Ribofuranosyl bromide

In the case of indazoles the reaction of indazole, 5-nitroindazole or 6-nitroindazole with glycosyl halides and mercury(n) cyanide gives exclusively 2-glycosylindazoles (670), (673) and (675) (7QJHC1435). Similarly, the reaction of 1-trimethylsilyl derivatives of indazole, 3-cyanoindazole, 4-nitroindazole, 5-nitroindazole and 6-nitroindazole with 2,3,5-tri-O-acetyl-D-ribofuranosyl bromide gives only, or preferentially, the 2-ribofuranosyl derivatives (670)-(674) 7QJHC117, 70JHC1329). 

Derivatives of 3-oxo-l,2,4-triazine 1-oxide undergo alkylation with various alkylating agents. Thus the reaction of 3-methoxy-l,2,4-triazine 1-oxide 20 with 2,3,5-tii-(9-benzoyl-/3-D-ribofuranosyl bromide, followed by the removal of the benzoyl protection with sodium methoxide, leads to an abnormal nucleoside 4-(/3-D-iibofuranosyl)-l,2,4-triazin-3(4//)-one 1-oxide 21 (73JOC3277). 

These acid-catalyzed C-glycosylations were successfully extended to the D-ribofuranose series by Sorm and coworkers,148 who utilized the reaction in the first reported synthesis of showdomycin. Thus, treatment of 2,3,5-tri-0-benzoyl-/3-D-ribofuranosyl bromide (81) with 1,2,5-trimethoxybenzene in the presence of zinc oxide gave 2,4,6-trimethoxy-l-(2,3,5-tri-0-benzoyl-/3-D-ribofuranosyl)benzene (196). Ozonolysis of the corresponding acetate derivative, followed by esterification, gave the highly functionalized C-/3-I>ribofuranosyl derivative (197), which was used as a key intermediate in the synthesis of showdomycin (see Section III,l,b). 

Glycosylation of 3-amino-5(7)//-[l,2,4]triazolo[4,3-3] l,2,4 triazole 17 with 1-O-acetyl- 2,3,5-tri-O-benzoyl-D-ribo-furanose 18 or 2,3,5-tri-O-benzoyl-D-ribofuranosyl bromide 19 can be selective or nonselective, depending on the reaction conditions (Scheme 1). In the presence of trimethylsilyl triflate or boron trifluoride etherate, the... 

Fletcher and coworkers have utilized the poly-O-acylaldofuranosyl halides. Treatment of crude tri-O-benzoyl-D-ribofuranosyl bromide with sodium phenoxide in 1,2-dimethoxyethane gave phenyl /9-D-ribo-furanoside88 use of sodium methoxide gave methyl /9-D-ribofuranoside.88... 

Aside from the successful synthesis of cytidine,185 attempts made thus far to apply the Hilbert reaction to the preparation of 1 -glycofuranosyl-pyrimidines have yielded anomalous results. Although the syntheses of 5 -methyluridine (I, R = CH3) and 5 -methylcytidine (II, R = CH3) by the condensation of sirupy tri-O-acetyl-D-ribofuranosyl bromide with 2,4-diethoxypyrimidine have been reported,192 the properties of these nucleosides differ from those of the verified substances synthesized by other routes.68 62 Other aspects of the Hilbert-Johnson procedure are discussed below. 

Progress toward the synthesis of cozymase has been made by Haynes and Todd.154 Nicotinamide and triacetyl-D-ribofuranosyl bromide were... 

Alkylation of the oxadiazolo[3,4-c][l,2,6]thiadiazine 5,5-dioxide (41 R1 = H) using 2,3,5-tri-O-benzoyl-D-ribofuranosyl bromide and mercuric cyanide is reported to give the 3-ribofuranosyl derivative (42 R = PhCO)(12%) as the minor product in addition to the 4-substituted derivative (41 R1 = 2,3,5-tri-0-benzoyl-/ -D-ribofuranosyl) (64%) (see Section 7.14.6.1) <82JHC305>. 

N-Alkylation in the azine ring is demonstrated by the preparation of 2-substituted 6-(jS-D-ribofuranosyl)oxazolo[5,4-rf]pyrimidin-7(6/T)-ones (181). In this case the silyl ether variant of the Hilbert-Johnson method for the synthesis of pyrimidine nucleosides has been used the pyrimidinone (180) is converted into its silyl ether using HMDS and the ether reacted with 2,3,5-tri-O-acetyl-D-ribofuranosyl bromide under Hg(II) catalysis. Deacetylation using methanolic ammonia gives the nucleoside with a /3-anomeric configuration (74JMC1282). 

Ribofuranosylamine, N - (o - carboxy-phenyl)-/3-D-, 5-phosphate, 265 Ribofuranosyl bromide, 5-0-benzoyl-n-,... 

Direct condensation of 2,3,5-tri-0-benzoyI-/3-D-ribofuranosyl bromide with adenine in acetonitrile at 50 °C leads after deblocking to the 3-/3-D-ribofuranosyladenine (132) (B-68MI40901). Metal derivatives of purines tend to produce 7- or 9-glycosyl derivatives thus the silver salt of 2,8-dichloroadenine with 2,3,5-tri-O-acetylribofuranosyl chloride produces the 9-/3-D-ribofuranosyl derivative (133) (48JCS967, 48JCS1685). However similar reactions with theobromine produce O-glycosides and with theophylline N-7 derivatives (34JCS1639). 

In a similar manner purine nucleotides including AMP and its a-anomer may be produced directly by reaction of the iV -benzoyl-9-bis(trimethylsilyl)adenine with 2,3-di-O-benzoyl-5-0-(diphenylphosphono)-D-ribofuranosyl bromide and deblocking the intermediate with lithium hydroxide and a phosphodiesterase from Trimeresums flavoviridis (b-78MI40903, p, 82l). This method however gives a low yield and can hardly be recommended. 

Nucleosides such as (246) have been prepared by the coupling of the trimethylsilyl derivative of (244) with 2,3,5-tri-0-acetyl-j8-D-ribofuranosyl bromide (245) followed by deacetylation (75JOC3708). Arabinose derivatives substituted at N-1 have also been prepared (76JMC814). 

The adenosine analog containing an imidazo[4,5-c]pyridazine (252) has been prepared by the condensation of (249) with 2,3,5-tri-O-benzoyl-D-ribofuranosyl bromide (250) to produce (251). Removal of the benzoyl groups is readily achieved by methanolic ammonia at room temperature, and then the chlorine is displaced with ethanolic ammonia in an autoclave at high temperatures to afford (252) (74JHC39). 

Finally, mention must be made of the nicotinamide nucleosides. Fischer and Raske observed the quaternization of tetra-O-acetyl-a-D-glucopyranosyl bromide with pyridine, and Karrer and coworkers extended this reaction to the synthesis of quaternary, nicotinamide nucleosides. The condensation has been improved by Haynes and Todd, who used acetonitrile as solvent. With tri-O-acetyl-a-D-ribofuranosyl bromide, D-ribofuranosylnicotinamide—a structural unit of coenzyme I (DPN)—was obtained, and this was reduced with sodium dithionite to the dihydro derivative. 

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