Unsaturated nucleosides synthesis

Zinc-mediated Barbier-t) e addition of 238, followed by Luche s procedure obtained a mixture of the homoallylic alcohol diastereomers 239 and 240. Alcohol 239 was carried through benzoylation, deketalization, silylation, and ozonolysis, to produce C-branched y-lactone 241. Benzoylation of 240 followed by hydroboration, PCC oxidation, debenzoylation, and alkaline-promoted cyclization directly formed C3-branching 2-deoxyfuranose 242 [87] (O Scheme 63). A novel method for stereoselective synthesis of 4 -a-carbon-substituted nucleosides, through epoxidation of 4, 5 -unsaturated nucleosides and SnCU-promoted epoxy ring opening, was... 

Unsaturated Nucleosides (40) and Their Synthesis from 2-Deoxy-D-err/thro- or -threo-pentofuranosyl Nucleoside Derivatives... 

An illustration of the potential value of 2,3-unsaturated furanoid compounds, particularly in nucleoside synthesis, is the preparation, by way of an epoxy intermediate, of a crystalline compound claimed to be ethyl 3-amino-3-deoxy-DL-arabinofuranoside from racemic 2-eth-oxy-2,5-dihydro-5-(tetrahydropyranyloxymethyl)furan (41, R = OEt,... 

The observation that, under acidic conditions, 2,3-dihydro-4if-pyran will substitute at position 9 of purine derivatives led to the suggestion that nucleosides might be prepared directly from glycals. Although the conditions employed during synthesis of the tetrahydropyranyl derivatives were unsuitable for interaction between 6-chloropurine and 3,4-di-O-acetyl-D-arabinal, when these two compoimds were fused together in the presence of p-toluenesulfonic acid, a mixture of 6-chloro-9-(3,4-di-0-acetyl-2-deoxy-a- and -/3-D-er2/iAro-pentopyranosyl)purines resulted, from which the known a-D anomer was isolated in pure form. Alternatively, an unsaturated nucleoside was obtained from tri-O-acetyl-D-glucal by this method (see p. 91). 

Synthesis of showdomycin (4) by carbon-carbon bond formation between the D-ribose and maleimide subunits usually lacks stereospecificity and affords a mixture of 4 and its a anomer 94. Thus, reaction of unprotected D-ribose (90) with the maleimide-derived Wittig reagent 91 gave the unsaturated nucleoside 92 that was cyclized by the introduction and removal of a phenylseleno group to give a mixture of 4 and 94 the latter preponderated (84JOC3673 86JOC495) (Scheme 16). 

Three additional approaches to the synthesis of CNT are shown in Fig. 9. The first [77, 78] involves transformation of 3 -ketonucleoside 44 into cyanohydrin 45, followed by deoxygenation at 3 and then at 2 to afford 47, which is easily epimerized to 31 by treatment with base (pH = 9). Treatment of 2 -0-acyl derivatives of 46 with bases produced elimination to give the 2, 3 -unsaturated nucleoside 48. An important factor in the chemistry of these cyanonucleosides is the acidity of the H-3 hydrogen atom in a-position to the nitrile group. This acidity is responsible for the facile epimerization 47 31 and for the elimination... 

A short route for the synthesis of a 2, 3 -unsaturated nucleoside from a 2, 3 -0-cyclic derivative involves transformation of uridine into 2, 3 -0-methoxy-methylideneuridine (90) which, after elimination by heating in acetic anhydride and deacetylation, affords 78f in 41 % yield from uridine [132]. This method was not successful when applied to the synthesis of 78a and 78b [132]. 

Several papers describe the synthesis of azido-sugar precursors to amino-sugar nucleosides. The unsaturated nucleosides (34) were converted to the corresponding amino-compounds (35) by sequential treatment with triphenyl-phosphine-tetrabromomethane and lithium azide followed by reduction, the product amines then being coupled to amino-acids to give amino-acyl derivatives, which showed slight antitumour activity. " A facile new synthesis of 2 -amino-2 -... 

The reaction of cyclic thiocarbonates with methyl iodide (Chapter 13) and the use of 5 -deoxy-5 -iodo-nucleosides in the synthesis of unsaturated nucleosides (Chapter 14) are reported elsewhere. 

