Synthesis of 1-(2,3-Dideoxy-β-d-glycero-pent-2-enofuranosyl)thymine (d4T; Stavudine) from 5-Methyluridine

Abstract

A practical synthetic method of d4T (3) from 5-methyluridine (2a) was developed. The Marumoto-Mansuri method was modified using 2′,3′-O-methoxy-ethylidene-5-methyluridine (10) as an intermediate to afford 1-(3,5-di-O-acetyl-2-bromo-2-deoxy-β-D-ribofuranosyl)thymine (6a) in high yield with less formation of by-products. The reaction mechanism was also discussed.

     

Enzymatic regioselective and complete deacetylation of two arabinonucleosides

Candida antarctica lipase B (CAL-B)-catalysed regioselective deacetylation of 2′,3′,5′-tri-O-acetyl-1-β-d-arabinofuranosyluracil (1) and 2′,3′,5′-tri-O-acetyl-9-β-d-arabinofuranosyladenine (2) was studied. The choice of the reaction medium allowed the regioselective formation of products bearing different degree of acetylation: in isopropanol, CAL-B catalysed the formation of the corresponding 2′-O-acetylated arabinonucleosides, while hydrolyses afforded the 2′,3′-di-O-acetylated products. In particular, the procedure herein described allows a simple and efficient preparation of the reported vidarabine prodrug 2′,3′-di-O-acetyl-9-β-d-arabinofuranosyladenine, avoiding the utilisation of protective groups. Moreover, to achieve full deacetylation of the assayed substrates, a set of commercial hydrolases and fungal keratinases from Doratomyces microsporus (DMK) and Paecilomyces marquandii (PMK) were tested. While only PMK and DMK catalysed the quantitative complete deacetylation of 1, DMK accomplished full deacetylation of 2 in shorter time than the other assayed enzymes.     

Regioselective acylation of several polyhydroxylated natural compounds by Candida antarctica lipase B

Regioselective acylation of four polyhydroxylated natural compounds, deacetyl asperulosidic acid (1), asperulosidic acid (2), puerarin (3) and resveratrol (4) by Candida antarctica Lipase B in the presence of various acyl donors (vinyl acetate, vinyl decanoate or vinyl cinnamoate) was studied. Compounds 1, 2 and 4 were regioselectively acetylated with vinyl acetate to afford products, 3′-O-acetyl-10-O-deacetylasperulosidic acid (1a), 3′,6′-O-diacetyl-10-O-deacetylasperulosidic acid (1b), 3′-O-acetylasperulosidic acid (2a), 3′,6′-O-diacetylasperulosidic acid (2b), 4′-O-acetylresveratrol (4a), respectively, with yields of 22 to 50%, while reactions with vinyl decanoate and vinyl cinnamoate were slow with lower yields. Compound 3 was readily acylated with all three acyl donors and quantitatively converted to products 6″-O-acetylpuerarin (3a), 6″-O-decanoylpuerarin (3b), 6″-O-cinnamoylpuerarin (3c), respectively. The structures of these acylated products were determined by spectroscopic methods (MS and NMR).     

SYNTHESIS of 2′-DEOXY-2′-FLUOROGUANYL-(3′,5′)-GUANOSINE

ABSTRACT

The protected analogue of 2-amnio-6-chloropurine arabinoside (3b) was subjected to reaction with diethylaminosulfur trifluoride (DAST) and subsequently treated with NaOAc in Ac₂O/AcOH to give N ²,O ^3′,O ^5′-triacetyl-2′-deoxy-2′-fluoroguanosine (5a). After deacetylation of the sugar moiety and protection of 5′-OH by a 4,4′-dimethoxytrityl group, this nucleoside component was converted to 2′-deoxy-2′-fluoroguanyl-(3′,5′)-guanosine (6c, GfpG).     

