Ribofuranoside synthesis

Purine, 6-bromo-9-/3-D-(2,3,5-tri-0-acetyl)ribofuranosyl-synthesis, 5, 598 Purine, 6-carboxy-reactions, 5, 549 Purine, 8-carboxy-reactions, 5, 549 Purine, 2-chloro-reactions, 5, 561 synthesis, 5, 597 Purine, 6-chloro-alkylation, 5, 529 glycosylation, 5, 529 oxidation, 5, 539 3-oxides reactions, 5, 554 synthesis, 5, 595 reactions, 5, 561, 595 with ammonia, 5, 562 with fluorides, 5, 563 with trimethylamine, 5, 562 9- -D-ribofuranoside synthesis, 5, 560 synthesis, 5, 597, 598 Purine, 8-chloro-amination, 5, 542 Purine, 6-chloro-8-ethoxy-synthesis, 5, 591 Purine, 6-chloro-9-ethyl-dipole moment, 5, 522 Purine, 6-chloro-2-fluoro-riboside... 

VIII. Synthesis of 3-Amino-3-deoxy-D-ribofuranoside Derivatives. A Second Synthesis of 3-Amino-3-deoxy-D-ribose. J. Amer. chem. Soc. 77, 7 (1955). 

Transformation of chiral nitrones into enantiomer enriched a-chiral N -hydroxylamines and their derivatives, has been successfully employed in the enantioselective synthesis of (+ )-(R)- and (—)-(S)-zileuton (216). An expeditious synthesis of thymine polyoxin C (347), based on the stereocontrolled addition of 2-lithiofuran (a masked carboxylate group) to the A-benzyl nitrone derived from methyl 2,3-O-isopropylidene-dialdo-D-ribofuranoside, is described (Scheme 2.151) (194). 

The synthesis of L-ribofuranose derivatives from 16a has been carried out by Walker and Hogenkamp (35). The procedure involves oxidation of the hydroxymethyl group of 16a with dimethyl sulfoxide N,N dicyclohexylcarbodiimide and acid hydrolysis of the protecting group to give L-riburonic acid, which was converted into methyl (methyl a,/ -ribofurano-sid)uronates (26). Reduction of 26 with sodium bis(2-methoxyethoxy)alu-minum hydride gave the chromatographically separable anomers of methyl L-ribofuranoside (27). 

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. 

A very efficient, stereospecific synthesis of DL-ribose was based26 on the use of l,l-diethoxy-5-(tetrahydropyran-2-yloxy)-2-pentyn-3-ol as the substrate. Catalytic hydrogenation of this alkyne to the cts-alkene was accompanied by cyclization, to give 2-ethoxy-2,5-dihydro-5-(tetra-hydropyran-2-yloxy)furan (35). cis-Hydroxylation of the double bond in 35 was effected with potassium permanganate, yielding the ethyl DL-ribofuranoside derivative 36, which was hydrolyzed to DL-ribose. 

Montgomery and Hewson144 have described yet another synthesis for this class of deoxy sugars. Treatment of methyl 2,3-0-isopropylidene-5-0-(p-nitrophenylsulfonyl)-/J-D-ribofuranoside with sodium cyanide in IV,AT-dimethylformamide afforded the corresponding 5-cyano-5-deoxy derivative... 

The de novo discovery synthesis of capecitabine (1) was reported by the Nippon Roche Research Center scientists9,19 and was followed up with a preparation invented by a team at the Hoffinann-La Roche laboratories in New Jersey for the conversion to 1 from 5 -DFCR (10).2° In the first route, 5-fluorocytosine (15) was mono-silated using one equivalent of hexamethyldisilazane in toluene at 100 °C followed by stannic chloride-catalyzed glycosidation with known 5-deoxy-l,2,3-tri-0-acetyl-p-D-ribofuranoside (17) in ice-cooled methylene chloride. While this procedure provided the 2, 3 -di-0-acetyl 5-fluorocytidine 18 in 76% yield on a 25-g scale, an alternative method was also devised using in situ-generated trimethylsilyl iodide in acetonitrile at 0°C to provide a 49% yield of 18 on smaller scale. Acylation of the N -amino group of the bis-protected 5 -DFCR derivative was accomplished by the slow addition of two equivalents of -pentyl chloroformate to a solution of 18 in a mixture of pyridine and methylene chloride at -20 °C, followed by a quench with methanol at room temperature to provide the penultimate intermediate 19 on 800-g scale. The yield of intermediate 19 was assumed to be quantitative and was subjected to the final deprotection step, with only a trituration to... 

