A convenient synthesis of certain 1-(β-D-ribofuranosyl)benzotriazoles

The synthesis of 5,6-dichloro-1-(β-D -ribofuranosyl)benzotriazole ( 4a ), 5,6-dimethyl-1-(β-D -ribofuranosyl)benzotriazole ( 4b ) and 1-(β-D -ribofuranosyl)benzotriazole ( 4c ) in good yield has been accomplished by the condensation of the appropriate 1-trimethylsilylbenzotriazole ( 1a, 1b , and 1c ) with 2,3,5-tri-O-acetyl-D -ribofuranosyl bromide (2) followed by subsequent deacetylation of the reaction products. The assignment of anomeric configuration and site of glycosidation for all nucleosides reported is discussed.     

Synthesis and chemistry of some pyridazine nucleosides related to certain 5-substituted pyrimidine nucleosides

Condensation of 3,4-dichloro-6-[(trimethylsilyl)oxy] pyridazine ( 3 ) with 1-O-acetyl-2,3,5-tri-O-benzoyl-β- D -ribofuranose ( 4 ), by the stannic chloride catalyzed procedure, has furnished 3,4-dichloro-1-(2,3,5-tri-O-benzoyl-β- D -ribofuranosyl) pyridazin-6-one ( 5 ). Nucleophilic displacement of the chloro groups and removal of the benzoyl blocking groups from 5 has furnished 3-chloro-4-methoxy-, 3,4-dimethoxy-, 4-amino-3-chloro-, 3-chloro-4-methylamino-, 3-chloro-4-hydroxy-, and 4-hydroxy-3-methoxy-1-β- D -ribofuranosylpyridazin-6-one. An unusual reaction of 5 with dimethylamine is reported. Condensation of 4,5-dichloro-3-nitro-6-[(trimethylsilyl)oxy]pyridazine with 4 yielded 4,5-dichloro-3-nitro-1-(2,3,5-tri-O-benzoyl-β- D -ribofuranosyl)pyridazin-6-one ( 24 ). Nucleophilic displacement of the aromatic nitro groups from 24 is discussed. Condensation of 3 with 3,5-di-O-p-toluoyl 2-deoxy- D -erythro-pentofuranosyl chloride ( 28 ) afforded an α, β mixture of 2-deoxy nucleosides. The synthesis of certain 3-substituted pyridazine 2′-deoxy necleosides are reported.     

The synthesis of 2-chloro-1-(β-D-ribofuranosyl)benzimidazole and certain related derivatives

The synthesis of 2-chloro-1-(β-D-ribofuranosyl)benzimidazole (4b) has been accomplished by a condensation of 2-chloro-1-trimethylsilylbenzimidazole (1) with 2,3,5-tri-O-acetyl-D-ribofuranosyl bromide (2) followed by subsequent deacetylation. Nucleophilic displacement of the 2-chloro group has furnished several interesting 2-substituted-1-(β-D-ribofuranosyl)benzimidazoles. 1-(β-D-Ribofuranosyl)benzimidazole (5) and 1-(β-D-ribofuranosyl)benzimidazole-2-thione (6) were prepared from 4b and 6 was also prepared by condensation of 2 with silylated benzimidazole- 2-thione (3). Alkylation of 6 furnished certain 2-alkylthio-1-(β-D-ribofuranosyl)benzimidazoles and oxidation of 6 with alkaline hydrogen peroxide produced 1-(β-D-ribofuranosyl)benzimidazole-2-one (9). The assignment of anomeric configuration for all nucleosides reported is discussed.     

Nucleosides and nucleotides. Part 25.. Synthesis of a protected 1-(2′-deoxy-β-D-ribofuranosyl)-1 H-benzimidazole 3′-phosphate

1-(2′-Deoxy-5′-O-dimethoxytrityl-′-D -ribofuranosyl)-1 H-benzimidazole 3′-[(p-chlorophenyl)(2-cyanoethyl) phosphate] ( 6 ) has been synthesized from 1-(β-D -ribofuranosyl)-1H-benzimidazole ( 3b ) using regiospecific 2′-deoxygenation. The latter compound was obtained by glycosylation of benzimidazole with the D -ribose derivative 2 leading exclusively of the β-D -anomer.     

