C-Fructosides

The Lewis acid catalyzed C-glycosylation method is probably one of the most efficient to prepare C-glycosides of ketoses, the anomeric carbocation intermediate being in this case more stabilized by a further substituent. We applied this procedure to synthesize C-fructosides [15] (Scheme 8).The reaction of methyl... 

The above-mentioned procedure for the synthesis of C-fructosides has been used to synthesize the bisphosphono analog of / -D-fructose 2,6-bisphos-phate [ 16], which is, as reported in Sect. 2.3, an important activator of glycolysis and inhibitor of gluconeogenesis. To prepare the target molecule we first attempted the conversion of the firee hy iroxyl group of 21 into an iodide which in turn can be easily converted into a phosphonate. However, this conversion... 

Different electrophiles, such as I2, Br2, NBS, NIS, PhSeCl or metachloperoxy-benzoic acid have been used in the cyclization of glycoenitols [34], but the best stereochemical results have been obtained with mercuric salts and iodine. Iodine however can give rise to a debenzylation with formation of the more favored 5-member cyclization product. This is the case for 72 which, when treated with iodine, affords the C-fructosidic structure 83 [35] (Scheme 23). 

The reaction stereoselectively affords the 2 -R isomer as the major product (d.e. 33%). The absolute configuration of the 2 carbon was determined by NOESY analysis, in particular consistent n.0.e.s between H-l and H-l b and between H-l a and H-2 protons were observed. Treatment of 16 with zinc and acetic acid, afforded 17, that was transformed in the C-fiructoside 18 (Scheme 6). Compound 18 can be considered as an a- or a P-C-fructoside, in which both the hydroxymetyl arms can be further manipulated. An interesting example of this is the formation of the new spiro structure 20, as reported in Scheme 6. 

In the phosphonic add series, the isomeric analogues (1) and (2) of AT-acetyl-2-deoxyneuraminic acid have been prepared fi om A/ -acetylneuraminic acid, and the isosteric bisphosphono - analogue (3) of -D-fructose 2,6-bisphosphate has been synthesized from the C-fructoside (4). Chiral 1,6-diphosphine ligands (5) and (6) have been prepared fr-om D-mannitol and utilised unsuccessfully with Rh(I) in attempts to effect asymmetric hydrogenations. ... 

The fructosylation of elymoclavine (9) by C. purpurea was described in [42] (Fig. 8). This reaction is mediated by the transfructosylating activity of p-fructofur-anosidase in sucrose-containing media. Beside mono- (10) and difructoside, higher fructosides (tri- and tetra-) (11) are also formed [43] (Fig. 9). 

Glycosylating Claviceps strains (mostly C. fusiformis) produce most elymoclavine in the form of p-fructofuranosides, which complicates the isolation of elymoclavine. The hydrolysis of fructosides by HCl is not suitable for a large scale process due to the aggressive nature of the acid solution and losses of elymoclavine. A more elegant method is a bioconversion employing the high invertase activity... 

Of particular interest with respect to the mechanism of action of the enzyme is the finding by Bencovic et al. (23) that methyl fructoside 1,6-diphosphate does not protect the active site of the enzyme against acetylation by acetyl imidazole (see below) but instead increases the rate of the reaction. This suggests that the substrate induces a conformational change in the enzyme and further, since the methyl derivative is not hydrolyzed, that the hydroxyl group at C-2 may play a role in the catalytic mechanism. 

With long alkyl chain alcohols, the conversion of fructose with 1-octanol to octylfructosides was only 60%, but with 1-decanol and 1-dodecanol the conversion dropped to 40% due to competing of fructose ring opening. However, in 1,2-dimethoxyethane as solvent, a yield in dodecyl-D-fructosides of 60% was obtained after 1.5 h at 83 °C. 

Methyl 7 -D-fructoside was first made when Menzies89 dissolved D-fructose in methanolic hydrogen chloride and stopped the reaction when the [a]D reached a maximum (after about 30 minutes). The sirup obtained on removal of the methanol by distillation was partially soluble in ethyl acetate, leaving a residue with negative specific rotation, which was probably methyl D-fructopyranoside and unchanged D-fructose. From the ethyl acetate solution sirupy methyl 7 -D-fructoside, [c ]d +26.6° in water, was obtained. Schlubach and Rauchalles90 showed that this fructoside was only partially hydrolyzed by invertase. This enzymatic hydrolysis was further investigated by Purves and Hud-... 

Fructosylation of other alkaloids than elymodavine is complicated by the fact that (living) cells of C. purpurea also produce elymodavine, and this alkaloid competes with the introduced alkaloids for the fructosyl transfer. It was found that elymodavine has a higher affinity for the fructosyl transfer than other alkaloids (Table 1). Both the lowered yield and separation problems prevented us from obtaining lysergol and DH-lysergol fructosides. Less reactive alkaloids... 

Fig. 2. Influence of pH on elymoclavine fructosylation by C. purpurea cells, showing conversion to elymoclavine monofructoside (- -) and total elymoclavine fructosides (-0-)...

Synthesis of racemic ketohexosides, namely methyl a-sorboside, a-tagato-side, 3-fructoside, and a-psicoside was achieved in an analogous way, starting from the monobenzyl ether of 2,5-di(hydroxymethyl) furan.The inversion of configuration at C-5, necessary for completion of some of these syntheses, was performed at the stage of the unsaturated pyranoside by means of the benzoic acid-triphenylphosphine-ethyl azodicaiboxylate reagent. ... 

Quillet, M. Sur le Metabolisme Glucidique des Bryophytes. Presence de Poly-fructosides dans Certains Groupes d Hepatiques. C. R. Acad. Sci. Paris 232, 2475 (1956). 

D-Pructose, fruit sugar, or Icevulose, accompanies glucose in fruits, flowers, and their product, honey. It is obtained also from the hydrolysis of fructosides, the chief of which is sucrose, and from the polysaccharide, inulin. It crystallises with difficulty in fine, colourless needles, m.p. 110° C. Fructose differs from the other three fermentable hexoses in being a keto-sugar, or ketose, and in being tovo-rotatory, [a]j, = — 92 0°. It is much sweeter and more reactive than glucose. 

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