation.  A fluorous triazole organocatalyst was reported by Cai and co-workers from Nanjing University which provided the unsaturated aldol product in high yield.  The fluorous triazole was recovered by fluorous solid phase extraction (FSPE).

The Miura group at Gifu Pharmaceitical University has also used FSPE for the recovery and reuse of a fluorous organocatalyst for aldol condensations.  In this instance the beta-hydroxy carbonyl product is isolated in diastreomeric and enantiomeric excess comparable to the non-fluorous version.  The reaction and separation are notable in that the reaction is run in water and can be directly applied to the FSPE cartridge to effect separation and recovery of the organocatalyst.

Earlier in 2008 the Wang group from the University of New Mexico also reported a fluorous sulfonamide based organocatalyst for aldol reactions.  Once again the reaction was run in water and the organocatalyst was recovered by FSPE.  Enantioselectivity was generally good with ee’s around 90% and diastereoselectivity ranged from 5-20:1.

Michael Additions

The Michael addition of nucleophiles to electron deficient olefins is another powerful reaction for the formation of C-C bonds and one that has also been catalyzed by fluorous organocatalysts.  The Miura and Wang groups have once again led the way by employing the same fluorous sulfonamide organocatlysts as in aldol condensations.  The Miura group demonstrated the asymmetric Michael addition of enolizable aldehydes to substituted maleimides as seen below.

Wang et al used their fluorous organocatalyst for the asymmetric Micheal addition of ketones to nitroolefins.  In the latter case, excellent yields, ee’s, and de’s were achieved using 10 mol% loading.  The fluorous sulfonamide was then recovered using FSPE.

Reductive Amination

The formation of secondary amines by reductive amination of aldehydes and ketones is one of the most prevalent reactions in synthetic organic and medicinal chemistry.  This important transformation has been mediated by organocatalysts including fluorous versions.  In 2008, Cai et al from Nanjing University described using a fluorous thiourea to catalyze the reductive amination of aldehydes using a Hantzch 1,4-dipyridine as the stoichiometric reductant.  The fluorous organocatalyst was then readily recovered by FSPE and reused up to 3 times.

Asymmetric reduction of imines using a fluorous organocatalyst has also been described by Kocovsky and co-workers at the University of Glasgow.  In this case  trichlorosilane was used as the reductant and a fluorous tagged N-methylvaline formamide was the catalyst.  Loading levels were from 5-10 mol% and the fluorous organocatalyst was separated from the amine products by FSPE and recycled.  A variety of imines were tested as substrates with ee’s generally in the 85-95% range and catalyst recovery of ~90%.

More Reactions

Fluorous organocatalysts have also been reported in the peer-reviewed literature for reactions other than the ones above.  One is the asymmetric alpha chlorination of aldehydes using a proline derived fluorous thiourea as the organocatalyst.  With N-chlorosuccinimide as the electrophilic chlorine source, alpha-chloro-aldehydes were obtained in good yield and ee.  The organocatalyst was recovered and reused by FSPE.

Cai and co-workers used the fluorous thiourea previously described to catalyze the oxidation of sulfides to sulfoxides with hydrogen peroxide as the oxidant without observing over-oxidation to the sulfone.  Once again FSPE was used to recover the organocatalyst which was reused up to five times.  While the authors have not reported it yet, a chiral version of this organocatalyst would be very interesting.

Get Started with Fluorous Organocatalysts

The expanding range and use of organocatalyts will undoubtedly lead to applications where the separation and recovery of these catalysts will be critical.  As shown, fluorous methods are an excellent option for organocatalyst tagging.  Fluorous Technologies Inc. can help you implement the power of fluorous separations in your research by providing reagents, tags, separation media, and expertise.  Please contact us and we’d be happy to help.

About Fluorous Technologies Inc.

Fluorous Technologies is a chemical technology company devoted to the development and commercialization of fluorous products for the life science market. The company uses its patented technology to solve synthesis and separation problems spanning the entire drug discovery and development process. Fluorous chemistry enhances a wide range of applications, including medicinal chemistry, combinatorial chemistry, catalysis, biomolecule production, and proteomics.

For more information, please visit: http://fluorous.com

To subscribe to the Fluorous Technical Newsletter, please follow the instructions in our newsletter archive. Unsubscribe information is provided below.

For questions, quotes, orders, product availability, and access to technical resources, please email us or call 412-826-3050.

Fluorous Technologies Inc. is located at 970 William Pitt Way, Pittsburgh, PA 15238 USA.

FluoroFlash® is a registered trademark of Fluorous Technologies Inc.

The 242nd American Chemical Society National Meeting and Exposition will be taking place in Denver, CO from Aug. 28-Sept. 11, 2011.  The ACS boasts of being the world’s largest scientific society and fall ACS National Meetings generally have about 15,000 total participants.  With thousands of oral presentations and posters it could be difficult to find items of interest.  The ACS online Technical Program does contain a search function which helps.  For the upcoming meeting there were 48 presentations or posters which contained either “fluorous” or “perfluoro” in the title or abstract (lists of these abstracts can be found on F-Blog).  In this month’s Technical Newsletter we’re highlighting a few of the more interesting titles covering items such as small molecule synthesis, carbohydrate synthesis, and materials chemistry.

Of course, this doesn’t capture all of the presentations using fluorous chemistry since many titles and abstracts may not contain the word fluorous, yet fluorous methods are critical to the success of the project. If your presentation at the Fall ACS National Meeting falls into this category, please contact us and we will be happy to add your presentation or poster to the list.

Cheers,

Philip E. Yeske
President & CEO
Fluorous Technologies Inc.

