August 2002 Technical Newsletter
August 2002 Fluorous Technical Newsletter
Fluorous Technologies Inc.
Fluorous Technologies, Inc. (FTI) is a chemical technology company dedicated to the development and commercialization of fluorous products focused at the life science market. The company employs patented technology to solve unmet synthesis and separation problems across the entire drug development process. FTI further leverages its enabling technology through service contracts, licenses, and collaborations.
Solution Phase Scavengers Take Hold
A June 2002 article in Modern Drug Discovery Magazine entitled ” Fluorous solution phase scavengers capture excess reagents and a simple solid phase extraction over FluoroFlash® silica gel removes both the scavenged products and any excess scavenger. Compared to related solid phase scavenging reactions, the fluorous reactions are faster, cleaner, and do not require large excesses of scavenging reagents.
Innovative fluorous scavenging methods are introduced in a recent publication in Tetrahedron Letters by medicinal chemists Lindsley, Zhao, and Leister of Merck Research Laboratories entitled “Fluorous-Tethered Quenching Reagents for Solution Phase Parallel Synthesis” To fuel this area of research, FTI has recently expanded its product offering to include the following Nucleophilic (F-Thiol, F-Propylamine, and F-Benzylamine) and Electrophilic (F-Ethyl Isocyanate, F-Oxybenzaldehyde, and F-Isatoic Anhydride) scavengers.
In recent published work entitled “Use of fluorous silica gel to separate thiol quenching derivatives in solution-phase parallel synthesis,” researchers at FTI used commercially available href=”http://fluorous.com/nscavengers.html”>fluorous thiols (RfCH2CH2SH) combined with FluoroFlash® silica gel SPE to remove excess electrophiles in the parallel synthesis of a tertiary amine library. Fluorous quenching conducted in a homogenous medium had favorable reaction kinetics and in a side by side comparison required less amount of scavenging reagent as compared to solid-bound scavengers. In addition, the quenching reaction using a fluorous thiol was found to be 5-10 times faster than that of a polymer-supported thiol. To learn more about this application, contact Dr. Wei Zhang.
Enantiomer Synthesis – Racemic, Asymmetric, or Fluorous Quasiracemic?
Like asymmetric synthesis, fluorous quasiracemic synthesis starts and finishes with enantiopure compounds, but like racemic synthesis, it provides both enantiomers in a single synthesis. In a paper entitled “Quasiracemic Synthesis: Concept and Implementation with a Fluorous Tagging Strategy to make Both Enantiomers of Pyridovericin and Mappicine,” Curran and coworkers showed that by tagging two enantiomeric starting materials, a “quasiracemic” mixture could be made. After several synthetic steps, the mixture was separated by FluoroFlash™ HPLC to deliver both product enantiomers.
This is the simplest application of a powerful technique called fluorous mixture synthesis (FMS) in which up to 7 substrates may be tagged, mixed, reacted as a single mixture through several synthetic steps, and separated by fluorous HPLC. The result is pure compounds, predictably eluted and identified based on fluorous tag length. A detailed application of FMS can be found in a Journal of the American Chemical Society article entitled, “Solution-Phase Preparation of a 560-Compound Library of Individual Pure Mappicine Analogues by Fluorous Mixture Synthesis.”
Fluorous Catalysts Ease Product Separation
Homogeneous catalysts are useful tools in organic synthesis, but often removal of such catalysts from the desired products requires time-consuming purification steps. For high-throughput synthesis, quick and reliable methods to isolate the product are critical. Pozzi and coworkers recently employed a lightly fluorinated chiral cobalt-salen complex for hydrolytic kinetic resolution of racemic terminal epoxides. The fluorous-tagged catalyst used was readily soluble in common organic solvents and the reactivity and enantioselectivity in the reactions investigated were comparable to those obtained with non-fluorinated catalysts.
Pozzi and coworkers reported that the use of a lightly fluorinated catalyst in combination with fluorous SPE (loading of the reaction mixture onto fluorous silica gel and elution with a ‘fluorophobic’ solvent) facilitated the isolation of desired products: “Solid-liquid extraction was found to be the quickest and operationally simplest way to get rid of the catalyst: it did not require the use of a fluorous solvent and could be useful in parallel synthesis.” Combining a lightly fluorinated catalyst withFluoroFlash®SPE delivers a practical solution to simplify the isolation step in homogeneous catalytic reactions and deliver ‘catalyst-free’ products.
Seeking Scientists
Ready to work in an exciting and challenging new area of chemistry for an emerging leader in the chemical technology industry? If so, FTI is currently seeking Bachelor, Master’s and Ph.D. scientists with experience in synthetic organic chemistry, medicinal chemistry, library generation, process R&D, or process chemistry. Click here to submit your resume today!
For further information please contact Dr. Philip E. Yeske at 412-826-3051. We value your privacy. To learn more about how FTI uses personal information, click here. To unsubscribe from this newsletter, please reply to this email with “unsubscribe” in the subject line.