Nucleosides and Nucleotides. 104. Radical and Palladium-Catalyzed Deoxygenation of the Allylic Alcohol Systems in the Sugar Moiety of Pyrimidine Nucleosides§,1

Abstract

New methods for the synthesis of 2′,3′-didehydro-2′,3′-dideoxy-2′ (and 3′)-methyl-5-methyluridines and 2′,3′-dideoxy-2′ (and 3′)-methylidene pyrimidine nucleosides have been developed from the corresponding 2′ (and 3′)-deoxy-2′ (and 3′)-methylidene pyrimidine nucleosides. Treatment of a 3′-deoxy-3′-methylidene-5-methyluridine derivative 8 with 1,1′-thiocarbonyldiimidazole gave the allylic rearranged 2′,3′-didehydro-2′,3′-dideoxy-3′-[(imidazol-1-yl)carbonylthiomethyl] derivative 24. On the other hand, reaction of 8 with methyloxalyl chloride afforded 2′-O-methyloxalyl ester 25. Radical deoxygenation of both 24 and 25 gave 26 exclusively. Palladium-catalyzed reduction of 2′,5′-di-O-acetyl-3′-deoxy-3′-methylidene-5-methyluridine (32) with triethylammonium formate as a hydride donor regioselectively afforded the 2′,3′-dideoxy-3′-methylidene derivative 35 and 2′,3′-didehydro-2′,3′-dideoxy-3′-methyl derivative 34 in a ratio of 95:5 in 78% yield. These reactions were used on the corresponding 2′-deoxy-2′-methylidene derivatives. An alternative synthesis of 2′,3′-dideoxy-2′-methylidene pyrimidine nucleosides (43, 52, and 54) was achieved from the corresponding 1-(3-deoxy-β-D-thero-pentofuranosyl)pyrimidines (44 and 45). The cytotoxicity against L1210 and KB cells and inhibitory activity of the pathogenicity of HIV-1 are also described     

Synthesis and bioactivity of 5-(1-aryl-1H-tetrazol-5-ylsulfanylmethyl)-N-xylopyranosyl-1,3,4-oxa(thia)diazol-2-amines

A series of new N′-[N-(2,3,4-tri-O-acetyl-β-d-xylopyranosyl)thiocarbamoyl]-2-[(1-aryl-1H-tetrazol-5-yl)sulfanyl]acetohydrazides 5a–5e were synthesized rapidly in high yields from 2-(1-aryl-1H-tetrazol-5-ylsulfanyl)acetohydrazides 3a–3e and 2,3,4-tri-O-acetyl-β-d-xylopyranosyl isothiocyanate 4, then 5a–5e were converted to a series of new 5-(1-aryl-1H-tetrazol-5-ylsulfanylmethyl)-N-(2,3,4-tri-O-acetyl-β-d-xylopyranosyl)-1,3,4-oxadiazole-2-amines 6a–6e and 5-(1-aryl-1H-tetrazol-5-ylsulfanylmethyl)-N-(2,3,4-tri-O-acetyl-β-d-xylopyranosyl)-1,3,4-thiadiazole-2-amines 7a–7e, respectively under mercuric acetate/alcohol system or acetic anhydride/phosphoric acid system, then deacetylated in the solution of CH₃ONa/CH₃OH. All of the novel compounds were characterized by IR, ¹H NMR, ¹³C NMR, MS and elemental analysis. The structures of compounds 2e, 3e, 5a and 5c have been determined by X-ray diffraction analysis. Some of the synthesized compounds displayed PTP1B inhibition and microorganism inhibition.     

