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CEOverture...
A belated Happy New Year to all of our readers from the team at FTI! We appreciate all the support in 2006, and look forward to the opportunity of even more interaction in 2007. It’s hard to believe that almost 1/12th of the year has already gone by, so let’s get down to business with our first Technical Newsletter of 2007. Today we’re highlighting a few recent articles on both heavy and light fluorous chemistry, all of which take advantage of fluorous tags and simple, robust separation protocols. We’ve even decided to offer a promotion on select tag and separation products, so be sure to read all the way through to the end. May your 2007 be a happy, healthy and prosperous year. Let us know how we can be of assistance with your research.
Cheers,
Phil
Philip E. Yeske
President & CEO
Aminoglycoside Synthesis Using Fluorous Liquid-Liquid Extraction (F-LLE)
Researchers at the Noguchi Institute[1] have recently reported the use of a heavy fluorous Cbz-type tag in conjunction with fluorous liquid-liquid extraction (F-LLE) for the synthesis of aminoglycans, an important class of compounds. As depicted below, the modified Cbz(HexF) tag was first glycosylated to provide fluorous glycoside A. Deprotection provided alcohol B and glycosylation provided fluorous disaccharide C. Each of the fluorous tagged intermediates A, B, and C were isolated by simple fluorous liquid-liquid extraction between FC-72 (perfluorohexanes) and an organic solvent. Treatment of C with NaOMe followed by F-LLE provided detagged disaccharide D as a mixture of anomers in the organic layer and the fluorous HexF residue in the fluorous layer. The anomers were separated by HPLC followed by hydrogenation to provide each of aminoglycoside anomers E in pure form. The work reported not only demonstrates the utility of F-LLE in fluorous separations, but is also another great example of fluorous tagging strategies where the fluorous tag serves as a solution phase equivalent to traditional solid phase chemistry. Alternatively, light fluorous tags containing only one fluorous chain can be used with fluorous solid phase extraction (F-SPE) as the separation technique. FTI provides numerous light fluorous versions of traditional protecting groups which can be used in conjunction with fluorous solid phase extraction (F-SPE).
Polymer Chemistry and Fluorous
Conjugated oligothiophenes are novel organic materials that have excellent potential for semiconductor and optoelectronic applications. Prof. Michael Turner and his group at the University of Manchester[2] recently reported a new reaction sequence for the synthesis of fluorous-modified oligothiophenes by α-bromination of fluorous thiophenes and microwave-assisted Stille cross-coupling reactions. The fluorous reaction mixtures were readily purified by fluorous solid-phase extraction (F-SPE). Fluorous oligomers up to 4 thiophene units long have been prepared by this new protocol.
The Fluorous Parallel Approach to High Throughput Purification
Sclerotigenin belongs to the benzodiazepine-quinazolinone natural alkaloid family which has attractive biological activities. In a joint paper published by scientists from Neurocrine Biosciences and FTI, a new synthetic protocol for solution-phase parallel synthesis of 9 sclerotigenin analogs (5 to 20mg scale) is introduced[3]. A fluorous benzyl group (F-Bn) is doubly employed to protect amino esters as well as act as a phase tag to simplify reaction mixture purification. In the multi-step synthesis, most intermediate purifications were conducted by fluorous solid-phase extraction (F-SPE) yielding >90% purity without the need for additional chromatography. Other synthetic techniques such as sonication and microwave irradiation, completely compatible with fluorous technology, were used to improve the reaction efficiency. Similar chemistry has been applied to synthesize a benzodiazepinedione library containing several hundred compounds (finished compounds obtained at >3mg scale; >85% purity; >70% success rate) with this work presented at the 2006 ACS Meeting in San Francisco. The complete presentation is available on FTI’s website.
Sigma Aldrich Promotes Fluorous Technologies
Sigma-Aldrich now offers an even wider selection of products from Fluorous Technologies Inc. and is actively promoting fluorous chemistry and techniques through several of their publications. For example, a recent Sigma-Aldrich Cheminar was posted on “Fluorous Technologies: Synthesis, Separations, and Enrichment”. To review this Cheminar, click here.
Aldrichimica Acta highlighted a paper by Professor Dennis Curran, founder of Fluorous Technologies, Inc. on “Organic Synthesis with Light-Fluorous Reagents, Reactants, Catalysts, and Scavengers”. To review this paper, click here for the link.
Finally, ChemFiles devoted an issue to Fluorous Synthesis and Separation that serves as a useful primer on the technology, albeit somewhat dated (be sure to visit www.fluorous.com for the most up-to-date product and application information). Here is the ChemFiles link.
Simplify Your Chemistry, Save Some Money
Want to see for yourself how the use of fluorous tags and fluorous purification techniques can make your daily work easier and more efficient? Here's your chance to take advantage of a great sales promotion on a wide variety of fluorous tagging reagents and fluorous SPE cartridges. Place an order from now through Feb 28 and a 25% discount will be applied to any purchase order of these fluorous reagents and F-SPE cartridges; just ask for the “Simplify My Work” Promotion when you place your order.
Fluorous Tagging Reagents
F-Boc-ON F009003, F013003, F017003
F-Silane F009004, F013004, F017004
F-PMB Alcohol F009006, F013006, F017006
F-t-Butanol F009007, F013007, F017007
F-Cbz-OSu F009008, F013008, F017008
F-Benzyl Alcohol F009026, F013026, F017026
FluoMar® F009027, F013027, F017027
Fluorous SPE Cartridges 801-0027S-5, 801-0027S 20, 801-0058S-2, 801-0058S-10,
801-0109S-1, 801-0109S-5, 801-0209A, 801-0209B
References:
1. Mizuno, M. et al, Tetrahedron Lett. 47, 2006, 8831-8835.
2. McCairn, M. C.; Turner M. L. Tetrahedron Lett. 2007, 48, 1045-1047.
3. Zhang, W.; Williams, J. A.; Lu, Y.; Nagashima, T.; Chu, Q. Tetrahedron Lett. 2007, 48, 563-565.