November 2009 Technical Newsletter
November 2009 Fluorous Technical Newsletter
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Small molecules may be small, but they are a huge part of the life sciences landscape. The roots of Fluorous Technologies are in synthesis and purification of small molecule drug candidates and we’re proud to offer a large selection of FluoroFlash® products to support the research effort of medicinal chemists around the world. While we’ve spent a lot of time in this forum talking about and promoting biomolecule and life science applications, small molecule chemistry remains an important part of our business. Today we thought we’d share a few recent highlights from the small molecule realm where fluorous technology played an integral role in making the research a success. Hope you find the information useful and stimulating.
Cheers,
Philip E. Yeske
President & CEO
Fluorous Technologies Inc.
Fluorous Technologies Awarded Two Grant Supplements
The NIH General Medical Sciences section has awarded Fluorous Technologies Inc. two supplements to ongoing grants. The first supplement will resupply compounds to the NIH’s Molecular Libraries Small Molecule Repository (MLSMR), a collection that is made available to NIH sponsored screening centers. Over the last two years, we have deposited into the MLSMR fifteen libraries of novel heterocycles produced using fluorous methods. We are happy to learn that these compounds are being screened and are producing hits, thereby requiring resupply at larger quantities. The value of using fluorous methods in small molecule library production is exhibited in both the initial synthesis and the follow-up. Not only can novel molecules of interest be prepared efficiently and in high purity, but resynthesis and scale-up of libraries is easy due to the reproducibility and scalability of fluorous solution phase chemistry.
The second award supplements a STTR grant for fluorous methods for oligosaccharide and peptide microarrays, developed jointly by researchers at Fluorous Technologies and Iowa State University. Initial results have just published from this grant using fluorous methods for peptide synthesis and microarray formation. With the awarding of the supplement, we will be expanding the research to include mixed microarrays with peptides and oligosaccharides spotted on a single surface.
Synthesis of a Benzodiazepinedione Library
A group of researchers led by Prof. Bing Yan recently published their use of fluorous tags in benzodiazepinedione synthesis. The general reaction scheme is shown above and highlights some of the ways fluorous techniques can facilitate parallel synthesis efforts. In multi-component reactions, for example, fluorous tags make it easy to isolate the desired product from all other components. The use of microwave chemistry in the Suzuki reaction demonstrates the complementarity of fluorous techniques with various chemistries and technologies. Additionally, fluorous solid phase reaction (FSPE) after each step provides intermediates and final products in very good to high purities (~90%). This results in greater quantities of each compound being isolated and a greater percentage of library members being recovered after final HPLC purification. To learn more about this article, please read our F-Blog summary.
SAR Studies on Resorcylic Acid Macrolactones
Besides using a single tag for parallel synthesis, multiple fluorous tags of different lengths can be used in fluorous mixture synthesis (FMS). Prof. Nicolas Winssinger’s group at the University of Strasbourg has recently published the synthesis of a library of resorcylic acid macrolactones using FMS. The route is similar to what they reported in 2007 for the total synthesis of radicicol A using a single fluorous PMB tag, but by using FMS have now expanded the chemistry to library synthesis. As depicted below, 27 acyclic precursors were obtained after fluorous demixing.
The macrolactonization was then conducted using a fluorous Mitsunobu followed by FSPE. Further functional group manipulation resulted in a total of 50 analogs being produced. These analogs were then screened against a panel of kinases to provide SAR data for these biologically interesting compounds. This paper provides a great example of how fluorous techniques can be easily modified to fit the needs of the project. In this case, transforming a total synthesis to a library synthesis with minimal development.
Fluorous.com Update
The new version of fluorous.com has now been up and running since June and from all indications the redesign has been a success. The website was designed to feature applications based on our products and fluorous techniques. Choose your research area of interest to explore how fluorous can best fit your needs. For each application we have provided related product listings and links to additional information and resources.
You can browse product listings in our Support and Catalog section by clicking the Product Listings button in the left-hand navigation bar. If you already know the product that you would like to use, enter the part number into the search bar at the top right corner of every page to retrieve the latest product information.
Our goal is to be the most complete and up-to-date online information resource for fluorous chemistry while also providing a site for new users to learn more about fluorous techniques. We continue to expand the presentations section and we frequently publish posts in our technical blog, F-Blog, and the more general News section.
Thanks for the feedback and please continue to let us know how to better your experience on fluorous.com.
The Fine Print
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, peptide and oligonucleotide production, and proteomics. For more information, please visit: http://fluorous.com
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.