The synthesis of 3-(β-D-ribofuranosyl)imidazo[4,5-c] pyridazines

7-Chloro-3-(β- D -2,3,5-tri-O-benzoylribofuranosyl)imidazo[4,5-c] pyridazine ( 3 ), obtained from the condensation of 7-chloro-3-trimethylsilylimidazo[4,5-c] pyridazine ( 1 ) with 2,3,5-tri-O-benzoyl- D -ribofuranosyl bromide ( 2 ), served as the percursor of 7-chloro- ( 4 ), 7-amino- ( 8 ), and 7-mercapto-3-(β- D -ribofuranosyl)imidazo[4,5-c] pyridazine ( 9 ). 3-(β- D -ribofuranosyl)imidazo[4,5-c] pyridazine ( 7 ) was obtained from 3-(β- D -2,3,5-tri-O-benzoylribofuranosyl)imidazo-[4,5-c]pyridazine ( 6 ). The site of ribosidation is based upon uv spectral comparisons with model methyl compounds. The assignment of the anomeric configuration is derived from pmr spectral data.     

Nucleoside und Nucleotide. Teil 16. Verhalten von 1-(2′-Desoxy-β-D-ribofuranosyl)-2(1 H)-pyrimidinon-5′-triphosphat, 1-(2′-Desoxy-β-D-ribofuranosyl)-2(1 H)pyridinon-5′-triphosphat und 4-Amino-1-(2′-Desoxy-β-D-ribofuranosyl)-2(1 H)-pyridinon-5′-triphosphat gegenüber DNA-Polymerase

Nucleosides and Nucleotides. Part 16. The Behaviour of 1-(2′-Deoxy-β-D -ribofuranosyl)-2(1H)-pyrimidinone-5′-triphosphate, 1-(2′-Deoxy-β-D -ribofuranosyl-2(1H))-pyridinone-5′-triphosphate and 4-Amino-1-(2′-desoxy-β-D -ribofuranosyl)-2(1H)-pyridinone-5′-triphosphate towards DNA Polymerase The behaviour of nucleotide base analogs in the DNA synthesis in vitro was studied. The investigated nucleoside-5′-triphosphates 1-(2′-deoxy-β-D -ribofuranosyl)-2(1 H)-pyrimidinone-5′-triphosphate (pppM_d), 1-(2′-deoxy-β-D -ribofuranosyl)-2(1 H)-pyridinone-5′-triphosphate (pppII_d) and 4-amino-1-(2′-deoxy-β-D -ribofuranosyl)-2(1 H)-pyridinone-5′-triphosphate (pppZ_d) can be considered to be analogs of 2′-deoxy-cytidine-5′-triphosphate. However, their ability to undergo base pairing to the complementary guanine is decreased. When pppM_d, pppII_d or pppZ_d are substituted for pppC_d in the enzymatic synthesis of DNA by DNA polymerase no incorporation of these analogs is observed. They exhibit only a weak inhibition of the DNA synthesis. The mode of the inhibition is uncompetitive which shows that these nucleotide analogs cannot serve as substrates for the DNA polymerase.     

4-Oxa(thia)-9-oxa-2-azabicyclo[4.2.1]nonane-3-on(thion) derivatives

The synthesis of 7,8-dihydroxy-2-(2-methoxycarbonylethyl)-4,9-dioxa-2-azabicyclo[4.2.1]nonane- 3-thione ( 16 ) and of its parents 9-oxa-4-thia-3-thione 17 , and 9-oxa-4-thia-3-one 18 is described. The conversion of 5′-deoxy-5′-iodo-2′,3′-O, O-isopropylidene-5,6-dihydrouridin ( 1 ) into the 2-O-methyl-5,6-dihydrouridine 5 , the 5′-O-acetyl-5,6-dihydrouridine 4 , and into the N-(5-O-acetyl-2,3-O, O-isopropylidene-β-D -ribofuranosyl)-N-(2-methoxycarbonyl thyl)-urea ( 6 ) invoked 2′,3′-O, O-isopropylidene-2,5′-anhydro-5,6-dihydrouridine ( 2 ) as the common intermediate.     

The synthesis of certain ribofuranosylindazoles

The synthesis of 1-(β-D-ribofuranosyl)indazole (4), 2-(β-D-ribofuranosyl)indazole (5) and 6-, 5-, and 4-nitro-2-(β-D-ribofuranosyl)indazole (8a, 8b, and 8c, respectively), has been accomplished in good yield by the condensation of the appropriate N-trimethylsilylindazole (1, 6a, 6b, and 6c) with 2,3,5-tri-O-acetyl-D -ribofuranosyl bromide (2) followed by subsequent deacetylation of the reaction products. The site of ribosylation and the assignment of anomeric configuration for all nucleosides reported is discussed. This has furnished the first indazole nucleosides with assigned anomeric configurations and the site of ribosylation has been established on the basis of uv comparisons with model methyl compounds.     