Small Molecule Synthesis

Several presentations describing either the perfluoroalkylation of small molecules or the use of fluorous tags in synthesis are scheduled.  One of the more interesting titles comes from the Procter lab at the University of Manchester.  The presentation describes their work using fluorous thiol tags for the synthesis of spirooxindole compounds using a Pummerer reaction. Fluorous solid phase extraction (FSPE) plays a vital role in the purification of intermediates throughout the synthetic pathway.

The use of perfluoroalkyl substitution not only provides a separation handle but also modulates chemical and physical properties of molecules.  One example of this will be described in a poster from Prof. Haoran Sun at South Dakota State University.   The researchers prepared various perfluoroalkylated 1,10-phenanthrolines and measured their proton affinities as a function of fluorous substitution.  They cite the solubility of these compounds in hydrofluoroethers (HFEs) as providing the potential of these compounds to bridge the proton affinity scale to fluorous media.

Carbohydrate Synthesis

Prof. Nicola Pohl’s group at Iowa State University has pioneered the use of fluorous tags in carbohydrate synthesis and immobilization.  Her group has several presentations on the docket in Denver, two of which specifically rely on fluorous techniques.  The first is an oral presentation on progress toward the automated synthesis of keratan sulfate fragments.  The full automation of carbohydrate synthesis, akin to automated peptide and oligonucleotide synthesis, remains an elusive goal due to the complexity of carbohydrate chemistry.  Prof. Pohl’s research has used fluorous tags and FSPE as a integral part of the automation process.

The second presentation is a poster describing hydroxylamino based fluorous tags for oligosaccharide immobilization on fluorous modified glass slides.  The poster compares the use of fluorous tags with differing fluorous content in carbohydrate microarray formation.  The fluorous tags, therefore, provide not only the handle by which to prepare and purify the carbohydrates, but also the handle for display orientation specific, noncovalent binding of the oligosaccharides to a surface.

Materials Chemistry

Fluorous modified compounds are finding increased use in materials and nanotechnology due to their unique physical properties.  The fact that fluorous compounds are both hydrophobic and lipophobic and are prone to aggregate to form a separate phase has led to many different types of interesting materials. Efforts led by Prof. Steven Strauss and Olga Boltalina at Colorado State University have concentrated on synthesizing fluorous modified fullerenes for potential use in solar cells.  They will be presenting a number of posters and presentations at the ACS Meeting.  One of these will be within the Division of Fluorine Chemistry’s “Symposium in Honor of Donald J. Burton: ‘Fluorine Chemistry the Iowa Way’” and will describe their studies on using halofullerenes as precursors to fluorous modified fullerenes.

Also within that symposium is a presentation by Dr. Jelena Janjic of Dusquesne University detailing the use of perfluorocarbon emulsions as drug delivery vehicles.  In the work to be described, perfluorocarbon nanoemulsions are used to formulate a theranostic (therapeutic and diagnostic) nanoreagent.  In this instance, a COX2 inhibitor, Celebrex, is formulated for targeted delivery to solid tumors. The accumulation of the delivery vehicle and the tumor response can then be monitored using 19F MRI.

About Fluorous Technologies Inc.

Fluorous Technologies is a chemical technology company devoted to the development and commercialization of fluorous products for the life science market. The company uses its patented technology to solve synthesis and separation problems spanning the entire drug discovery and development process. Fluorous chemistry enhances a wide range of applications, including medicinal chemistry, combinatorial chemistry, catalysis, biomolecule production, and proteomics.

For more information, please visit: http://fluorous.com

To subscribe to the Fluorous Technical Newsletter, please follow the instructions in our newsletter archive. Unsubscribe information is provided below.

For questions, quotes, orders, product availability, and access to technical resources, please email us or call 412-826-3050.

Fluorous Technologies Inc. is located at 970 William Pitt Way, Pittsburgh, PA 15238 USA.

FluoroFlash® is a registered trademark of Fluorous Technologies Inc.

Oligosaccharide synthesis remains one of the most successful applications of fluorous techniques.

Compared to other important biomolecules such as oligonucleotides and peptides, carbohydrates are much more complex. For starters, the number of possible monomeric units is much larger than 4 or even 20. Then there’s the possibility for multiple attachment points between the monomeric units, the stereochemistry of the new bond formed, and the possibility of the linear and branched structures. All of these factors lead to a level of complexity which has precluded the identification of a scalable platform for easy synthesis.

A number of research groups have utilized fluorous synthesis and separation methods to facilitate the preparation and isolation of oligosaccharides. The strategies engaged have varied from fluorous supported synthesis, fluorous capping, fluorous capture and release, to chemoenzymatic synthesis. The number of different groups that have used fluorous techniques and the breadth of stratagems employed are a true testament to the power of fluorous methods for oligosaccharide synthesis. In today’s newsletter we briefly summarize the latest developments from each of these approaches.

Of course, this isn’t limited to just oligosaccharides, as fluorous methods have been applied to a wide range of molecular classes and synthetic methods. If it works for molecules as complex as oligosaccharides it will probably work for you too.

Cheers,

Philip E. Yeske
President & CEO
Fluorous Technologies Inc.

Fluorous Supported Synthesis

This strategy is the fluorous analog to solid-phase supported synthesis where a starting monosaccharide is fluorous tagged and subsequent saccharide units added to it.  After each coupling the newly formed oligosaccharide is purified by fluorous solid phase extraction (FSPE) or fluorous liquid-liquid extraction (FLLE).  The fluorous supported strategy has several advantages over the solid-phase approach, primarily due to the fact that the chemistry is conducted entirely in solution.  These advantages include faster reaction kinetics, easy analysis and purification of intermediates, and the use of lower amounts of reagents and monomer units.  The last item in particular is important since in many instances the synthesis of the monosaccharides themselves can be daunting.  Fluorous supported oligosaccharide synthesis has been pursued by several groups, most notably Prof. Pohl at Iowa St. University who uses a FSPE as the primary purification method and Prof. Mizuno at the Noguchi Institute who has used FLLE.

