3-benzyl uridine

The first application of this method, for the synthesis of uridine 5 -(a-D-glucopyranosyl pyrophosphate) and uridine 5 -(< -D-galacto-pyranosyl pyrophosphate), involved the use of 2, 3 -di-0-benzyl-uridine 5 -(benzyl phosphorochloridate)316 (70). The desired glycosyl... 

The favored formation of a nucleoside 3 -(alkyl phosphate) was observed on treating the diphenyl phosphate anhydride of uridine 2, 3 -cyclic phosphate with benzyl alcohol.273 In a somewhat related reaction, on treatment with dicyclohexylcarbodiimide in aqueous pyridine, adenosine 2 (3 )-phosphate gave, initially, the 2, 3 -cyclic phosphate, which, on further reaction with the diimide, gave a mixture of the N-phosphonourea nucleoside 44 and its 2 -isomer, in unequal amounts.269 This type of reaction does not seem to occur with... 

Monomolar benzylation of methyl 2,3-di-0-benzyl-a-D-galactopyranoside in DMF gave 2,3,6-tri-O-benzyl derivative in 73% yield [52], The primary 6-benzyl ether also forms the major part of the monobenzyl fraction obtained from methyl a-D-galactopyranoside or from its p-anomer [53]. Interestingly, position 6 becomes less reactive than position 2 if 3,4-0-isopropylidene acetals is used to protect the other two secondary hydroxyl groups. The ratio of 2- and 6-benzyl ethers was found to be 11 1 in the a-anomer and 2.5 1 in the p-anomer [53] (see also, Ref. [54]). Uridine [55], cyti-dine [56], and 4-(methylthio)uridine [56] also prefer OH-2 over the primary position when benzylated in dimethyl sulfoxide (for other benzylations in this solvent, see Refs. [35, 57]). 

Five-membered stannylene derivatives of furanosides exhibit almost no regio-selectivity. A 1 1 mixture of 2 - and 3 -0-benzyl derivatives has been obtained from uridine [128]. Similarly, methyl 5-0-benzoyl-P-D-ribofuranoside gave a 2 3 mixture of 2-benzyl and 3-benzyl ethers in 70 % yield [147], a slightly better result (ratio of 1 3) was obtained-for the parent methyl P-D-ribofuranoside [147a], The reversed ratio (4 1) was found for the a-anomer, methyl 2-0-benzyl-oc-D-ribofuranoside being the major product [147a]. 

A synthetic approach toward tunicamycin 267, based on this principle, has been reported. Tunicamycin shows a direct carbon link between C6 of a galactosamine residue and C5 of a uridine moiety. The formation of this link has been carried out by Wittig reactions on model compounds using Secrist s phosphorane [181]. As shown in Scheme 11.58, the phosphonium salt 263 was treated with lithium hexamethyldisilazane to generate the phosphorane, which was reacted with aldehyde 264. Reduction of the double bond and benzyl hydrogenolysis of 265 was followed by acetylation to provide the model compound 266. 

Reductive desulfurization of the thiocarbonyl group with Raney nickel results in good yields of ethers. 3 -0-Benzyl-2 -deoxy-5-trifluoromethyl-P-uridine (43), claimed as a possible antitumor agent, has been prepared in this way (equation 39). ... 

In a synthesis of coenzyme uridine-diphosphate-glucose (UDPG), Todd and coworkers protected the primary 5-hydroxyl group of uridine (5) by tritylation, benzylated the 2- and 3-hydroxyl groups (6), and removed the trityl group with 80% acetic acid. 

The possibility that, during the alkaline hydrolysis of ribonucleic acid, tri-esters (18) - could be intermediates was ruled out on mechanistic groxmds."f > Furthermore, it was shown that the tri-ester, uridine 2 3 -(methyl phosphate) (18, R = CH3), synthesized by methylation of uridine 2 3 -cychc phosphate with diazomethane, is resistant to ribo-nuclease. f However, it has been observed that, when the benzyl ester of cytidylic acid 6 is partially hydrolyzed in acid, a significant proportion of the o isomer of this phosphoric diester is formed." ) In addition, the dinucleoside phosphates, such as adenylyl-(3 —>5 )-cytidine (14a), are also isomerized to the corresponding (2 - 5 )-dinucleoside phosphates by treatment with acid. " These studies suggest that cyclic triesters (or derivatives thereof) may be intermediates in isomerization of these phospho-diesters in acidic mediiun. 

When 6 -deoxy-5 -iodo-2, 3 -0-isopropylideneuridine (203) is treated with silver dibenzyl phosphate or with silver tribenzyl pyrophosphate, the protected 5 -nucleotide (205, R = benzyl or dibenzyl phosphoric) was obtained after removal of the protecting groups, this gave uridine 5 -phos-phate (206, R = H) and uridine 5 -pyrophosphate (R = POsHa). It is possible that, in the formation of (205) from (203), anhydronucleoside (204) was an intermediate which underwent attack by the phosphoric... 

In a reaction at the benzylic group of 9-phenylxanthen-9-ol, the hydroxyl group was substituted by the uridine moiety with side formation of 4-methoxybenzyl acohol. 

Benzylation of nucleosides. Uridine (1) is converted into N -benzyluridine... 

Bemytation of nucleosides Uridine (1) is converted into N -benzyluridine (2) in quantitative yield when heated with DMF dibenzyl acetal in DMF for 3 hrs. at 80°. This derivative is obtained in only low yield using benzyl bromide and sodium hydride. The blocking group of (2) is removed by sodium naph-thalenide (THF, 3 hr., 84% yield). Guanosine (3) has also been blocked in the same way. 

To a suspension of 77.7 mg 4-amino-l-(3,4-dihydroxy-5-hydroxymethyltetra-hydrofuran-2-yl)-lH-pyrimidin-2-one 3-oxide (cytidine -oxide, 0.30 mmol) and 12.6 mg 95% pure lithium hydride (1.5 mmol) in 5 mL dry methanol was added 40 /xL 98% pure benzyl bromide (0.33 mmol) the mixture was stirred at 37°C for 1 day under an argon atmosphere. TLC analysis of the reaction mixtures with chloroform/methanol/acetic acid (16 6 3) and chloroform/methanol (10 1) as the developing solvents showed complete consumption of the starting material for almost quantitative conversion to a less polar compound. After being neutralized with 1 N HCl solution and subsequent removal of the solvent under reduced pressure, the resulting residue was subjected to a short silica gel column by eluting with chloroform/methanol (20 1) to isolate 99.5 mg l-(3,4-dihydroxy-5-hydroxymethyltetrahydrofuran-2-yl)-17/-pyrimidin-2,4-dione 4- 0-benzyl oxime (uridine 4-0-benzyloxime) as a colorless amorphous powder, in a yield of 95%, m.p. 123-125°C (from methanol). 

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