The synthesis of unsaturated nucleosides falls into two groups first, where an unsaturated sugar is condensed with a base second, where unsaturation is introduced into an existing nucleoside. Thus, the unsaturated hexofuranosyl derivative (380) was coupled to 6-benzamidochloromercuripurine by the titanium chloride method to give the adenine derivative (381). In a somewhat different... 

Scheme 2 outlines the synthesis of the glycosulose nucleoside derivative, 4 -methoxyadenosine (31), involving stereospecific addition of methoxy-iodine to a 4, 5 -unsaturated nucleoside intermediate other 5-substituted analogues of (31) were prepared by standard displacements on the 5 -iodo-precursor. ... 

S. Phadtare, D. Kessel, and J. Zemlicka, Unsaturated nucleoside analogues Synthesis... 

The use of nitro-olefins as starting materials for conversion into nitro-qxixides is mentioned in Ch ter 10. The preparation of 2,3-unsaturated nucleosides is covered in Chapter 20 and the synthesis of derivatives of 3-hydroxy-2(SH)-furanose (isotetronic acid) from boizylidene acetal... 

Dideoxynucleosides and 2, 3 -unsaturated nucleoside analogs are of interest as potential chain terminators of DNA biosynthesis. 2, 3 -Dldeoxycytidlne and the corresponding 2, 3 -unsaturated nucleoside were synthesized via an "epoxy" nucleoside intermediate. The synthesis of 2, 3 -dehydro-5-fluoro-2 -deojqruridine (DHFUDR, XIII) was achieved by... 

D-Ribonolactone is a convenient source of chiral cyclopentenones, acyclic structures, and oxacyclic systems, useful intermediates for the synthesis of biologically important molecules. Cyclopentenones derived from ribono-lactone have been employed for the synthesis of prostanoids and carbocyclic nucleosides. The cyclopentenone 280 was synthesized (265) from 2,3-0-cyclohexylidene-D-ribono-1,4-lactone (16b) by a threestep synthesis that involves successive periodate oxidation, glycosylation of the lactol with 2-propanol to give 279, and treatment of 279 with lithium dimethyl methyl-phosphonate. The enantiomer of 280 was prepared from D-mannose by converting it to the corresponding lactone, which was selectively protected at HO-2, HO-3 by acetalization. Likewise, the isopropylidene derivative 282 was obtained (266) via the intermediate unsaturated lactone 281, prepared from 16a. Reduction of 281 with di-tert-butoxy lithium aluminum hydride, followed by mesylation, gave 282. 

This Subsection deals with the preparation of 2 - and 4 -ketohexosyl-purines and -pyrimidines, which have proved to be versatile synthetic intermediates. A 5 -keto derivative of a hexofuranose nucleoside is also described. The synthesis of epoxy-, halogeno-, unsaturated, epimino-, and thio-ketonucleosides will be developed in subsequent Subsections and Sections. 

Among the unsaturated ketonucleosides may be classified the disaccharide derivative 74, which is an analog of the biologically active compound 68c. The key intermediate for the synthesis of this unsaturated ketodisaccharide nucleoside was the partially protected, disaccharide nucleoside 73, which was prepared by two separate routes,56 Treatment of 73 with the Me2SO-acetic anhydride reagent for two days at room temperature afforded 7-[2,3-di-0-benzoyl-4-0-(3-0-benzoyl-2,6-di-deoxy - / - d - glycero - hex - 2 - enopyranosyl - 4 - ulose) - 6 - deoxy - / - d -glycopyranosyl]theophylline (74), isolated crystalline.56... 

Sugar derivatives that contain double bonds have been developed and used so extensively that they almost certainly constitute the most versatile category of carbohydrate compounds available for use in synthesis. They may be applied both in the synthesis of complex members of the family and of a myriad enantiomerically pure noncarbohydrate compounds—notably, many of interest in medicinal chemistry. Furthermore, some unsaturated sugar derivatives have themselves been found to possess important therapeutic properties. For example, the unnatural L-nucleoside 1 inhibits reverse transcriptase and shows potent and selective anti-AIDS activity,1 and the unsaturated neuraminic acid analogue 2 is the sialidase-inhibitory... 

B. Dobazewski, N. Blaton, and P. Herdewijn, Synthesis of / -configured 2, 3 -unsaturated pentopyranosyl nucleosides, Tetrahedron Lett., 36 (1995) 1321-1324. 

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