Fluorous Capping

Prof. Peter Seeberger has been a pioneer in the development of solid phase synthesis of oligosaccharides. Much like peptide and oligonucleotide solid phase synthesis the iterative reaction sequence is coupling of a protected monomer unit, capping of any uncoupled oligomer, followed by deprotection of the oligomer. The capping minimizes the presence of any deletion sequences that may occur due to inefficient coupling. Upon release from the solid phase, the full-length oligosaccharide needs to be separated from the capped deletion sequences.

One of the strategies used by the Seeberger group is capping with a fluorous reagent. FSPE was then used to separate the non-fluorous desired oligosaccharide from the fluorous capped deletions.  A second solid phase approach used by Seeberger used traditional acetyl capping of the deletion sequences with fluorous tagging of the terminal saccharide unit on the desired oligosaccharide.  In this approach the capped deletions were non-fluorous while the full-length oligosaccharide was fluorous.  In either strategy the desired oligosaccharide was isolated in high purity and with high recoveries.

Fluorous Capture and Release

Prof. Xuefei Huang’s group at Michigan St. University has applied a fluorous capture and release strategy to one-pot oligosaccharide synthesis in order to separate the desired product from a complex mixture of reagents and monosaccharides.  The one-pot synthesis was conducted starting from a monosaccharide with a linker containing a reactive functional group, in this case, a ketone.  After construction of the full oligosaccharide a fluorous hydrazide is then added to the pot resulting in fluorous capture of the oligosaccharide which is then isolated by FSPE.  Release of the full-length product is then achieved by hydrolysis of the hydrazone. The researchers made a variety of linear and branched oligosaccharides including LewisX trisaccharide shown below which was impressively produced in just over 4h and in 62% yield.  The fluorous capture and release strategy is an excellent example of how fluorous methods can be used to augment and improve currently employed methods.

Fluorous Chemoenzymatic Synthesis

One of the hallmarks of carbohydrate chemistry is the extensive use of protecting groups to ensure that coupling of the individual sugar units occurs only at one hydroxyl group. This adds to the length and complexity of the synthesis of both the monosaccharides and the oligosaccharide. One way around this is to employ a chemoenzymatic synthesis which regio-and stereoselectively gylcosylates specific saccharide units.

Prof. Jian Liu at the UNC-Chapel Hill has done just that in his group’s fluorous chemoenzymatic synthesis of heparan sulfates. The placement and use of the fluorous tag was similar to that used by Prof. Pohl in fluorous supported approach.  In the chemoenzymatic approach, however, the reactions were conducted in aqueous solution and the saccharide units were unprotected. In addition to the glycosyltransferases, epimerases, and sulfotransferases were also utilized. The addition of the fluorous tag facilitated isolation of the product after enzymatic glycosylation and increased recovery from 40% to 80%. This and other enzymatic syntheses demonstrate the breadth of chemistries which are compatible with fluorous methods.

More Fluorous Carbohydrate Applications

Fluorous techniques are not limited to only synthesis and purification. Fluorous tagged carbohydrates have also been used in glycomics applications such as carbohydrate microarrays and sample enrichment of carbohydrates in biological samples.

About Fluorous Technologies Inc.

Fluorous Technologies is a chemical technology company devoted to the development and commercialization of fluorous products for the life science market. The company uses its patented technology to solve synthesis and separation problems spanning the entire drug discovery and development process. Fluorous chemistry enhances a wide range of applications, including medicinal chemistry, combinatorial chemistry, catalysis, biomolecule production, and proteomics.

For more information, please visit: http://fluorous.com

To subscribe to the Fluorous Technical Newsletter, please follow the instructions in our newsletter archive. Unsubscribe information is provided below.

For questions, quotes, orders, product availability, and access to technical resources, please email us or call 412-826-3050.

Fluorous Technologies Inc. is located at 970 William Pitt Way, Pittsburgh, PA 15238 USA.

FluoroFlash® is a registered trademark of Fluorous Technologies Inc.

Fluorous Technologies Inc. was founded a decade ago as the world’s first company dedicated to the implementation of fluorous methods for the synthesis and purification of small molecules.  Our primary customers were industrial and academic organic chemistry labs.  As the technology and the company have matured, the application of fluorous methods has spread to other areas such as chemical biology and materials chemistry, but to this day small molecule chemists remain our most frequent and loyal customers. Those chemists which have implemented fluorous techniques come back to it again and again to facilitate purification.  No matter if you’re making small focused libraries or single compounds, mg quantities or kg quantities, fluorous chemistry can help make your life easier.

Cheers,

Philip E. Yeske
President & CEO
Fluorous Technologies Inc.

Small Molecule Synthesis Using Fluorous Tags

The tagging of substrates using fluorous tags is a highly effective strategy for either single compound or library synthesis.  These tags are often fluorous versions of commonly used protecting groups such as BOC, Cbz, or silanes, and maintain reaction profiles similar to their non-fluorous analogs. Heteroatoms can be protected as normal and the tagged substrate carried through multiple reactions before detagging as normal, for example acid deprotection of a F-Boc group. Throughout the synthesis the fluorous tag can be used to easily and quickly purify the intermediates by fluorous solid phase extraction (FSPE).  The generality of FSPE separations allows all intermediates and analogs to be purified using a single method — greatly simplifying the separation and minimizing method development.

A good recent example of fluorous tagging was provided by Sanz-Cervera et al who made a library of thiazoles and azoles.  The authors tagged the compounds by protecting a carboxylic acid as the fluorous ester.  They compared fluorous tagged and non-fluorous synthetic strategies and concluded that the fluorous approach resulted in substantial time savings in the production of the library.  The compounds were then tested for their anti-bacterial activity.

