Ribose 2,3-dideoxy

Table 3). For example, arabinose and xylose differ from ribose only in the orientation of the 2 - and 3 -OH groups yet exhibit markedly different potencies. Whereas 9-(tetrahydrofuryl)-Ade ( SQ 22,536) and 9-(cyclopentyl)-Ade are without hydroxyl groups and are less potent, they offer metabolic and biochemical stability useful for many types of studies. It is, however, the removal of two of the hydroxyl groups, that elicits the largest improvement in inhibitory potency, in particular the 2, 5 -dideoxy- modification (Table 3). With these improvements in potency, these cell permeable compounds, in particular 2, 5 -dd-Ado, have become useful research tools and have been used to inhibit adenylyl cyclases and to lower cAMP levels and alter function in numerous studies in isolated cells or intact tissues. 

Adition of Grignard reagents. Reaction of 2,3-O-isopropylidene-D-ribose (62) with ethynyl magnesium bromide gives l,2-dideoxy-4,5-0-iso-propylidene-D-a//o-hept-l-ynitol (63), which is then converted into its 7-O-trityl ether (64). Treatment of 64 with TsCl/pyridine provides 2,3-0-isopropylidene-5-0-trityl-a-D-ribofuranosylethyne (65) which upon deprotection affords derivative 66 (Scheme 22).89... 

Several observations regarding this aspect have been published, and are briefly mentioned here. 5,6-Dideoxy-6-C-phosphono-D-arabino-hexofuranose (135), an isosteric phosphonate analog of D-arabinose 5-phosphate, is apparently converted, in the presence of enolpyruvate phosphate, into 3,8,9-trideoxy-9-C-phosphono-D-mcmno-2-nonulosonic acid (136) under catalysis by KDO 8-phosphate synthetase from Escherichia coli K 235. Compound 136, an isosteric phosphonate analog of KDO 8-phosphate, is a product inhibitor of the synthetase, and, by the nature of the phosphonate group, is not subject to dephosphorylation as catalyzed by KDO 8-phosphate phosphatase156 (see Scheme 40). Compound 119 (see Scheme 33) is a weak inhibitor of KDO 8-phosphate synthetase.81 KDO inhibits KDO 8-phosphate phosphatase,139 and D-ribose 5-phosphate has an inhibitory... 

Fucosidase inhibiting l,4,5-trideoxy-l,4-imino-L-lyxitol (78) was prepared [124] from D-ribose via protected 5-amino-5-deoxy-L-lyxose (79) by a chemical route. This compound, as well as the 1-aminomethyl homologue (80), obtained by Kiliani-Fischer chain extension of (79), inhibited a-L-fucosidase with K around 2 pmol/1. l,4-Dideoxy-l,4-imino-D-iditol (81) [71] was found to be a moderate inhibitor of the enzyme. 

A base-catalyzed, elimination reaction was a key step in a synthesis of D-ribose from L-glutamic acid.188 In that work, L-glutamic acid was converted, by a series of reactions, into 5-0-benzyl-2,3-dideoxy-D-glycero-pentofuranose (157) from compound 157, a mixture of glycosides was obtained which, on treatment with bromine and calcium carbonate, gave the monobromo derivative 158 as a mixture of diastereoisomers. Base-catalyzed dehydrobromination of 158 afforded the unsaturated derivative 159. Hydroxylation of 159 with potassium permanganate or with osmium tetraoxide gave a mixture of methyl 5-0-benzyl-/3-D-ribofuranoside and methyl 5-O-benzyl-a-D-lyxofuranoside. 

The deamination of derivatives of paromobiosamine [3-0-(2,6-diamino-2,6-dideoxy-/3-L-idopyranosyl)-D-ribose (16)] was used in the elucidation of the structure of the disaccharide, although the interpretation of the results was not straightforward.105 The deamination of the methyl glycoside (17) of this disaccharide106 was first... 

Several deoxy sugars, notably 2-deoxy-D-mY/ o-pentose (2-deoxy-D-ribose) the sugar component of DNA, 6-deoxy-L-mannose (L-rhamnose), 6-deoxy-L-galactose (L-fucose), 6-deoxy-D-glucose (quinovose), and their derivatives, occur very widely in natural products. Also relevant are dideoxy and trideoxy sugars, such as 3,6-dideoxyhexoses, components of the antigenic determinants bacterial... 

Scheme 5.15 Proposed formation of 3-mercapto-2-pentanone and 2-methyl-3-furanthiol from ribose and cysteine via l,4-dideoxy-2,3-diketose2X...

Springer and coworkers874 reported an extensive list of saccharides that were weakly inhibiting or noninhibiting. These included the 2-acetamido-2-deoxy derivatives of D-galactose, D-glucose, D-ribose, D-talose, and D-arabinose, 3,6-dideoxy-L- and -D-xy/o-hexose, L-lyxo-hexosulose, L-arabinose, D-fructose, and 2-deoxy-D-erythro-pentose. 

