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CEOverture...
Dear Friends of FTI,
“The Ides of March” have passed us by and now “March Madness” reigns supreme in America. Regardless of whether you do or don’t have a rooting interest in US college basketball, it’s a great time of year as winter slowly evolves into spring here in the north. Fluorous technology also continues to evolve, and in the most recent issue of Sigma-Aldrich’s ChemFile (Volume 7, Number 2) you’ll find a nice summary of the utility of fluorous techniques in peptide synthesis. Sigma-Aldrich is a preferred distributor of FTI products, and this latest ChemFile includes a complete listing of fluorous products available for peptide synthesis as well as proteomics. Lastly, we can’t help you with that NCAA bracket you’re stuck with now- better luck next year in the office pool.
Cheers,
Phil
Philip E. Yeske
President & CEO
Fluorous Mitsunobu Aids Research for Potential Antitubercular Agent
Dr. Courtney Aldrich and colleagues at the University of Minnesota and National Institute of Allergy and Infectious Diseases recently reported their progress on the development of a new class of antitubercular agents which inhibit the enzyme MbtA and disrupt the biosynthesis of mycobacterium(1). The targeted molecules are adenosylated β-ketosulfonamides formed by the Mitsunobu reaction of the sulfonamide with a protected adenosine. Initial attempts at the Mitsunobu reaction were unsuccessful, but by altering the protecting group on the adenosine and optimizing the DIAD addition rates, excellent conversions (82%) were realized. However, difficulty was encountered with the separation of the pure compound from the crude reaction mixture which required multiple chromatographic separations. To simplify the isolation of the desired compound, the authors employed the Fluorous Mitsunobu approach using F-DIAD and F-TPP which provided the desired compounds in 85% yield using a simple fluorous solid phase extraction (F-SPE) rather than multiple chromatographies. The work reported by Dr. Aldrich is an excellent example of the value of fluorous techniques. Not only was the purification of the reaction simplified, but the yields observed and conditions used were essentially identical to the traditional Mitsunobu, thereby minimizing reaction method development. Through the use of F-TPP, F-DIAD and F-SPE combined with optimized reaction conditions, the desired compound was obtained faster and with less effort.
Organocatalysis with a Fluorous Tag
Expanding upon their previous work on asymmetric imine reduction, Malkov, Kočovský, and colleagues at the University of Glasgow have reported the use of fluorous organocatalyst mediated Cl3SiH reductions. The valine derived anilide organocatalysts were produced by attaching a fluorous domain to the appropriate phenol either by a Mitsunobu reaction or phase transfer catalysis with a fluorous ethyl alcohol. The fluorous organocatalysts were used in ketimine reductions and found to produce secondary amines in good yields and enantiomeric excesses comparable to that found with the non-fluorous tagged analogs. Product purification and catalyst recovery were greatly simplified through the use of fluorous solid phase extraction (F-SPE), eliminating the need for column chromatography. The recovered fluorous catalysts were reused up to 5 times with only a marginal affect on both reactivity and selectivity. The authors conclude that given the solution phase nature of the chemistry and the ease of isolation via F-SPE, that the use of fluorous organocatalysts is well-suited to small-scale parallel chemistry.
Product Promotion for the Fluorous-Intrigued
Have you wondered if fluorous chemistry really does make a chemist’s life easier? As illustrated by the articles highlighted above, the use of fluorous chemistry really does make your research work easier and more efficient. Here's your chance to take advantage of a great sales promotion on any of the fluorous reagents offered on our website catalog, and in the process, see for yourself how easy life can be. Well, at least in the lab. Place an order from March 20th to April 20th and a 25% discount will be applied to any purchase order of fluorous reagents totaling USD500 or more; just ask for the “fluorous curious” Discount.