Fluorous Reagents and Scavengers

Another strategy which has proven to be effective is the use of fluorous reagents and scavengers.  In this instance the substrate remains non-fluorous.  Reagent by-products or excess reagents can then be separated from the desired compound by FSPE or fluorous liquid-liquid extraction (FLLE) in some cases. Unlike solid-supported reagents, fluorous reagents and scavengers are soluble in common organic solvents resulting in solution phase kinetics and precise stoichiometric control.

A prime example of fluorous reagents in synthesis is the Mitsunobu reaction using a fluorous phosphine and a fluorous diazodicarboxylate.  Both the phosphine oxide and the reduced diazodicarboxylate by-products can be easily separated from the Mitsunobu product using a fluorous separation. Prof. Nicolas Winssinger and co-workers used a fluorous Mitsunobu reaction as a key macrolactonization step in their synthesis of radicicol A analogs. Fluorous Technologies Inc. provides a range of fluorous reagents and scavengers including fluorous versions of tin hydride for reductions, hypervalent iodonium salts for oxidations, carboxy activating reagents, and nucleophilic and electrophilic scavengers.

Fluorous Mixture Synthesis

Fluorous reagent-based chemistry was not the only fluorous method that the Winssinger Group employed in the radicicol A synthesis.  In order to increase the number of analogs produced without increasing the number of individual reactions, they also used fluorous mixture synthesis (FMS) in the radicicol A library shown above.  Since fluorous HPLC can separate compounds based on the length of the fluorous tag, mixtures of compounds can be simultaneously produced in the same pot.  The individual compounds can then be separated in a predictable order using F-HPLC.  Many of our most popular tags are available in various fluorous chain lengths for use in mixture synthesis applications.

Natural product structure elucidation, primarily in the assignment of remote relative stereochemistry, has also been conducted using FMS.  By working with a mixture of uniquely tagged stereoisomers that can be later separated and unambiguously identified, all possible stereoisomers of a compound can be prepared without having to synthesize each individually.  The synthesis and structure confirmation of petrocortyne A is a recent example of FMS in action.  Petrocortyne A was isolated and structural assignment made by two different groups, each of whom assigned different absolute stereochemistry to the two chiral centers.  In order to unambiguously assign stereochemistry Curran et al synthesized all four possible stereoisomers using FMS and compared spectra of all four with that reported in the literature from both groups to determine the correct stereochemistry.

Fluorous Kits

A good way to see for yourself just how easy and quick fluorous methods can is to order a fluorous trial kit. The trial kit include two FSPE cartridges, a sample of the fluorous dye mixture, 500 mg of a fluorous tag (F-CBz) and a fluorous scavenger (F-Thiol), along with application notes.  This simple kit will allow you try a FSPE with visualization and then try a couple of reactions.

In addition to the trial kit we have also compiled a fluorous tagging module, a fluorous scavenging module, and a fluorous transformation kit.  The tagging and scavenging modules contain FSPE cartridges and 4-5 different compounds in multigram amounts in a display stand and are designed to be readily available for use within a laboratory.  The transformation kit is our most complete kit and includes an array of reagents and scavengers for functional group transformations along with FSPE cartridges and application notes.   Each of these can also be customized to best fit your laboratory and research needs.

If you have any questions about these products or any of the items mentioned please do not hesitate to contact us.

About Fluorous Technologies Inc.

Fluorous Technologies is a chemical technology company devoted to the development and commercialization of fluorous products for the life science market. The company uses its patented technology to solve synthesis and separation problems spanning the entire drug discovery and development process. Fluorous chemistry enhances a wide range of applications, including medicinal chemistry, combinatorial chemistry, catalysis, biomolecule production, and proteomics.

For more information, please visit: http://fluorous.com

To subscribe to the Fluorous Technical Newsletter, please follow the instructions in our newsletter archive. Unsubscribe information is provided below.

For questions, quotes, orders, product availability, and access to technical resources, please email us or call 412-826-3050.

Fluorous Technologies Inc. is located at 970 William Pitt Way, Pittsburgh, PA 15238 USA.

FluoroFlash® is a registered trademark of Fluorous Technologies Inc.

Some twenty years ago the partitioning of fluorous tagged molecules into a fluorous liquid phase for separations was the first embodiment of the technology.  More recently another manifestation of selective fluorous partitioning, the immobilization of fluorous molecules onto a fluorous solid surface, has been an active area of research. These surfaces can be 2-D or 3-D and can be used for analytical or synthetic purposes.  Analytical applications have been primarily in the form of microarray formation using either fluorescence or MS readout, while synthetic applications have been in the recovery and reuse of catalysts. No matter the design, fluorous immobilization is a highly selective, bioorthogonal,  non-covalent immobilization allowing a high degree of flexibility and versatility- and FTI can provide you with all the technical assistance and materials you need to immobilize your molecules and gain all the advantages of fluorous techniques.

Cheers,

Philip E. Yeske
President & CEO
Fluorous Technologies Inc.

Immobilization on Fluorous Glass Slides

The first report of the immobilization of fluorous molecules on fluorous glass slides was by Prof. Nicola Pohl in 2005.  Since that time various groups have used fluorous glass slides in conjunction with fluorescence detection to interrogate carbohydrate-lectin, small molecule-protein, and peptide-enzyme interactions. Fluorescence detection in the form of fluorescently tagged proteins, fluorogenic probes, and sandwich type assays have all been successfully performed on fluorous microarrays.  In addition different spotting strategies have also been demonstrated including on-surface fluorous tagging through click chemistry.  In 2010 researchers at the Broad Institute have also published a detailed protocol for formation of small molecule microarrays making the use of fluorous glass slides even easier.

Fluorous glass slides have several advantages over other modified glass surfaces including low and uniform background fluorescence, low non-selective binding thereby reducing wash and blocking steps, smaller feature diameters, and specific probe display orientation.