Synthesis of C-glycopyranosylfuran derivatives by reaction of dialdehydes with cyanoacetamide

The reaction of diglycol- and thiodiglycol-aldehyde (1a,b) with cyanoacetamide yields cis-3,5-diacetoxy-4-carbamoyl-4-cyano-tetrahydropyran (2a) and -tetrahydrothiopyran (2b). When this reaction is applied to (2S)-2-(3-ethoxycarbonyl-2-methyl-5-furyl)-3,5-dihydroxy-1,4-dioxane (1c), (2S)-3,5-dihydroxy-2-(3-methoxycarbonyl-2-methyl-5-furyl)-1,4-dioxane (1d), and (2S,3R,5S)-2-(3-acetyl-2-methyl-5-furyl)-3,5-dihydroxy-1,4-dioxane (1e), 5-(3-carbamoyl-3-cyano-3-deoxy-β-d-xylo-pentopyranosyl)-3-ethoxycarbonyl-2-methylfuran (2c), 5-(2,4-di-O-acetyl-3-carbamoyl-3-cyano-3-deoxy-β-d-xylo-pentopyranosyl)-3-methoxycarbonyl-2-methylfuran (2e), and 3-acetyl-5-(2,4-di-O-acetyl-3-carbamoyl-3-cyano-3-deoxy-β-d-xylo-pentopyranosyl)-2-methylfuran (2f), respectively, are formed with (4S,5S)-4-carbamoyl-4-cyano-2-(3-ethoxycarbonyl-2-methyl-5-furyl)-5-hydroxy-5,6-dihydropyran (3a) and (4S,5S)-4-carbamoyl-4-cyano-5-hydroxy-2-(3-methoxycarbonyl-2-methyl-5-furyl)-5,6-dihydropyran (3b) as minor products. The dehydration of 2a,b, 5-(2,4-di-O-acetyl-3-carbamoyl-3-cyano-3-deoxy-β-d-xylo-pentopyranosyl)-3-ethoxycarbonyl-2-methylfuran (2d), 2e, and 2f yields cis-3,5-diacetoxy-4,4-dicyano-tetrahydropyran and -tetrahydrothiopyran (2l,m), and the 5-(2,4-di-O-acetyl-3,3-dicyano-3-deoxy-β-d-erythro-pentopyranosyl) derivatives (2n–p) of 3-ethoxycarbonyl-2-methylfuran, 3-methoxycarbonyl-2-methylfuran, and 3-acetyl-2-methylfuran, respectively.     

Novel 2′-Deoxy Pyrazine C-Nucleosides Synthesized VIA Palladium-Catalyzed Cross-Couplings

Abstract

The palladium-catalyzed cross-couplings of 2-chloro-3,5-diamino-6-iodopyrazine (1a) and methyl 3-amino-6-iodopyrazine-2-carboxylate (1b) with 1,4-anhydro-3,5-O-bis[(tert-butyl)dimethylsilyl]-2-deoxy-D-erythro-pent-1-enitol (2) followed by desilylation and stereospecific reduction of the 2′-deoxy-3′-keto adduct leads to the formation of 2-chloro-6-(2-deoxy-ß-D-ribofuranosyl)-3,5-diaminopyrazine (4a) and methyl 3-amino-6-(2-deoxy-ß-D-ribofuranosyl)pyrazine-2-carboxylate (4b) in 58% yield and 21% yield, respectively. These are the first syntheses of the heretofore unknown 2′-deoxy pyrazine C-nucleosides and demonstrate the utility of a convergent approach for the synthesis of pyrazine C-nucleosides.     

Keto-fluorothiopyranosyl nucleosides: a convenient synthesis of 2- and 4-keto-3-fluoro-5-thioxylopyranosyl thymine analogs

