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Dear Friends of Fluorous,
Spring has arrived all over the world, and so has our March Newsletter. As usual, we have summarized the “latest and greatest” from the fluorous research community, while also delivering practical guidance for the fluorous end-user. This month you’ll find new products and new applications, as well as a sweet spring discount offer for our many friends in academia. Read on to find out more, and as always, be sure to let us know how we can help with your synthesis, separation and immobilization challenges.
Sincerely,
Philip E. Yeske
President & CEO
Product Promotion for our Academic Colleagues
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 how fluorous chemistry can make your daily work easier and more efficient. Place an order anytime during the month of April and a 20% discount will be applied to any purchase order of fluorous reagents; just ask for the April Academic Discount.
Fluorous Soluble Supports Used in Preparing Molecular Imaging & Therapy Agents
Dr. John Valliant and colleagues at McMaster University have reported a new strategy utilizing fluorous soluble supports for the synthesis and purification of "precursor-free" radiopharmaceuticals [1] The Valliant group used a fluorous tin species in the synthesis of 125I labeled benzamides that are currently being investigated as imaging agents for melanomas. Fluorous tin-tagged benzoates were converted to activated esters and reacted with amines to provide a fluorous tagged benzamide. The 125I was then introduced in a final iododestannylation step. Intermediates were readily purified by fluorous liquid-liquid extraction (F-LLE) while the displaced fluorous tag was removed by fluorous-solid phase extraction (F-SPE) to give the desired radiolabeled compounds in >98% purities. The fluorous approach has several advantages over previously reported solid supported approaches, including complete characterization of intermediates using traditional analytical techniques, favorable solution-phase reaction kinetics, facile reaction monitoring, and good stoichiometric control. As noted by the authors, the fluorous tagging strategy described can be used in the synthesis of radiopharmaceutical compound libraries with high effective specific activities. FTI offers a range of fluorous tin derivatives along with all the tools necessary for fluorous separations.
New Fluorous Protecting Groups for Peptide & Oligosaccharide Synthesis
Recently two separate reports of peptide and oligosaccharide synthesis using fluorous protecting groups have been published. Manzoni and Castelli [2] reported the synthesis and use of a new light fluorous amine protecting group, dubbed Froc, which is analogous to conventional Troc. This versatile tag was used in solution phase peptide and carbohydrate synthesis with tagged intermediates readily purified by F-SPE. At the end of the synthesis the tag was removed under reducing conditions. Fustero and colleagues at the University of Valencia meanwhile have developed a new tag, F-TMSE [3] for the protection of the C-terminus. The F-TMSE was evaluated in the synthesis of small peptides and found to be compatible with both Fmoc and Boc based peptide syntheses. The F-TMSE tagged peptide was readily detagged with TBAF with no epimerization or other side reactions being observed.
Both Froc and F-TMSE offer all the expected benefits of fluorous based solution phase chemistry, including favorable reaction kinetics, easy purification of intermediates by F-SPE, and the ability to monitor reactions using standard techniques. FTI offers a full line of reagents, tags, and purification media for peptide synthesis, including F-Fmoc tagging reagents, F-Fmoc, F-Boc, and F-Z amino acids, and F-SPE cartridges. If you are interested in either of these compounds, send us an email.
Learn More about Fluorous Chemistry:
The Royal Society of Chemistry
9 May 2006 - High Throughput Medicinal Chemistry Symposium
Prof. Dennis Curran, founder of Fluorous Technologies Inc., will be presenting: "Fluorous Mixture Synthesis Approaches to Natural Product Stereoisomer Libraries” at The Royal Society of Chemistry's "High Throughput Medicinal Chemistry Symposium" in London on May 9, 2006. To view further details about this conference, please go to http://www.mmsconferencing.com/htmc06.html
Fluorous-Supported Scavengers
In a recent paper published in a special issue of Molecular Diversity [4] on “Synthesis and purification using bound reagents, 
scavengers and SPE”, scientists from Fluorous Technologies, Inc. reported the comparison experiments using fluorous and polymer-supported reagents and scavengers. The Scheme shows that when equal molar amounts of material are used, reactions with the fluorous scavenger (C8F17CH2CH2SH, green line) proceed much faster than reactions using the solid-supported scavenger (Si-CH2CH2CH2SH, red line). Unlike solid phase scavengers 
which often require large excesses due to unfavorable heterogeneous reaction kinetics, fluorous scavengers can be used in near-stoichiometric amounts. FTI provides a variety of nucleophilic and electrophilic scavengers to meet your synthetic requirements. These can then be removed using fluorous solid phase extraction techniques (F-SPE).