Kalckar117118119 has shown that the enzymatic phosphorolysis of inosine (hypoxanthine 9-D-ribofuranoside) may give rise to the formation of a pentose phosphate, isolable as its barium salt. The phosphate was found to be non-reducing although easily hydrolyzed by either acid or alkali to equimolar quantities of phosphate and pentose. In view of these properties and the fact that it could be used for the enzymatic synthesis of purine ribosides, Kalckar has tentatively assigned to it the D-ribose 1-phosphate structure its ring structure and configuration at carbon 1 remain undetermined. 

The backbone of a nucleic acid is a polymer of ribofuranoside rings (five-membered rings of the sugar ribose) linked by phosphate ester groups. Each ribose unit carries a heterocyclic base that provides part of the information needed to specify a particular amino acid in protein synthesis. Figure 23-21 shows the ribose-phosphate backbone of RNA. 

Anderson, Goodman, and Baker employed an O-(methoxycarbonyl) protecting group in an analogous manner for their synthesis of methyl 2,3-anhydro-D-ribofuranoside (XLV). Treatment of 1,2-0-isopropylidene-D-xylofuranose (XLI) with methyl chloroformate in pyridine gave, by preferential esterification of the least-hindered alcohol group (at C5), predominantly 1,2-0-isopropylidene-5-0-(methoxycarbonyl)-D-xylofuranose (XLII) a small proportion of the 3,5-di-0-(methoxycarbonyl) derivative was separated by fractional recrystallization. Subsequently, the C3-hydroxyl was esterified with tosyl chloride, and the resulting 3-0-tosyl ester XLIII... 

Mukaiyama and co-workers revealed that Li salts play a significant role in controlling the novel stereochemical preference that is involved in the glycosidation with ribofur-anose derivatives (Sch. 52). In particular, LiC104 [101-105] and LiNTf2 [105] were found to be effective additives in the stereocontrolled synthesis of a-o-ribofuranosides from 2,3,5-tri-O-benzyl-D-ribofuranose and several alcohols, whereas p anomers were formed in the absence of the lithium salts. Sch. 52 shows several examples that emphasize general characteristics with or without the addition of lithium salts. In the most recently advanced system (Sch. 53), a hypothetical mechanism of this reverse stereocontrol to yield 110 with the influence of lithium salt is also discussed. In the presence of 10 mol % TrC104, both pure a anomer 110 (a /3 = >99 <1) and P anomer 111 a-.p = <1 >99) isomerized to afford a P anomer-rich mixture (a p = 6 94). 

The phosphoramidite derivative of N-nitrothymidine (44) has been synthesised and found suitable for oligonucleotide synthesis using a standard phosphite triester solid phase approach. The N-nitrothymidine residues could be converted into a range of N -modified thymidines by reaction with primary alkyl amines. Phosphoramidite derivatives of 4-nitroindazole N and N -(2 -deoxy-p-D-ribofuranosides) (45, 46) have been synthesised, their base pairing properties investigated and found to show ambiguous base pairing. Seela has also reported the syntheses of the phosphoramidite derivatives of 8-aza-7-adenine... 

Mukaiyama reported an alternative method for the generation of oxophosphonium type intermediates using the reaction of tributylphosphine oxide and triflic anhydride, and applied this reaction to the synthesis of ribofuranosides [415]. 

Mukaiyama proposed an oxotitanium reagent 191 (Figure 4.6) in the presence of triflic anhydride [423] and diphenyltin sulfide with trifiic anhydride [424] for the synthesis of (3-ribofuranosides. The addition of LiC104 to the latter promoter system resulted in the formation of a-ribofuranosides [424]. Mukaiyama and coworkers [344] also reported the use of diphenyltin sulfide with silver salts such as AgC104, or Lawesson s reagent 150 in combination with silver salts. 

Mukaiyama, T, Suda, S, Diphosphonium salts as effective reagents for stereoselective synthesis of 1, 2-cA-ribofuranosides, Chem. Lett., 1143-1146, 1990. 

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