A novel series of fluorinated keto-β-d-5-thioxylopyranonucleosides bearing thymine as the heterocyclic base have been designed and synthesized. Deprotection of 3-deoxy-3-fluoro-5-S-acetyl-5-thio-d-xylofuranose (1) and selective acetalation gave the desired isopropylidene 5-thioxylopyranose precursor 3. Acetylation and isopropylidene removal followed by benzoylation led to 3-deoxy-3-fluoro-1,2-di-Ο-benzoyl-4-O-acetyl-5′-thio-d-xylopyranose (6). This was condensed with silylated thymine and selectively deacetylated to afford 1-(2′-Ο-benzoyl-3′-deoxy-3′-fluoro-5′-thio-β-d-xylopyranosyl)thymine (8). Oxidation of the free hydroxyl group in the 4′-position of the sugar led to the formation of the target 4′-keto compound together with the concomitant displacement of the benzoyl group by an acetyl affording, 1-(2′-O-acetyl-3′-deoxy-3′-fluoro-β-d-xylopyranosyl-4′-ulose)thymine (9). Benzoylation of 3 and removal of the isopropylidene group followed by acetylation, furnished 3-deoxy-3-fluoro-1,2-di-Ο-acetyl-4-O-benzoyl-5′-thio-d-xylopyranose (12). Condensation of thiosugar 12 with silylated thymine followed by selective deacetylation led to the 1-(4′-Ο-benzoyl-3′-fluoro-5′-thio-β-d-xylopyranosyl)thymine (14). Oxidation of the free hydroxyl group in the 2′-position and concomitant displacement of the benzoyl group by an acetyl gave target 1-(4′-O-acetyl-3′-deoxy-3′-fluoro-β-d-xylopyranosyl-2′-ulose)thymine (15).     

Photo-oxygenation of polyhydroxyalkylfurans: rearrangement of O-acetyl derivatives

The photo-oxygenation of ethyl 2-methyl-5-(1,2,3,4-tetra-O-acetyl-d-lyxo-tetritol-1-yl)-3-furoate, ethyl 2-methyl-5-(1,2,3,4-tetra-O-acetyl-d-arabino-tetritol-1-yl)-3-furoate, 3-acetyl-2-methyl-5-(1,2,3,4-tetra-O-acetyl-d-arabino-tetritol-1-yl)furan, and ethyl 5-(1,4-di-O-acetyl-2,3-O-isopropylidene-d-lyxo-tetritol-1-yl)-2-methyl-3-furoate yielded the corresponding 1,4-endo-peroxides (3a–3d as pairs of diastereomers). Each diastereomer of the pairs 3a and 3d was isolated by fractional crystallisation. The rearrangement of the endo-peroxides at room temperature, by dissolution in CDCl₃, yielded the corresponding diepoxides and monoepoxides. The reduction of 3a–3d with methyl sulphide yielded the corresponding γ-diketones, ethyl (E)-2-C-acetyl-5,6,7,8-tetra-O-acetyl-2,3-dideoxy-d-lyxo-oct-2-en-4-ulosonate, ethyl (E)-2-C-acetyl-5,6,7,8-tetra-O-acetyl-2,3-dideoxy-d-arabino-oct-2-en-4-ulosonate, 3-C-acetyl-6,7,8,9-tetra-O-acetyl-1,3,4-trideoxy-d-arabino-non-3-eno-2,5-diulose, and ethyl (E)-2-C-acetyl-5,8-di-O-acetyl-2,3-dideoxy-6,7-O-isopropylidene-d-lyxo-oct-2-en-4-ulosonate, which can isomerise into the corresponding Z isomers.     

Synthesis of 5,6-dideoxy-3-O-methyl-5-C-(phenylphosphinyl)-d-glucopyranose and its 1,2,4-triacetate

Methyl phenylphosphonite or dimethyl phosphite underwent acid-catalyzed addition reactions with some hexofuranos-5-ulose 5-(p-tolylsulfonylhydrazones) (7, 9, and 16), to give the corresponding adducts, 17, 18, 19, and 21. The isomer ratios of the adducts were affected by a 3-substituent in the hydrazones. Treatment of adduct 21 with sodium borohydride and sodium dihydrobis(2-methoxyethoxy)-aluminate (SDMA), followed by acid hydrolysis, gave 5,6-dideoxy-3-O-methyl-5-C-(phenylphosphinyl)-d-glucopyranose (26), which was acetylated to give the 1,2,4-tri-O-acetyl derivatives 27a and 27b. Conformational analysis of compound 27a by X-ray crystallography revealed that the compound was 1,2,4-tri-O-acetyl-5,6-dideoxy-3-O-methyl-5-C-[(S)-phenylphosphinyl]-β-d-glucopyranose in the ⁴C₁(d) form having all substituents equatorial.     