Fluorous Microarrays with Direct MS Detection

With non-covalent fluorous microarrays you can use direct MS analysis to provide structural information and detection of many reversible substrate-enzyme interactions that you generally cannot obtain with fluorescence methods.  Here are several examples using this innovative approach.

Prof. Gary Siuzdak and Chi-Huey Wong at The Scripps Research Institute have both effectively used fluorous modified surfaces for the immobilization and MS detection of fluorous tagged peptides and carbohydrates.  Prof. Siuzdak has published two methods: fluorous desorption/ionization on silicon mass spectrometry (DIOS) and nanostructure-initiator MS (NIMS).

Fluorous DIOS

In fluorous DIOS, mixtures containing fluorous peptides were spotted onto  a fluorous modified silicon surface. The microarray was then washed with water to perform an on-surface enrichment. The fluorous peptides were directly ionized from the surface.

Fluorous Nanostructure-Initiator MS (NIMS)

In NIMS, fluorous tagged carbohydrates were immobilized on a surface containing a fluorous silane as a nano-initiator.  The microarrays were then incubated with cell lysates containing hydrolases or glycosylases specific to the substrates.  The products of these enzymatic reactions could then be confirmed by MS analysis, a process which the authors dubbed Nimzyme.

Prof. Wong, who was a co-author on the Nimzyme paper, has separately published a paper using fluorous modified aluminum oxide surfaces for carbohydrate microarray formation with MS detection.  They were in fact able to conduct either fluorescence or MS detection with the microarrays providing excellent flexibility. Once again the low level of non-selective binding to the surface allowed for incubation with cell lysates to investigate substrate transformations in the presence of cellulases.

Each of these methods for direct MS readout from the microarray surface cannot be done using covalent immobilization.  The combination of the non-covalent bonding, high selectivity, specific probe orientation, and non-fragmentary behavior of the tag makes fluorous immobilization the best choice for MS-based detection methods.

Fluorous Reagents and Catalysts Immobilized on Fluorous Surfaces

Microarrays are not the only application of fluorous immobilization on surfaces.  Reagent and catalyst recovery on fluorous modified surfaces has been a mainstay of fluorous chemistry for some time.  These chemistries are very similar to the original fluorous biphasic catalysts concept, but replace the fluorous liquid phase with a solid phase.

Fluorous Silica Gel as Immobilization Surface

One of the first known examples was published by Bannwarth et al in 2002 who immobilized fluorous Pd catalysts on fluorous silica gel in situ, added the fluorous silica gel supported catalysts to a reaction, then used simple filtration to remove the catalyst.  Prof. Bannwarth has continued this work using other fluorous materials as the solid phase.

Teflon Tape immobilizing Fluorous Catalysts

Perhaps the best example of fluorous immobilization of catalysts on a surface, however, is the work Prof. John Gladysz usingTeflon® tape and Gore-Rastex® fiber as the fluorous surface.  The large surface area to volume ratio of the tape or fiber results in better recovery of the catalyst.  Once again, simple removal of the solid phase removes the catalyst from the reaction.  Prof. Gladysz also envisions tape or fiber with catalyst immobilized on it so adding catalyst to a reaction would be nothing more than cutting off an appropriate length of tape.  These examples and others illustrate how the partitioning of fluorous tagged molecules onto a fluorous solid phase can be used to effect homogeneous catalysis with heterogenous-like catalyst removal.

About Fluorous Technologies Inc.

Fluorous Technologies is a chemical technology company devoted to the development and commercialization of fluorous products for the life science market. The company uses its patented technology to solve synthesis and separation problems spanning the entire drug discovery and development process. Fluorous chemistry enhances a wide range of applications, including medicinal chemistry, combinatorial chemistry, catalysis, biomolecule production, and proteomics.

For more information, please visit: http://fluorous.com

To subscribe to the Fluorous Technical Newsletter, please follow the instructions in our newsletter archive. Unsubscribe information is provided below.

For questions, quotes, orders, product availability, and access to technical resources, please email us or call 412-826-3050.

Fluorous Technologies Inc. is located at 970 William Pitt Way, Pittsburgh, PA 15238 USA.

FluoroFlash® is a registered trademark of Fluorous Technologies Inc.

As every practicing scientist knows, one of the best ways to see and be seen is at conferences and meetings.   Listening to an oral presentation or viewing a poster and being able to engage and ask questions with the researcher is a great way to learn more about the subtleties, complexities, and importance of a given piece of research.  Given the breadth of applications that have evolved based on fluorous techniques it’s a good bet that many conferences have at least one person presenting work containing a fluorous separation.   Sometimes these talks aren’t so easy to find since the title or abstract may not contain the word “fluorous”, but we seek them out.   As a service to conference attendees,  we’ll highlight some of the more interesting presentations as technical programs become available.  Several notable talks and papers are listed below.  For those of you presenting work that contains fluorous methods, please contact us and we’ll make sure to get the word out.

Cheers,

Philip E. Yeske
President & CEO
Fluorous Technologies Inc.