FTI Open Forum: Your Feedback, Your Questions
In our January issue of the FTI Technical Newsletter we introduced an “Open Forum” where we asked for your feedback or for your questions regarding the application of a fluorous reagent or how to use a fluorous sorbent. We did receive feedback from customers and questions, some of which you will see printed below. We appreciate and continue to seek the input of our colleagues and welcome you, our reader, to submit ideas for future newsletters. This newsletter is our vehicle to provide our customers with the most current developments happening both at Fluorous Technologies and in the fluorous chemistry research community. Is there a specific topic that you would like to see us cover? Do you have a paper that you recently published that you would like to see reviewed? Is there a presentation for which you would like a wider audience? Email them to us. We will personally reply to all comments and questions received in a timely manner and publish as many as we can.
Customer Testimonials:
From a Scientist at Duke University using Fluorous Mitsunobu Reagents: “I cannot describe my glee at the simplicity of its use and how the use of fluorous agents has simplified my purification. Given the complexity of the Mitsunobu with its many reagents and by products, this is indeed a most useful methodology. I only wish I had used it a few years earlier when the commercial reagents had come available... I'd highly recommend it to anyone else struggling with these sorts of reactions.”
From a West Coast Scientist using Fluorous Proteomics Reagents: “As a lab we have decided that we will be using Fluorous-tools rather than biotin in the foreseeable future, its so much cleaner and easier to work with!”
Fluorous Q&A:
"What size fluorous tag is most commonly used and why?”
FTI Staff Scientist, Mike Petro offers this answer:
While the size of the fluorous tag will not affect reagent reactivity, it will affect the retention on the fluorous separation media. For most applications we recommend using an Rf8 (C8F17) tag, since it has the best balance of solubility and retention on the fluorous silica gel. For applications that require greater water solubility such as proteomics, we recommend Rf6 (C6F13) tags. The fluorous reagents with a single Rf8 tag are easily retained on the F-SPE cartridge and will elute off the cartridge as described in our Fluorous SPE Application Note. If you are unsure of which tag you need, give us a call and we will be more than happy to help you pick the tag that is right for your application.
References:
[1] Donovan, A.; Forbes, J.; Dorff, P.; Schaffer, P.; Babich, J.; Valliant, J.; “A New Strategy for Preparing Molecular Imaging and Therapy Agents Using Fluorine-Rich (Fluorous) Soluble Supports” J. Am. Chem. Soc. 2006, 10.1021/ja0600375
[2] Manzoni, L.; Castelli, R.; “Froc: A New Fluorous Protective Group for Peptide and Oligosaccharide Synthesis” Org. Lett., 2006, 8, 955-957
[3] Fustero, S.; Sancho, A.G.; Chiva, G.; Sanz-Cervera, J.F.; del Pozo, C.; Acena, J.L.; “Fluorous (Trimethylsilyl)ethanol: A New Reagent for Carboxylic Acid Tagging and Protection in Peptide Synthesis” J. Org. Chem., 2006, 10.1021/jo052569u
[4] Chen, C. H.-T.; Zhang, W. “Fluorous Reagents and Scavengers versus Solid-Supported Reagents and Scavengers, A Reaction Rate and Kinetic Comparison” Molecular Diversity 2005, 9, 353-359.