Synthesis of Certain 4-Substituted-1-β-D-Ribofuranosyl-3-Hydroxypyrazoles Structurally Related to the Antibiotic Pyrazofurin

Abstract

Several 4-substituted-1-β-D-ribofuranosyl-3-hydroxypyrazoles were prepared as structural analogs of pyrazofurin. Glycosylation of the TMS derivative of ethyl 3(5)-hydroxypyrazole-4-carboxylate (3) with 1-0-acetyl-2,3,5-tri-0-benzoyl-D-ribofuranose in the presence of TMS-triflate gave predominantly ethyl 3-hydroxy-1-(2,3,5-tri-0-benzoyl-β-D-ribofuranosyl)pyrazole-4-carboxylate (4a), which on subsequent ammonolysis furnished 3-hydroxy-1-β-D-ribofuranosylpyrazole-4-carboxamide (5). Benzylation of 4a with benzyl bromide and further ammonolysis gave 3-benzyloxy-1-β-D-ribofuranosylpyrazole-4-carboxamide (8a). Catalytic (Pd/C) hydrogenation of 8a afforded yet another high yield route to 5. Saponification of the ester function of ethyl 3-benzyloxy-1-β-D-ribofuranosylpyrazole-4-carboxylate (7b) gave the corresponding 4-carboxylic acid (6a). Phosphorylation of 8a and subsequent debenzylation of the intermediate 11a gave 3-hydroxy-1-β-D-ribofuranosylpyrazole-4-carboxamide 5′-phosphate (11b). Dehydration of 3-benzyloxy-1-(2,3,5-tri-0-acetyl-β-D-ribofuranosyl)pyrazole-4-carboxamide (8b) with POCl₃ provided the corresponding 4-carbonitrile derivative (10a), which on debenzylation with Cl₃SiI gave 3-hydroxy-1-(2,3,5-tri-0-acetyl-β-D-ribofuranosyl)pyrazole-4-carbonitrile (13). Reaction of 13 with H₂S/pyridine and subsequent deacetylation gave 3-hydroxy-1-β-D-ribofuranosylpyrazole-4-thiocarboxamide (12b). Similarly, treatment of 13 with NH₂OH afforded 3-hydroxy-1-β-D-ribofuranosylpyrazole-4-carboxamidoxime (14a), which on catalytic (Pd/C) hydrogenation gave the corresponding 4-carboxamidine derivative (14b). The structural assignment of these pyrazole ribonucleosides was made by single-crystal X-ray analysis of 6a. None of these compounds exhibited any significant antitumor or antiviral activity in cell culture.     

Synthesis of Methylene-Bridged Analogues of Nicotinamide Riboside,Nicotinamide Mononucleotide and Nicotinamide Adenine Dinucleotide

