| If your email does not support graphics, please access the web version of this technical bulletin. | 
|
Welcome to our January 2006 Technical Newsletter. In this issue, we have exciting news to share with you of new products for both the small molecule as well as the peptide chemistry communities. You’ll also find a summary of some recently published work utilizing fluorous chemistry out of the Merck Research Labs. Thanks for taking the time to look it over, and we hope you find it useful. We value your feedback, so please let us know if there is anything we can do to assist you with your job.
Sincerely,
Philip E. Yeske
President & CEO
Peptide Chemistry Unleashed - Fluorous Fmoc is HERE!
We announced in the December 2005 issue of our Technical Newsletter that fluorous Fmoc and Fmoc-tagged amino acids were Coming Soon! Well, that time has arrived and we are pleased to announce their release. This exciting new product family of fluorous tagging agents and their tagged amino acid counterparts is the direct result of a clear message from the peptide research community - give us Fmoc! Well, we listened, and our development team came through. They even developed new trityl tagging reagents for side-chain protection. All the details are below or can be conveniently accessed through our website. There you can read about the utility of fluorous technology in peptide chemistry, search our initial product offering, place an order, or even provide feedback to us on your custom needs.
The Workhorse of Peptide Chemistry
Our first new offerings are the reagents to introduce fluorous Fmoc onto an amino acid or peptide. F-Fmoc-OSu and F-Fmoc-Cl are handled just like their non-fluorous equivalents, delivering an F-Fmoc that is base labile and removed just like conventional Fmoc. Ideal for N-terminal tagging in solid phase peptide synthesis (SPPS) - click here for details on the utility of fluorous chemistry in peptide synthesis and separation.
Fmoc-tagged Amino Acids - Ready to Go!
Prefer to work with pre-tagged amino acids? No problem! Our new line of fluorous Fmoc-tagged amino acids builds off the success of fluorous Z-tagged amino acids. Perfect for coupling as a final residue during SPPS, followed by quick and easy fluorous purification after cleavage from the resin and standard base-promoted deprotection. Need Boc-protected amino acids? We have those too! Check out our initial offering, and if you don’t see what you’re looking for, just send us a message - we’d be happy to provide a quote.
You Say Tri-tyl, I say Try-tyl...
Regardless of how you pronounce it, several fluorous versions of trityl chloride tagging reagents (and their precursor alcohols) are now available for the protection of alcohols, amines, and carboxylates. These include F-Tr, F-MMT, and F-DMT products that are analogous to conventional trityl, monomethoxy trityl, and dimethoxy trityl products, respectively. Each of the fluorous versions reacts just like its non-fluorous counterpart- going on and coming off. Each of these groups are acid labile with the relative rate of deprotection being F-Tr < F-MMT < F-DMT. The F-DMT group has been used in oligonucleotide synthesis followed by purification by F-SPE (1).
1. Pearson, W.H.; Berry, D.A.; Stoy, P.; Jung, K-Y.; Sercel, A.D. J. Org. Chem. 2005, 70, 7114-7122.
Fluorous Scavenging in Diversity-Oriented Synthesis
In two separate publications, C. Lindsley and co-workers at Merck and Co. recently reported using a fluorous thiol as a nucleophilic scavenger of a benzyl bromide during the preparation of libraries of quinoxalines (Bioorg. Med. Chem Lett. 2005) and unnatural canthine alkaloids (Tetrahedron Lett. 2005, 46, 2779). In each case the initial step of the synthetic route was the reaction of excess benzyl bromide with either a primary or secondary amine. The excess bromide was then scavenged with a fluorous thiol and the desired product was isolated by F-SPE. Average purity was 95% for over 200 reactions. It was noted that polymer supported thiol failed to provide product in sufficient purity.
Ask FTI - An Invitation to Help Us Create an "Open Forum" Section
The FTI Technical 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. The majority of our content is derived from the staff at FTI. We would like to change that and welcome you, our reader, to submit ideas for future newsletters. 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? Do you have questions regarding the application of a fluorous reagent or how to use a fluorous sorbent? 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.
One question we are frequently asked is:
“How much sample can I put onto a Fluorous SPE cartridge or a Fluorous HPLC column?
FTI Staff Scientist, Yimin Lu offers this answer:
For F-SPE cartridge loading, volume is more critical than mass. For MeOH, ACN, DCM or THF, use less than 10%, i.e. less than 0.2 mL solvent for a 2 g cartridge. For DMF, you can use up to 50%, i.e. 1 mL for a 2 g cartridge. For mass loading, we have tested 20% mass loading and no breakthrough was observed. We are currently working on a new SPE procedure which is very promising for using a large amount of loading solvent.
For an analytical fluorous HPLC column, make your sample to a concentration of 1mg/mL and inject 5 µL. For a semi-preparative fluorous HPLC column, up to 100 mg mixture has been loaded onto a 4.6x250mm column while still maintaining good separation during demixing of a mixture containing multiple fluorous species of different fluorine contents.
Latest Review of Light Fluorous Synthesis
Dr. Dennis Curran, founder of Fluorous Technologies, Inc., recently authored a comprehensive review on light fluorous chemistry which was published in Aldrichimica ACTA Vol. 39, No. 1. 2006. Dr. Curran’s paper “Organic Synthesis with Light-Fluorous Reagents, Reactant, Catalysts and Scavengers” covers recent developments in the use of light-fluorous materials for the synthesis of small organic molecules as well as biomolecules.
2006 Fluorous Technologies Catalog
Happy New Year! Happy New Catalog! With so many new products and applications, this year we made some changes to our catalog, including new product sizes- but no price increase! We have also worked to improve product descriptions and update references for many of our compounds. Be sure to take a look at the on-line catalog pages, or download your own copy!