Pyrazolopyrimidine nucleosides. Part VII. The synthesis of certain pyrazolo [3,4-d] pyrimidine nucleosides related to the nucleoside antibiotics toyocamycin and sangivamycin

The condensation of 4-acetamido-3-cyanopyrazolo[3,4-d]pyrimidine ( 5 ) with crystalline 2,3,5-tri-O-acetyl-β- D -ribofuranosyl chloride ( 6 ) has furnished a good yield of nucleoside material ( 7 ) which on treatment with sodium methoxide in methanol provided a high yield of nucleoside which was subsequently established as methyl 4-amino-1-(β- D -ribofuranosyl)pyrazolo[3,4-d]-pyrimidine-3-formimidate monohydrate ( 11 ). The formimidate function of 11 was found to be highly reactive and 11 was readily converted into the corresponding carhoxamidine ( 8 ), carboxamidoxime ( 14 ) and carboxamidrazone ( 15 ) when treated with the appropriate nucleophiles. Treatment of the imidate ( 11 ) with sodium hydrogen sulfide gave a high yield of the thiocarboxamide ( 12 ) which was then readily converted into 4-amino-3-cyano-1-(β- D -ribofuranosyl)pyrazolo[3,4-d]pyrimidine ( 16 ). Aqueous base transformed 11 into 4-amino-1-(β- D -ribofuranosyl)-pyrazolo[3,4-d]pyrimidine-3-carboxamide ( 10 ) while more vigorous basic hydrolysis provided the corresponding carboxylic acid ( 9 ) in nearly quantitative yield. Decarboxylation of 9 proceeded smoothly in hot sulfolane to provide the known 4-amino-1-(β- D -ribofuranosyl)pyrazolo[3,4-d]pyrimidine ( 13 ) in 68% yield which unequivocally established the site of ribosylation and anomeric configuration for all nucleosides reported in this investigation.     

Pyrrolopyrimidine nucleosides. IV. The synthesis of certain 4,5-disubstituted-7-(β-d-ribofuranosyl)pyrrolo[2,3-d]pyrimidines related to the pyrrolo[2,3-d]pyrimidine nucleoside antibiotics

The treatment of 4-chloro-7-(2′,3′,5′-tri-O-acetyl-β-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidine ( 4 ) with N-bromoacetamide in methylene chloride has furnished the 5-bromo derivative of 4 which on subsequent deacetylation provided a good yield of 5-bromo-4-chloro-7-(β-D-ribo-furanosyl)pyrrolo[2,3-d] pyrimidine ( 6 ). Assignment of the halogen substituent to position 5 was made on the basis of pmr studies. Treatment of 6 with methanolic ammonia afforded 4-amino-5-bromo-7-(β-D-ribofuranosyl)pyrrolo[2,3-d ]pyrimidine ( 8 , 5-bromotubercidin) and a subsequent study has revealed that the 4-chloro group of 6 was replaced preferentially in a series of nucleophilic displacement reactions. The analogous synthesis of 4,5-dichloro-7-(β-D-ribo-furanosyl)pyrrolo[2,3-d]pyrimidine ( 13b ) and 4-chloro-5-iodo-7-(β-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidine ( 13a ) from 4 furnished 5-chlorotubercidin ( 15 ) and 5-iodotubercidin ( 14 ), respectively, on treatment of 13b and 13a with methanolic ammonia. The possible biochemical significance of these tubercidin derivatives is discussed.     

Nucleoside und Nucleotide. Teil 15. Synthese von Desoxyribonucleosid-monophosphaten und -triphosphaten mit 2(1H)-Pyrimidinon, 2(1H)-Pyridinon und 4-Amino-2(1H)-pyridinon als Basen