Spring 2011 American Chemical Society National Meeting

The semi-annual ACS Meeting is one of the biggest meetings in the world for chemists.  This year’s spring meeting will be held March 27-31 in Anaheim, CA.  A search of the online technical program found over 30 presentations using perfluorocarbons.  The topics range from synthesis of fluorous materials to biphasic catalysis to surface chemistry.  Some of the more interesting scheduled presentations from a fluorous perspective include the following:

Title:  Catalyst recovery protocols based upon fluoropolymers
Authors: Markus Jurisch, John Gladysz
Date/Time: Wednesday, March 30 – 4:00 PM
Location: Anaheim Convention Center, 207 A/B

Title:  Synthesis and characterization of a novel recyclable Pd N-heterocyclic carbene catalyst
Authors: Libbie S.W. Pelter, Kraig R. Kmiotek
Date/Time: Monday, March 28 – 4:35 PM
Location: Anaheim Convention Center, 203 A/B

Title: α,ω – Diperfluorohexyl substituted oligothiophenes as n-type semiconductors for OFETs: Synthesis and structure property relationships
Authors: Hayden T. Black, Valerie S. Ashby
Date/Time: Tuesday, March 29 – 11:00 AM
Location: Anaheim Convention Center, 204c

Title: Effects of surface chemistry on ionic liquid droplet formation in a microfluidic device for reaction synthesis
Authors: Carson Riche, Noah Malmstadt, Malancha Gupta
Date/ Time: Monday, March 28 – 6:00 PM
Location:  Disneyland Hotel, South Exhibit Hall

59th American Society for Mass Spectrometry Conference

ASMS is the premier annual conference for mass spectrometry and allied topics.  The 59th edition of ASMS will be held in Denver from June 5-9, 2011.  Mass spectrometry has become the method of choice for the analysis and identification of compounds in proteomics, metabolomics, and analytical chemistry.  Sample enrichment often plays a key role in order to reduce sample complexity and to enhance sensitivity.  The selectivity, ease, and non- MS fragmentary behavior of fluorous tags makes enrichment strategies based on fluorous separations an attractive alternative to biotin-avidin based enrichment.

2010 saw a marked increase in the number of papers using fluorous enrichment methods, so we anticipate that the 2011 ASMS conference should also see a number of presentations using fluorous methods in proteomics and metabolomics.  In addition it will not be surprising to see the use of fluorous modified MS surfaces such as nanostructure-initiator MS (NIMS) or aluminum oxide surfaces at ASMS.  Once the technical program becomes available we’ll be sure to make you aware of those presentations.

Gordon Research Conference on Carbohydrates

If smaller,  focused conferences are more to your liking, then nothing tops a Gordon Research Conference.  The GRC Carbohydrates meeting slated for mid-June at Colby College in Maine is sure to have some talks about fluorous chemistry.  Carbohydrates have become one of the best applications of fluorous methods.  The co-chair of the conference is Prof. Nicola Pohl, a pioneer in fluorous supported carbohydrate synthesis and fluorous micorarrays.  In addition, one of her former students, Dr. Beatrice Collett is scheduled as a speaker.

The small, informal nature of Gordon Conferences which are usually set in small colleges away from big urban centers presents a unique venue which encourages discourse amongst participants.  If you’re a researcher in this area and want to know more about fluorous methods in carbohydrates this would be an excellent meeting to attend.  The deadline to submit your application to attend GRC Carbohydrates is May 22.

International Symposium on Fluorous Technologies 2011

Near the end of the year is the biggest fluorous conference of them all, ISoFT’11, the biannual meeting dedicated exclusively to fluorous chemistry.  This year’s meeting will be held Nov. 30-Dec. 2 at City University of Hong Kong.  A preliminary list of scientific themes and plenary and invited speakers is available on the ISoFT’11 website.  Nearly all the world’s leading researchers in fluorous chemistry are sure to be participating providing an unique opportunity for all those that are interested in applying fluorous methods to their work.  Throughout the year we will keep you informed about important upcoming dates and developments.

Expand the Reach of Your Fluorous Research

If you are presenting research involving fluorous techniques, please let us know.  We’ll be glad to highlight it in future newsletters and blog posts, as well as host a an electronic copy on our presentations page.

About Fluorous Technologies Inc.

Fluorous Technologies is a chemical technology company devoted to the development and commercialization of fluorous products for the life science market. The company uses its patented technology to solve synthesis and separation problems spanning the entire drug discovery and development process. Fluorous chemistry enhances a wide range of applications, including medicinal chemistry, combinatorial chemistry, catalysis, biomolecule production, and proteomics.

For more information, please visit: http://fluorous.com

To subscribe to the Fluorous Technical Newsletter, please follow the instructions in our newsletter archive. Unsubscribe information is provided below.

For questions, quotes, orders, product availability, and access to technical resources, please email us or call 412-826-3050.

Fluorous Technologies Inc. is located at 970 William Pitt Way, Pittsburgh, PA 15238 USA.

FluoroFlash® is a registered trademark of Fluorous Technologies Inc.

This Newsletter attempts to look ahead and predict what 2011 holds for fluorous technology.  As Niels Bohr once said however, “Predictions are very difficult, especially about the future.”

Of course that’s one of the strengths of fluorous techniques: predictability.  Not in new applications or capabilities, which have continually surprised even us, but in predictable separation outcomes. Due to the near-orthogonality and high selectivity of fluorous based separations their outcomes are generally highly predictable.  This predictability — used to great effect in established fields like small molecule synthesis, biomolecule synthesis and purification, and life science applications — supports the up-and-coming areas that we highlight below.

We invite you to help shape the fluorous news in the upcoming year.  Contact us with your questions and product needs and we’ll help you incorporate fluorous technology in your research.  Stay connected through our newsletters and blog posts.  Join us at ISoFT’11 as we celebrate and honor your cutting edge fluorous work.   Together, let’s make 2011 the best and most productive year possible.

Cheers,

Philip E. Yeske
President & CEO
Fluorous Technologies Inc.

Fluorous Glycomics

Synthesis, purification, and enrichment of carbohydrates are several of the most exciting fluorous applications.  The next step is to use fluorous methods in glycomics, the comprehensive study of all carbohydrates in living systems whether free or as complexes.  Glycosylation, for example, is one the most common and important posttranslational modifications.  Fluorous methods can be used for the enrichment of post-digestion glycosylated peptides to identify glycosylated proteins.  Identification of the glycan and the site of glycosylation are often conducted using MSⁿ techniques for which fluorous tags are well-suited.  Fluorous-based carbohydrate microarrays for the study of carbohydrate-protein interactions are another fluorous glycomics tool that is ready for expanded use in 2011.