Abstract

5-O-tert-Butyldimethylsilyl-1,2-O-isopropylidene-3(R)-(nicotinamid-2-ylmethyl)-α-D-ribofuranose (11a) and ?3(R)-(nicotinamid-6-ylmethyl)-α-D-ribofuranose (11b) were prepared by condensation of 5-O-tert-butyldimethylsilyl-1,2-O-isopropylidene-α-D-erythro-3-pentulofuranose (10) with lithiated (LDA) 2-methylnicotinamide and 6-methylnicotinamide, respectively, and then deprotected to give 1,2-O-isopropylidene-3-(R)-(nicotinamid-2-ylmethyl)-α-D-ribofuranose(12a) and 1,2-O-isopropylidene-3(R)-(nicotinamid-6-ylmethyl)-α-D-ribofuranose (12b). Benzoylation as well as phosphorylation of compounds 12 afforded the corresponding 5-O-benzoate (13b) and 5-O-monophosphates (14a and 14b). Treatment of 13b with CF₃COOH/H₂O caused 1,2-de-O-isopropylidenation with simultaneous cyclization to the corresponding methylene-bridged cyclic nucleoside - 3′,6-methylene-1-(5-O-benzoyl-β-D-ribofuranose)-3-carboxamidopyridinium trifluoro-acetate (8b) - restricted to the “anti” conformation. In a similar manner compounds 14a and 14b were converted into conformationally restricted 2,3′-methylene-1-(β-D-ribofuranose)-3-carboxamidopyridinium-5′-monophosphate (9a - “syn”) and 3′,6-methylene-1-(β-D-ribofuranose)-3-carboxamido -pyridinium-5′monophosphate (9b - “anti”) respectively. Coupling of derivatives 12a and 12b with the adenosine 5′-methylenediphosphonate (16) afforded the corresponding dinucleotides 17. Upon acidic 1,2-de-O-isopropylidenation of 17b, the conformationally restricted P¹-[6,3′-methylene-1-(β-D-ribofuranos-5-yl)-3-carboxamidopyridinium]-P²-(adenosin-5′-yl)methylenediphosphonate 18b -“anti” was formed. Compound 18b was found to be unstable. Upon addition of water 18b was converted into the anomeric mixture of acyclic dinucleotides, i. e. P¹-[3(R)-nicotinamid-6-ylmethyl-D-ribofuranos-5-yl]-P²-(adenosin-5′-yl)-methylenediphosphonate (19b). In a similar manner, treatment of 17a with CF₃COOH/H₂O and HPLC purification afforded the corresponding dinucleotide 19a.

     

Highly selective biotransformation of (+)-(1S)- and (−)-(1R)-camphorquinone by Aspergillus wentii

Abstract

To clarify the structures of biotransformation products and metabolic pathways, the biotransformation of monoterpenoids, (+)- and (?)-camphorquinone (1a and b), has been investigated using Aspergillus wentii as a biocatalyst. Compound 1a was converted to (?)-(2S)-exo-hydroxycamphor (2a), (?)-(2S)-endo-hydroxycamphor (3a), (?)-(3S)-exo-hydroxycamphor (4a), (?)-(3S)-endo-hydroxycamphor (5a), and (+)-camphoric acid (6a). Compound 1b was converted to (+)-(2R)-exo-hydroxycamphor (2b), (+)-(2R)-endo-hydroxycamphor (3b), (+)-(3R)-exo-hydroxycamphor (4b), (+)-(3R)-endo-hydroxycamphor (5b), and (?)-camphoric acid (6b). Compound 1a mainly produced 2a (65.0%) with stereoselectivity, whereas 1b afforded 3b (84.3%) with high stereoselectivity. These structures were confirmed by gas chromatography–mass spectrometry, infrared, ¹H nuclear magnetic resonance (NMR), and ¹³C NMR spectral data. The products illustrate the marked ability of A. wentii for enzymatic oxidation and ketone reduction.     

Synthesis and Biologic Evaluation of 8-Substituted Derivatives of Nebularine (9-β-D-Ribofuranosylpurine)

Abstract

A series of 8-substituted purine ribonucleosides were prepared from 2′, 3′, 5′-tri-O-acetyl-8-bromoadenosine and evaluated for cytotoxicity and antiviral activity. Four of these nucleosides (6b-9b) were significantly toxic to both HEp-2 and L1210 cells in culture but the most cytotoxic one (9b) was inactive against the P388 leukemia in mice. None of these nucleosides showed significant antiviral activity against Herpes Simplex 1 or 2, vaccinia, or influenza A.     

