Fluoro carbohydrates

In the course of studies on the reactivity30 of fluoro carbohydrates, the 3,4-isopropylidene acetals of 2-deoxy-2-fluorotetritols were obtained. These react with the Pnrdie reagents under mild conditions, to give the corresponding O-methyl derivatives. More-vigorous reaction-conditions cause expulsion of the fluorine atom, leading to 3,4-0-isopropylidene-l,2-di-0-methyl-DL-tetritols. Mild oxidation of 2-de oxy-2-fluoro-3,4-0 -isopropyl ide ne-DL-ery thritol with barium... 

As in previous years, space prevents any detailed review of the continuing interest in biological F-19 NMR. Here we sununarize the available data for the large biological molecules and their interactions, while data for the smaller molecules, such as fluoro carbohydrates and steroids, are found in the preceding tables. 

Hagiwara T, Kijima-Suda I, Ido T, Ohrui H, Tomita K (1994) Inhibition of bacterial and viral sialidases by 3-fluoro-V-acetyIneuraminic acid, Carbohydr Res 263 167-172 Haskell TH, Peterson FE, Watson D, Plessas NR, Culbertson T (1970) Neuraminidase inhibition and viral chemotherapy, J Med Chem 13 697-704 Hatakeyama S, Sugaya N, Ito M, Yamazaki M, Ichikawa M, Kimura K, Kiso M, Shimizu H, Kawakami C, Koike K, Mitamura K, Kawaoka Y (2007) Emergence of influenza B viruses with reduced sensitivity to neuraminidase inhibitors, JAMA 297 1435-1442 Hay AJ (1992) The action of adamantanamines against influenza A viruses inhibition of the M2 ion channel protein, Semin Virol 3 21-30... 

In the pentose series, attack has also been observed to occur mainly from the less-hindered side of the double bond, as in the addition of trifluoro(fluoroxy)methane to di-O-acetyl-D-arabinal. Trifluoromethyl 3,4-di-0-acetyl-2-deoxy-2-fluoro-/3-D-arabinopyranoside and 3,4-di-0-acetyl-2-deoxy-2-fluoro-/J-D-arabinopyranosyl fluoride were obtained,72,74 together with a very small proportion of 3,4-di-0-acetyl-2-deoxy-2-fluoro-a-D-ribopyranosyl fluoride.74 With di-O-acetyl-D-xylal, however, the lyxose derivatives were mainly obtained.72,73 The suggestion has been made73 that the greater conformational mobility of pentopyranoses results in a preponderance of the C d) conformer of the D-lyxose derivatives,72,73 such that F-l and CFsO-l are axially disposed. For further reactions of unsaturated carbohydrates with tri-fluoro(fluoroxy)methane, see Section 11,9. 

The reaction232-235 (see also Ref. 236) of 1-diazoketones with hydrogen fluoride that affords 1-fluoro ketones has also been applied to carbohydrates, with, however, no success. Treatment of 3,4-di-O-benzoyl-1-deoxy-l-diazo-D-gfycero-tetrulose with hydrogen fluoride in ether mainly afforded 3,4-di-O-benzoyl-D-gfycero-tetrulose, whereas, with hydrogen bromide and chloride, 3,4-di-O-benzoyl-l-bromo-l-deoxy-and 3,4-di-O-benzoyl-l-chloro-l-deoxy-D-gfycero-tetrulose, respec-... 

The Arbuzov reaction has been applied for the synthesis of fluorinated carbohydrates. 1,2 3,4-Di-O-isopropylidene-a-D-galactopyran-ose 6-(N,N-diethyl-P-methylphosphonamidite) was treated with ethyl fluoroacetate, to afford 6-deoxy-6-fluoro-l,2 3,4-di-O-isopropylidene-a-D-galactopyranose in 19% yield.241 The corresponding 6-deoxy-6-fluoride was obtained in 60% yield by treatment of l,2 3,4-di-0-isopropylidene-a-D-galactopyranose 6-(dipropylphosphinite) with hexafluoropropene.242 The mechanism of this reaction has been discussed.243,244 In contrast, treatment of 1,2 -.3,4-di-O-isopropylidene-a-D-galactopyranose 6-(tetraethylphosphorodiamidite) with benzoyl fluoride yielded the corresponding 6-benzoate, not the 6-deoxy-6-flu-oride expected.245... 

The availability, in gram quantities, of the fluorinated carbohydrates thus far synthesized has also made possible their use as starting materials for the synthesis of other analogs and intermediates for example, the preparation of 3,5-dideoxy-3,5-difluoro-D-xylose from 3-deoxy-3-fluoro-D-xylose,88 which is itself preparable from 3-deoxy-3-fluoro-l,2-0-isopropylidene-a-D-glucofuranose. Electrolytic oxidation of 3-deoxy-3-fluoro-D-glucose afforded, after treatment with an acidic... 

Several enzymatic procedures have been developed for the synthesis of carbohydrates from acyclic precursors. Aldolases appear to be useful catalysts for the construction of sugars through asymmeteric C-C bond formation. 2-deoxy-KDO, 2-deoxy-2-fluoro-KDO, 9-0-acetyl sialic acid and several unusual sugars were prepared by a combined chemical and enzymatic approach. Alcohol dehydrogenases and lipases have been used in the preparation of chiral furans, hydroxyaldehydes, and glycerol acetonide which are useful as building blocks in carbohydrate synthesis. 

A. F. Hadfield, L. Hough, and A. C. Richardson, The synthesis of further analogues of trehalose containing fluoro and amino substituents, Carbohydr. Res., 80 (1980) 123-130. 

S. M. Andersen, M. Ebner, C. W. Ekhart, G. Gradnig, G. Legler, I. Lundt, A. E. Stiitz, S. G. Withers, and T. Wrodnigg, Two isosteric fluorinated derivatives of the powerful glucosidase inhibitors, 1-deoxynojirimycin and 2,5-dideoxy-2,5-imino-D-mannitol Syntheses and glycosidase inhibitory activities of l,2,5-trideoxy-2-fluoro-l,5-imino-D-glucitol and of l,2,5-trideoxy-l-fluoro-2,5-imino-D-mannitol, Carbohydr. Res., 301 (1997) 155-166. 

In a series of papers, Kent and coworkers reported on the synthesis of the racemic 2-fluorotetritols and 2-fluoropentitols, and related carbohydrates from simple, non-carbohydrate precursors containing a fluorine atom in the carbon chain. Thus, synthesis of 2-deoxy-2-fluoro-DL-erythritol (537) and its threo isomer (538) was accomplished303 by vigorous reduction of ethyl ethoxalylfluoroacetate (536) with lithium... 

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