Fluorous Organocatalysts

Fluorous organocatalysts ease separation, recovery, and reuse of these interesting catalysts through either fluorous solid phase extraction (FSPE) or fluorous liquid-liquid extraction (FLLE).  Proper design and placement of the fluorous tag results in an organocatalyst that is very similar to the original non-fluorous version in terms of reactivity and selectivity.  Their appeal is the fact that no toxic metals are used resulting in no metal residues to remove from the product.  Transformations which have been reported to date include asymmetric aldol reactions,  Michael additions, stereoselective alpha-chlorinations, and reductive aminations.  In 2011 we anticipate that continued development of new fluorous organocatalysts and advances in fluorous reaction & separation processes will lead this catalytic technology off the bench and into the plant.

Fluorous Nanotechnology

Nanotechnology is a very active field, and it’s no surprise that fluorous techniques easily adapt to the nano realm.  Fluorous nanoparticles have very interesting properties depending on whether the fluorous domain is interior or exterior to the particle.   Those with interior fluorous domains create a fluorous environment that encapsulates fluorous materials.  Nanoparticles with exterior fluorous domains self-aggregate in a fluorophobic environment or absorb onto fluorous modified materials.  The preparation and purification of these nanoparticles is facilitated by the use of fluorous separation methods.  Fluorous nanoparticles have already been used in a variety of applications including DNA detection,  homogeneous catalysis, and PET imaging.    It will be interesting to see over the next year what other applications await fluorous nanoparticles.

International Symposium on Fluorous Technologies 2011 (ISoFT’11)

The fourth edition of ISoFT will be held this year from Nov 30-Dec 2 at the City University of Hong Kong and will cover a range of fluorous applications from basic research to computational chemistry to biological applications.  The ISoFT’11 website is now live and includes valuable items such as a list of plenary and invited speakers, abstract submission and registration deadlines, and other conference related information.  If you have used fluorous methods in your research we encourage you to share your results through a poster or oral presentation.  If you plan on using fluorous methods and would like to learn more than this is the conference to attend allowing you access to leaders in the field.

About Fluorous Technologies Inc.

Fluorous Technologies is a chemical technology company devoted to the development and commercialization of fluorous products for the life science market. The company uses its patented technology to solve synthesis and separation problems spanning the entire drug discovery and development process. Fluorous chemistry enhances a wide range of applications, including medicinal chemistry, combinatorial chemistry, catalysis, biomolecule production, and proteomics.

For more information, please visit: http://fluorous.com

To subscribe to the Fluorous Technical Newsletter, please follow the instructions in our newsletter archive. Unsubscribe information is provided below.

For questions, quotes, orders, product availability, and access to technical resources, please email us or call 412-826-3050.

Fluorous Technologies Inc. is located at 970 William Pitt Way, Pittsburgh, PA 15238 USA.

FluoroFlash® is a registered trademark of Fluorous Technologies Inc.

2010 was another exciting year in the use of fluorous techniques for synthesis, separation, and enrichment applications.  Fluorous methods have been proven to be effective in the separation of targeted compounds from complex mixtures.  Sometimes these molecules may consist of a single compound, such as in the synthetic preparations, and other times they may consist of a class of molecules as in proteomic or metabolomic applications.  2010 saw many peer-reviewed reports of both single compound and compound class separations with fluorous methods.  Highlighted below are what we view as some of the more important developments in fluorous chemistry in 2010.

Cheers,

Philip E. Yeske
President & CEO
Fluorous Technologies Inc.

Bioanalytical and Analytical Applications

The enrichment of specific molecular subsets from complex mixtures is part of the basis of fluorous life science applications.  In protoemics and metabolomics, sample preparation which simplifies these mixtures to exclude those molecules which are not of interest and to include only those that are of interest is critical to detection and quantitation.  The novel separation modality and the demonstrated sensitivity of fluorous based enrichment methods when combined with modern MS techniques has led to some interesting new protocols for sample prep and enrichment.

Fluorous Tags and FSPE Enrich Targeted Metabolite Classes

Two separate research groups enriched various fluids and tissues for two important classes of metabolites, glycosphingolipids and sialic acids, using fluorous tagging.  The biological sample was either pre-fractionated into a sample containing the molecules of interest or used directly depending on the sample.  The analytes of interest were selectively fluorous tagged and the sample enriched for those analytes by fluorous solid phase extraction (FSPE).  Pictured below is the enrichment of three sialic acids from human urine as reported by Hayama et al.  One of the most important features is the non-fragmentary nature of the fluorous tag which does not complicate interpretation of the MS-MS spectra.

Orthogonal Separation Enables Analysis in Complex Samples

In addition to FSPE, fluorous liquid-liquid extraction (FLLE) was effectively utilized in 2010 for the analysis of perfluorocarbon (PFC) pollutants from hydrophobic matrices.  Fluorous methods are especially useful in these instances due to the orthogonality of the separation to polarity-based methods.  In addition, solvent tuning allows one to balance the selectivity with the overall recovery to achieve the desired level of each.  This was demonstrated in 2010 by scientists at the University of York who were able to detect PFC pollutants in fatty matrices such as cheese to the 1 ppb level.

Carbohydrate Synthesis

Biomolecule synthesis using fluorous tags remains one of the best applications of fluorous methods, particularly oligosaccharide preparation where automated methods are not generally accessible.  The difficulty of oligosaccharide synthesis, which often leads to complex synthetic mixtures requiring tedious chromatographic separations, makes it an ideal candidate for a fluorous solution.  2010 saw several great examples of the application of fluorous methods in these often challenging preparations.