P. Soro, G. Rassau, P. Spanu, L. Pinna, F. Zanardi, and G. Casiraghi, Total synthesis of 2,4-diamino-2,4-dideoxy-L-arabinose and 2,4-diamino-dideoxy-L- ribose, J. Org. Chem., 61 (1996) 5172-5174. 

When the paromobiosamine fraction is W-benzoylated and then hydrolyzed with dilute acid, D-ribose is one of the products. More-vigorous hydrolysis destroys the D-ribose but yields a diaminodideoxyhexose which was called paromose. A study of the products of periodate oxidation of paromose, of its di-W-acetyl derivative, and of the borohydride reduction product of the latter, revealed that paromose is a 2,6-diamino-2,6-di-deoxyhexose. In a preliminary report, Haskell and Hanessian have presented degradative evidence which establishes the stereochemical structure of paromose as that of 2,6-diamino-2,6-dideoxy-L-idose (7). Their ingenious application of the degradation described by MacDonald and Fischer and by Hough and coworkers of the 1, l-bis(ethanesulfonyl) derivatives of aldoses enabled Haskell and Hanessian to obtain, from iV,fV -diacetylparomose diethyl dithioacetal, a product which they identi-... 

Mild hydrolysis of butirosin A and B with acid slowly liberated n-xylose and n-ribose, respectively. Hydrolysis with concentrated acid gave neamine, neosamine C, 2-deoxystreptamine, and a novel amino acid, 4-amino-3,4-dideoxy-L-gtycero-tetronic acid [(S)-( —)-4-amino-2-hydroxybutyric acid] (53). Treatment of the methyl ester of this amino... 

The synthesis of 3,4-di-0-acetyl-2,6-dideoxy-6,6,6-trifluoro-a-L-/yxo-hexopyra-nosyl bromide from D-lyxose features the use of timethylsilyltrifluoromethane in the presence of fluoride ion to effect the addition of the trifluoromethyl group to an aldehyde. Similar methodology has been utilized in the synthesis of 5-deoxy-5,5,5-trifluoro-D-lyxose, -L-ribose, -L-arabinose and -D-xylose. A symposium report has looked at synthetic routes to 6-deoxy-6,6,6-trifluorosugars and the synthesis of racemic 3-deoxy-2-C-trifluoromethyI-er> //tro and -threo -pentofura-noses is covered in Chapter 14. 

L-Xylose has been converted into a 2-deoxy-2-fluoro-P-L-arabinofuranose derivative, by way of a fluoride ion displacement of an imidazolylsulfonate, and then into a range of pyrimidine nucleosides. Displacement of another imidazolylsulfonate with Et3N.3HF initially formed the corresponding sulfonyl fluoride which was subsequently displaced by fluoride ion. Methyl 2,3-dideoxy-3-fluoro-5-0-(4-methylbenzoyl)-a-D-ribofuranoside, an intermediate for the syntheses of some anti-HIV nucleosides, has been synthesized from 2-deoxy-D-ribose in five steps and in 24% yield. ... 

Diamino-2,4-dideoxy-L-arabinose and -L-ribose, 75 and 76 respectively, were obtained in similar quantities by chain extension of the L-serine-derived aldehyde 74 as shown in Scheme 17. The imino-sugar glycosylamide 78 was... 

In the area of 2, 3 -didehydro-2, 3 -dideoxynucleosides, a new route to compounds of this type in the pyrimidine series is outlined in Scheme 4. The thioglycoside 54 was produced directly from deoxyribose and thiophenol in acidic conditions, and the condensations to form the nucleoside derivatives were P-selective by about 2 l/ A full account has been given of the formation of 2, 3 -didehydro-2, 3 -dideoxy systems from 2, 3 -dimesylates, protected at 0-5, by treatment with telluride anion (see Vol. 27, p. 247)7 Treatment of the furanoid glycal 55, made by cyclization of an acetylenic alcohol (Chapter 13), with silylated thymine in the presence of iodine, followed by sodium methoxide, provides a new route to d4T (56)7 A new synthesis of d4T (56) from 5-methyluridine has also been described, as has a route to d4T labelled with at C-1, which starts from [l- C]-ribose and proceeds via [r- C]-5-methyluridine, convertible in very high yield to [l - C]-d4T. ... 

The six-membered cyclic sugar nitrone 67 was generated in situ from D-ribose derivative 66 and directly trapped with suitable dipolarophiles. Bicyclic isoxazolidines such as 68 were then converted into 1,5-dideoxy-1,5-iminoribitol iminosugar C-glycosides that were tested as glycosidase inhibitors (14JOC4398). 

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