Nucleosides and Nucleotide. Part 15. Synthesis of Deoxyribonucleoside Monophosphates and Triphosphates with 2(1H)-Pyrimidinone, 2(1H)-Pyridinone and 4-Amino-2(1H)-pyridinone as the Bases The phosphorylation of the modified nucleosides 1-(2′-deoxy-β-D -ribofuranosyl)-2(1 H)-pyrimidinone (M_d, 4 ), 4-amino-1-(2′-deoxy-β-D -ribofuranosyl)-2(1 H)-pyridinone (Z_d, 6 ) and the synthesis of 1–2′-deoxy-β-D -ribofuranosyl-2(1 H)-pyrimidinone-5′-O-triphosphate (pppM_d, 1 ), 1-(2′-deoxy-β-D ribofuranosyl)-2(1 H)-pyridinone-5′-O-triphosphate (pppII_d, 2 ), and 4-amino-1-(2′-deoxy-βD -ribofuranosyl)-2(1 H)-pyridinone-5′-O-triphosphate (pppZ_d, 3 ) are described. The nucleoside-5′-monophosphates pM_d (5) and pZ_d (7) were obtained by selective phosphorylation of M_d (4) and Z_d (6) , respectively, using phosphorylchloride in triethyl phosphate or in acetonitril. The reaction of pM_d (5) pII _d (8) or pZ_d (7) with morpholine in the presence of DCC led to the phosphoric amides 9, 10 and 11 , respectively, which were converted with tributylammonium pyrophosphate in dried dimethylsulfoxide to the nucleoside-5′triphosphates 1, 2 and 3 , respectively.     

Synthese von Nucleosiden aus 2-substituierten Imidazolen

Synthesis of 2-Substituted Imidazole Nucleosides Condensation of the trimethylsilyl derivatives of 2-substituted diethyl and dimethyl imidazole-4,5-dicarboxylates ( 3–5 and 7–9 ) with 1-O-acetyl-2,3,5-tri-O-benzoyl-β-D -ribofuranose ( 2 ) in the presence of trimethysilyl trifluoromethanesulfonate provided the 2-substituted diethyl and dimethyl 1-(2′,3′, 5′-tri-O-benzoyl-β-D -ribofuranosyl)imidazole-4, 5-dicarboxylates 10–15 . These were treated with ammonia to afford the 2-substituted 1-(β-D -ribofuranosyl)imidazole-4,5-dicarboxamides 16–21 . Treatment of 2-methyl-( 16 ) and 2-ethyl-1-(β-D -ribofuranosyl)imidazole-4,5-dicarboxamide ( 17 ) with fuming nitric acid in oleum at ?30° yielded the nitric acid esters 23 and 24 . Besides the esterification of the sugar hydroxyl groups one H-atom of the imidazolecarboxamide function at C(5) in these nucleosides was also substituted by the NO₂ group. The conformations in solution of 16 and 23 have been determined by ¹H- and ¹³C-NMR. spectroscopy. These studies indicate that the nucleosides exist in dimethyl-sulfoxide solution preferentially in the S-gg-syn-conformation ( 16 ) and N-gt-conformation ( 23 ). In the crystal structure of nucleoside 23 , the ribose was found to be in the O(1′)_endo, C(1′)_exo twist conformation. The conformation about C(4′), C(5′) is gauche-trans and the molecule exists in the syn form.     

Synthesis of 4H-1,3,4-oxadiazino[5,6-b]quinoxalines from 2-substituted quinoxaline 4-oxides

The reaction of 6-chloro-2-(1-methylhydrazino)quinoxaline 4-oxide 8 with acetic anhydride resulted in the intramolecular cyclization to give 8-chloro-2,4-dimethyl-4H-1,3,4-oxadiazino[5,6-b]quinoxaline 7a , while the reaction of compound 8 with acetic anhydride/pyridine or acetic anhydride/acetic acid afforded 3-(2,2-diacetyl-1-memymydrazmo)-7-chloro-2-oxo-1,2-dihydroquinoxaline 9 , effecting no intramolecular cyclization. The reaction of 2-(2-acetyl-1-methylhydrazino)-6-chloroquinoxaline 4-oxide 10a or 6-chloro-2-(1-methyl-2-trifluoroacetylhydrazino)quinoxaline 4-oxide 10b with phosphoryl chloride provided compound 7a or 8-chloro-4-memyl-2-trifluoromethyl-4H-1,3,4-oxadiazino[5,6-b]quinoxaline 7b , respectively. The reaction of compound 7b with phosphorus pentasulfide gave 7-chloro-3-(1-methyl-2-trifluoroacetylhydrazino)-2-thioxo-1,2-dihydroquinoxaline 11 , whose dehydration with sulfuric acid in acetic acid afforded 8-chloro-4-methyl-2-trifluoromemyl-4H-1,3,4-thiadiazino[5,6-b]quinoxaline 12 .     

