Heavily Fluorinated Sugar Analogues

Dimagno, US Patent 6,392,032 (May 21, 2002) Assignee Board of Regents University of Nebraska-Lincoln Utility Anti-Neoplastic Agents 

V- Ruthenium(IV)oxide, acetonitrile, water, carbontetrachloride, sodium periodate 

4-Hexafluoropentanoate (0.47 mmol) was dissolved in 250 ml ethyl alcohol containing 5 ml concentrated H2SO4 and refluxed 7 days using a soxlet extractor and 65 pellets 1.4 A molecular sieves. Ethyl alcohol was then removed and the residue neutralized to pH 7 using NaHCOj before adding water. The product was extracted 3 times with 100 ml diethyl ether, washed, and the product isolated in 81% yield. H-NMR data supplied. 

In the absence of light, furan (12.4 mmol) was dissolved in 30 ml THE cooled to —78°C, 3 ml 2.5 M n-butyllithium added, and the mixture stirred 3 hours. The product from Step 1 (13.8 mmol) dissolved in 100 ml THE was added over 15 minutes and then stirred 30 minutes. The solvent was removed at ambient temperature, the mixture purified by chromatography on silica gel using hexanes/EtOAc, 9 1, and the product isolated in 39% yield. H- and F-NMR and elemental analysis data supplied. 

NaBH4 (9.25 mmol) was added to a solution of the product from Step 2 (4.81 mmol) dissolved in 100 ml methyl alcohol at 0°C. After 3 hours, the solvent was removed and the residue acidified to pH 2 using 2 M HCl. The mixture was then neutralized with NaHCOj and the product extracted 3 times with 50 ml diethyl ether. The product was isolated as an oil, re-crystallized in hexane/chloroform, 3 1, and isolated in 96% yield as 1 1 trans/cis isomers, mp = 89-90°C. H- and F-NMR and elemental analysis data supplied. 

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