Fluorous Tags for Chemoenzymatic Synthesis

Prof. Jian Liu at the University of North Carolina used a fluorous tag in the chemoenzymatic synthesis of heparan sulfates.  The octasaccharide backbones were synthesized using a fluorous benzylamine tag that provided both a handle for fluorous solid phase extraction (FSPE) and  a UV chromaphore to assist in reaction monitoring by HPLC.  The authors used a series of bacterial enzymes including glycosyl-transferases, an epimerase, and a sulfo-transferases to produce the final products.  Beyond demonstrating the compatibility of fluorous tags with enzymatic methods, in the reaction mediated with Kfia, a glucosyl transferase, they recovered 80% of the product of reaction when fluorous was employed vs. only 40% without the aid of the fluorous tag.  Since the glycosyl transferase reaction was used in an iterative fashion, this resulted in a tremendous increase in efficiency over the entire synthesis.  This work not only demonstrated the power of the fluorous purification, but also it’s compatibility with enzymatic reactions.

Fluorous Catch and Release Strategy for One-pot Synthesis

Fluorous supported chemistry as exemplified in the work above is not the only method by which fluorous tags were used in 2010.  Prof. Xufei Huang at Michigan State University reported the use of fluorous catch and release methods in one-pot oligosaccharide synthesis.  In this approach carbohydrates are reacted in a single pot and the order of addition along with reactivity profiles of the monomeric units lead to the correct assembly of the desired oligosaccharide.  Purification is then facilitated by capture of the desired sequence with a fluorous tag that reacts preferentially with an appropriately paired reactive group on the reducing end of the sugar.  Fluorous solid phase extraction is used to separate this product from excess reagents, monomers, and undesired products.  The full oligosaccharide is then released from the fluorous tag.  The authors were able to very quickly synthesize a number of linear and branched oligosaccharides using this strategy.

These are just two examples of how fluorous methods can help in the isolation of compounds from synthetic mixtures.  Oligonucleotides and peptides can also be purified using similar strategies.

Fluorous Small Molecule Synthesis

While the most mature of the three major applications of fluorous methods, fluorous small molecule synthesis is by no means stagnant.  New methods, reagents, and tags are continually being introduced by the worldwide research community.

Standard Purification Methods for Diversity Oriented Synthesis

Prof. Adam Nelson from the University of Leeds continued his work using fluorous tags and olefin metathesis for the construction of libraries with unparalleled molecular diversity.  This year he introduced the combination of using olefin metathesis and Diels-Alder chemistry to quickly access a variety of molecular scaffolds as pictured below.  The fluorous tag and FSPE facilitated purification at each stage of the synthesis, while the “catch and release” element of the reaction design only allowed the products of successful metathesis reactions to be released from the fluorous tag.  Upon FSPE the successful olefin metathesis products were easily separated from unreacted starting materials or other by-products.

Fluorous Synthons in Parallel Synthesis

In the area of fluorous synthons, Kristensen and co-workers at the University of Copenhagen developed a fluorous alkoxyamine as an ammonia equivalent.  The fluorous alkoxyamine could be used in a number of different reactions for the formation of primary and secondary amines and amides.  The intermediates could be purified with either fluorous liquid-liquid extraction or FSPE.  As a demonstration of its utility the researchers synthesized the anti-dyspepsic drug itopride in high purity(>49%) without any chromatography.  The authors concluded that a parallel synthesis of a library of itopride analogs using this new synthon would be ideal.

Catch up on all the Fluorous News from 2010

Stay Current with Up to Date Reports on F-Blog

Our primary channel for presenting the latest from the scientific literature in fluorous chemistry and biology is F-Blog.  By the end of 2010 we will have published over 80 separate posts covering items of interest from the past year.  Each post is categorized by topic and easily viewable by keyword from the main page.  RSS feeds are available for those who would like to subscribe using the reader of your choice.

Dive Deeper into Key Topics with Fluorous Technical Newsletters

This past year we issued seven Fluorous Technical Newsletters that detailed the state of the art in the chosen area.  In case you missed any or would like to review, here they are:

• Fluorous Separation Techniques
• Fluorous Techniques Complement and Enhance other Technologies
• FluoroFlash® Silica Gel for Fluorous Separations
• Fluorous Chemistry Recognized at the 2010 Fall ACS Meeting
• Isotope Chemistry using Fluorous Techniques
• Fluorous Metabolomics
• Fluorous Oligonucleotide Synthesis and Purification

Looking Forward to 2011

Since its inception Fluorous Technologies Inc. has been dedicated to the advancement and implementation of this novel separation and enrichment method. Our mission has been to help researchers around the world accomplish their goals through the use of fluorous techniques.  We’d like to help you get started with fluorous techniques in the coming year.

If upon learning about the capabilities and applications of fluorous methods you have questions regarding implementation to your research, please contact us directly.  We would be more than happy to provide you with all the information and tools needed to reach your goals in 2011.

About Fluorous Technologies Inc.

Fluorous Technologies is a chemical technology company devoted to the development and commercialization of fluorous products for the life science market. The company uses its patented technology to solve synthesis and separation problems spanning the entire drug discovery and development process. Fluorous chemistry enhances a wide range of applications, including medicinal chemistry, combinatorial chemistry, catalysis, biomolecule production, and proteomics.

For more information, please visit: http://fluorous.com

To subscribe to the Fluorous Technical Newsletter, please follow the instructions in our newsletter archive. Unsubscribe information is provided below.

For questions, quotes, orders, product availability, and access to technical resources, please email us or call 412-826-3050.

Fluorous Technologies Inc. is located at 970 William Pitt Way, Pittsburgh, PA 15238 USA.

FluoroFlash® is a registered trademark of Fluorous Technologies Inc.