233rd ACS National Meeting, Chicago - March 25-29
The Spring ACS meeting will be March 25 – 29 in Chicago, IL and several posters and presentations will highlight the use of fluorous chemistry in research applications. Professor Nicola Pohl and her group at Iowa State University will be presenting 6 posters and presentations on the use of fluorous chemistry in carbohydrate research. Additional posters and presentations will focus on the use of fluorous tagging strategies and fluorous biphasic reactions. Access the details on these posters or presentations through the ACS Technical Program schedule and search for “fluorous”. Listed here are some examples of the posters and presentations that will be given.
Incorporation of reducing saccharides into carbohydrate microarrays using synthetic fluorous tags Poster Presented by: Guo-Song Chen and Nicola L. Pohl; Iowa State University, Department of Chemistry and the Plant Sciences Institute Time/Location: 6:00 PM-8:00 PM, Tuesday, 27 March 2007 Hyatt Regency Chicago -- Riverside Center
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Carbohydrate microarrays can map out key interactions of carbohydrates and proteins in a high throughput manner, but require a range of sugars for their optimal use. Recently we have demonstrated a simple method to synthesize oligosaccharides using fluorocarbon tags that also allows the direct formation of microarrays by noncovalent fluorous-fluorous interactions. Here we present chemistry that allows the expansion of this fluorous-based microarray technology to sugars isolated from natural sources. Specifically, the synthesis of new fluorous tags and their reaction with reducing sugars is reported along with their incorporation into microarrays and screening against lectins.
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Dithiocarbamate-, dithiobenzoate-, and nitroxyl- based free radicals in dynamic combinatorial chemistry: Library generation and deconvolution
Poster Presented by: David Crich, Albert A. Bowers, and Daniel Grant; University of Illinois at Chicago Department of Chemistry Time/Location: 8:00 PM-10:00 PM, Wednesday, 28 March 2007 Hyatt Regency Chicago -- Riverside Center
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Two methods for the generation of pre-equilibrated dynamic combinatorial libraries (pDCLs) via radical exchange reactions will be described. In the first, alkyl substituents are traded between imidazolone dithiocarbamates and dithiobenzoates under action of a catalytic amount of azo-initiator. The effectiveness of the process is demonstrated by NMR characterization of the library itself and by GC-MS analysis of the individual compounds. In the second method, cyclic and acyclic alkoxylamines undergo equilibration in accord with the persistent radical effect (Fischer-Ingold effect). Deconvolution is achieved by means of a fluorous tagging/fluorous chromatography strategy that is compatible with conditions of library preparation. The later compounds represent analogues of the new class of HIV integrase inhibitors (e.g. NBD 556/557 and BMS 378806).
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Oligonucleotide Purification & Fluorous - A Perfect Match
FTI's partner organization in the oligonucleotide field, Berry & Associates, will be exhibiting at the upcoming Association of Biomolecular Resource Facilities conference in Tampa, Florida (ABRF 2007). The good folks from Berry will be manning their booth #415 from April 1st to 3rd, and are ready to tell you about how fluorous technology facilitates biopolymer purification.
A "Thank You" and a Reminder from Customer Service
We really appreciate each and every customer- and thank you for your business. For all orders received, a confirmation number, pricing verification, and lead time will be provided by FTI to the purchasing department within 24 hours of the receipt of the order. If you would like a confirmation of your order being placed with us, please instruct your purchasing department to provide your email address to us. If within 24 hours you do not receive that information, please contact your purchasing department or FTI to ensure that your order is fulfilled in a timely manner. We are always looking for ways to serve you better and will do whatever we can to ensure your complete satisfaction.
References:
1. Vannada, Jagadeshwar; Bennett, Eric M.; Wilson, Daniel J.; Boshoff, Helena I.; Barry, Clifton E.; Aldrich,
Courtney C., Org. Lett., 2006, 8(21), 4707-4710.
2. Malkov, Andrei V.; Figlus, Marek; Stončius, Sigitas; Kočovský, Pavel J. Org. Chem. 2007, 72, 1315-1325.