A novel and efficient synthesis of the naturally occurring nucleoside doridosine

1-Methylisoguanosine was synthesized by a one-pot reaction involving a condensation of 5-amino-1-(β-$\text{D}$-ribofuranosyl)imidazole-4-carboxamide (1) with methyl isothiocyanate, treatment of the resulting thiourea derivative with DCC furnished 5-(3-methyl-1-ureido)-1-(β-$\text{D}$-ribofuranosyl)imidazole-4-carbonitrile (4) which was then annulated with ethanolic ammonia to furnish doridosine in a 68% yield from 1.     

Nucleosides. Part L.. Structure of lumazine N1-(2′-deoxy-D-ribonucleosides) ( = 1-(2′-deoxy-D-ribofuranosyl)pteridine-2,4(1H,3H)-diones): A revision of the anomeric configuration

The anomeric configuration of the glycosidic bond in lumazine N¹-(2′-deoxy-D -ribonucleosides) 1–6 was investigated by NOE difference spectroscopy. The former configurational assignment of the α - and β -D -anomers 1 and 2, 3 and 4 , and 5 and 6 , respectively, has to be reversed to be in agreement with the physical data. Additional proof is presented by X-ray analysis of 3 and 6 . Chemical interconversions of 1-(2′-deoxy-β-D -ribofuranosyl)-6,7-diphenyllumazine ( 6 ) into 2,3′ -anhydrolumazine 2′-deoxyribonucleosides 16 and 17 are also in agreement with the revised anomeric configuration.     

7-Substituted 7-Deaza-2′-deoxyguanosines: Regioselective Halogenation of Pyrrolo[2,3-d]pyrimidine Nucleosides

The synthesis of 7-chloro-, 7-bromo-, and 7-iodo-substituted 7-deaza-2′-deoxyguanosine derivatives 2b – d is described. The regioselective 7-halogenation with N-halogenosuccinimides was accomplished using 7-[2-deoxy-3,5-O-di(2-methylpropanoyl)-β-D -erythro- pentofuranosyl]-2-(formylamino)-4-methoxy-7H-pyrrolo[2,3-d]- pyrimidine ( 4 ) as the common precursor. A one-pot reaction (2N aq. NaOH) of the halogenated intermediates 5a – c furnished the desired compounds. Also the 7-hexynyl derivative 2e of 7-deaza-2′-deoxyguanosine is described.     

Synthesis, 1H- and 13C-NMR spectra,crystal structure and ring openings of 1-methyl-6,9-epoxy-9-aryl-5,6,9,10-tetrahydro-1H-imidazo [3,2-e] [2H-1,5] oxazocinium methanesulfonate

The methanesulfonic acid catalyzed reaction of 1-(4-chloro- and 2,4-dichlorophenyl)-2-(1-methyl-2-imida-zolyl)ethanones 1a and 1b with glycerol produced cis- and trans-{2-haloaryl-2-[(1-methyl-2-imidazolyl)methyl]-4-hydroxymethyl}-1,3-dioxolanes 2a and 2b with a 2:1 cis/trans ratio. Besides these five-membered ketals, the reaction of 1a with glycerol afforded a small amount of trans-{2-(4-chlorophenyl)-2-[(1-methyl-2-imidazolyl)methyl]-5-hydroxy}-1,3-dioxane ( 3a , 7%). The reaction of methanesulfonyl chloride with cis-1 formed the corresponding methanesulfonates, cis- 4 , which rapidly cyclized to the title compounds 5 . Base-catalyzed ring opening of 5 furnished 1-methyl-5,6-dihydro-6-hydroxymethyl-8-(4-chloro- and 2,4-dichlorophenyl)-1H-imidazo[3,2-d][1,4]oxazepinium methanesulfonates 7 . Acid-catalyzed hydrolyses of 5 or 7 provided 1-methyl-2-[(4-chloro- and 2,4-dichloro)phenacyl]-3-[(2,3-dihydroxy)-1-propyl]imidazolium salts 12 . Structure proofs were based on extensive ¹H and ¹³C chemical shifts and coupling constants and structures of 3a and 5a were confirmed by single crystal X-ray crystallography.     