Three Antinematodal Diterpenes from Euphorbia kansui

Three compounds, 20-O-acetyl-[3-O-(2′E,4′Z)-decadienoyl]-ingenol (1), 20-O-acetyl-[5-O-(2′E,4′Z)-decadienoyl]-ingenol (2) and 3-O-(2′E,4′Z)-decadienoylingenol (3), were isolated from Euphorbia kansui under the bioassay-guided method. Each compound showed the same antinematodal activity against the nematode, Bursaphelenchus xylophilus, at a minimum effective dose (MED) of 5 μg/cotton ball.     

Facile Method for the Preparation of 7-Methyl-8-oxoguanosines as an Immunomodulator¶

Abstract

Reaction of 9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-7-methylguaninium iodide (2a) with hydrogen peroxide in acetic acid gave the corresponding 7-methyl-8-oxoguanosine derivative (3a) in good yield. Deprotection of 3a easily gave 7-methyl-8-oxoguanosine (1), which is well-known as an immunomodulator. Substitution of acetyl group at the N-position of guanine ring accelerated the oxidation reaction of the 7-methylguaninium iodide.

     

Reaction of acylated methyl arabinosides with hydrogen bromide

Treatment of methyl tri-O-acetyl-β-D-arabinopyranoside (1a) with hydrogen bromide in benzene or in acetic acid gave, in addition to the pyranosyl bromide (2a), a considerable proportion of tri-O-acetyl-D-arabinofuranosyl bromide (5). Similar treatment of methyl tri-O-benzoyl-β-D-arabinopyranoside (1b) gave a good yield of the pyranosyl bromide (2b); no furanoid derivative was formed. Ring contraction also took place when methyl 4-O-acetyl-2,3-di-O-benzoyl-β-D-arabinopyranoside (7) was treated with hydrogen bromide, whereas the isomeric 3-O-acetyl-2,4-di-O-benzoyl compound (12) gave the pyranosyl bromide 13 in high yield. Thus, methyl pyranosides with an O-acetyl group at C-4 undergo ring contraction on treatment with hydrogen bromide. The corresponding compounds with O-benzoyl groups at C-4 gave pyranosyl bromides only.     

Electrochemical bromochlorination of peracetylated glycals

Peracetylated glycals—3,4,5-tri-O-acetyl-d-glucal (1a), 3,4,5-tri-O-acetyl-d-galactal (1b) and 3,4-di-O-acetyl-6-deoxy-l-glucal (1c)—have been bromochlorinated by a suitable halogenating agent, generated electrochemically from a mixture of bromides and chlorides in dichloromethane. The reaction was performed in two ways: (i) by a constant current electrolysis (2 F mol⁻¹) of bromides and substrates in a milieu containing an excess of chlorides (Br^?/1/Cl^? = 1:1:6.8) and (ii) by anodic generation of free chlorine from chlorides (2 F mol⁻¹) and subsequent addition of bromides and substrates in a ratio Br^?/1 = 1:1. The corresponding 2-bromo-2-deoxy-glycopyranosyl chlorides were obtained in high yields.     

Ribosylation of the Base Residue of Inosine Derivatives by Phase-Transfer Catalysis

Abstract

Reaction of 2′,3′,5′-O-silylated inosine derivative 1 with 2, 3-O-isopropylidene-5-O-tritylribosyl chloride (3) in a two-phase (CH₂Cl₂-aq. NaOH) system in the presence of Bu₄NBr gave three products, i. e., 6-O-α-, 6-O-β-, and N ¹-β-isomers of glycosides 4, 5a, and 5b. A similar PTC reaction of 1 with 2, 3, 5-tri-O-benzylribosyl bromide (9) gave four regio- and stereo-isomers involving the N¹-β-glycoside 10. Reaction of 1 with 2, 3, 5-tri-O-benzoylribosyl bromide (11) afforded three products involving the desired N¹-β-glycoside 12b, which could be deprotected to give N ¹-ribosylinosine (15b) as a useful intermediate for the synthesis of cIDPR.