Synthesis and single-crystal X-ray diffraction studies of 1-β-D-ribofuranosyl-1,2,4-triazole-3-sulfonamide and certain related nucleosides

1-β-D-Ribofuranosyl- 21 , 1-(2-deoxy-β-D-erytftro-pento fur anosyl)- 27 and 1-β-D-arabinofuranosyl- 29 derivatives of 1,2,4-triazole-3-sulfonamide ( 19 ) have been prepared. Glycosylation of the silylated 19 with 1,2,3,5-tetra-0-acetyl-β-D-ribofuranose ( 5 ) in the presence of trimethylsilyl triflate gave the corresponding blocked nucleoside ( 20 ), which on ammonolysis afforded 1-β-D-ribofuranosyl-1,2,4-triazole-3-sulfonamide ( 21 ). Stereospecific glycosylation of the sodium salt of 19 with either 1-chloro-2-deoxy-3,5-di-O-p-toluoyl-α-D-erythro-pentofuranose ( 22 ) or 1-chloro-2,3,5-tri-0-benzyl-α-D-arabinofuranose ( 23 ) provided the corresponding protected nucleosides 26 and 28. Deprotection of 26 and 28 furnished 1-(2-deoxy-β-D-erythro-pentofuranosyl)-1,2,4-triazole-3-sulfonamide ( 27 ) and 1-β-D-arabinofuranosyl-1,2,4-triazole-3-sulfonamide ( 29 ), respectively. 2-0-D-Ribofuranosyl-1,2,4-triazole-3(4H)-thione ( 7 ) and 4-β-D-ribofuranosyl-1,2,4-triazole-3(2H)-thione ( 9 ) were also prepared utilizing either an acid catalyzed fusion of 1,2,4-triazole-3(1H,2H)-thione ( 4 ) with 5 , the reaction of 5 with silylated 4 in the presence of trimethylsilyl triflate, or by ring closure of 4-(2,3,5-tri-0-benzoyl-β-D-ribofuranosyl)thiosemicarbazide ( 10 ) with mixed anhydride and subsequent deacylation. The synthesis of 1-β-D-ribofuranosyl-3-benzylthio-1,2,4-triazole ( 15 ) has also been accomplished by the silylation procedure employing 3-benzylthio-1,2,4-triazole ( 13 ) and 5 to give 1-(2,3,5-tri-0-acetyl-β-D-ribofuranosyl)-3-benzylthio-1,2,4-triazole ( 14 ). Deacetylation of 14 furnished 15 . The structural assignments of 7, 14 and 21 were made by single-crystal X-ray diffraction analysis and their hydrogen bonding characteristics have been studied. The sulfonamido-1,2,4-triazole nucleosides are devoid of any significant antiviral or antitumor activity in cell culture.     

8-Aza-7-deaza-2′,3′-dideoxyguanosine: Deoxygenation of its 2′deoxy-β-D-ribofuranoside

The synthesis of 6-amino-1-(2′,3′-dideoxy-β-D -glycero-pentofuranosyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one ( =8-aza-7-deaza-2′,3′-dideoxyguanosine; 1 ) from its 2′-deoxyribofuranoside 5a by a five-step deoxygenation route is described. The precursor of 5a, 3a , was prepared by solid-liquid phase-transfer glyscosylation which gave higher yields (57%) than the liquid-liquid method. Ammonoloysis of 3b furnished the diamino nucleoside 3c . Compound 1 was less acid sensitive at the N-glycosydic bond than 2′,3′-dideoxyguanosine ( 2 ).     

The synthesis and chemical reactivity of 6-selenoguanosine and certain related derivatives

The synthesis of 6-selenoguanosine ( 2 ) has been accomplished by a nucleophilic displacement of the chloro group from 2-amino-6-chloro-9-(β- D -ribofuranosyl)purine ( 1 ) with either selenourea or sodium hydrogen selenide. Treatment of 2 with Raney nickel has revealed that the seleno group can be removed much easier under these conditions than the corresponding mercapto group. Alkylation of 2 with several alkylating agents occurred at the exocyclic 6-seleno group to furnish several 6-alkylseleno-2-amino-9-(β- D -ribofuranosyl)purines. Nucleophilic displacement of the 6-benzylseleno group from 2-amino-6-benzylseleno-9-(β- D -ribofuranosyl)purine ( 3c ) with sodium methoxide has been observed to occur at a faster rate than that observed for the corresponding 6-benzylmercapto derivative. A study on the relative stability between 2 and 6-seleno-9-(β- D -ribofuranosyl)purine toward basic conditions has revealed that the amino group at position two imparts an increase in stability.