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.     

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.     

Syntheses of 6,8-disubstituted-9-β-D-ribofuranosylpurine 3′,5′-cyclic phosphates

A series of 6,8-disubstituted-9-β-D-ribofuranosylpurine 3′,5′-cyclic phosphates were prepared employing preformed 9-β-D-ribofuranosylpurine 3′,5′-cyclic phosphate precursors. Three synthetic approaches were utilized to accomplish the syntheses. The first approach involved a study of the order of nucleophilic substitution, 6 vs 8, of the intermediate 6,8-dichloro-9-β-D-ribofuranosyipurine 3′,5′-cyclic phosphates ( 2 ) with various nucleophilic agents to yield 8-amino-6-chloro-, 8-chloro-6-(diethylamino)-, 6-chloro-8-(diethylamino)-, 6,8-bis-(diethylamino)- and 8-(benzylthio)-6-chloro-9-β-D-ribofuranosylpurine 3′,5′-cyclic phosphate (4, 9, 10, 11, 13) respectively and 6-chloro-9-β-D-ribofuranosylpurin-8-one 3′,5′-cyclic phosphate ( 5 ) and 8-amino-9-β-D-ribofuranosylpurine-6-thione 3′,5′-cyclic phosphate ( 6 ). The order of substitution was compared to similar substitutions on 6,8-dichloropurines and 6,8-dichloropurine nucleosides. The second scheme utilized nucleophilic substitution of 6-chloro-8-substituted-9-β-D-ribofuranosylpurine 3′,5′-cyclic, phosphates obtained from the corresponding 8-subslituted inosine 3′,5′-cyclic phosphates by phosphoryl chloride, 6,8-bis-(benzylthio)-, 6-(diethylamino)-8-(benzylthio),8-(p-chlorophenylthio(-6-(diethylamino)- and 6,8-bis-(methyl-thio)-9-β-D-ribofuranosylpurine 3′,5′-cyclic phosphates ( 14, 12, 20 , and 21 ) respectively, were prepared in this manner. The final scheme involved N¹-alkylation of an 8-substituted adenosine 3′,5′-cyclic phosphate followed by a Dimroth rearrangement to give 6-(benzylamino)-8-(methylthio)- and 6-(benzylamino)-8-bromo-9-β-D-ribofuranosylpurine 3′,5′-cyclic phosphate ( 24 and 25 ).     

Synthesis of 8-amino-9-β-D-ribofuranosylpurin-6-thione and related 6-substituted-8-aminopurine nucleosides

Acetylation of 8-amino-9-β-D-ribofuranosylpurin-6-one (III), followed by chlorination of the tetraacetyl derivative 8-acetamido-9-(2,3,5-tri-O-aeetyl-β-D-ribofuranosyl)purin-6-one (IV) with phosphorus oxychloride yielded 8-aeetamido-6-ehloro-9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-purine (V). The 6-chloro substitutent of V was readily displaced with thiourea to give, after treatment with sodium methoxide 8-acetamido-9-β-D-ribofuranosylpurine-6-thione (VIII). Chlorination of 8-bromo-9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)purin-6-one (IX) yielded 6,8-dichloro-9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)purine (X), which underwent nucleophilic displacement with ethanolic ammonia selectively in the 8 position. The resulting 8-amino-6-chloro-9-β-D-ribofuranosylpurine (VII) was converted to 8-amino-9-β-D-ribofuranosylpurine-6-thione (I), 8-amino-6-methylthio-9-β-D-ribofuranosylpurine (II), and to 8-amino-6-hydrazino-9-β-D-ribofuranosylpurine (XI).     

Synthesis of 5′-halo-2′,3′-lyxo-epoxy and 2′,3′-unsaturated thieno[3,2-d]pyrimidine nucleosides

A series of thieno[3,2-d]pyrimidine-2,4-dione nucleosides modified in the carbohydrate moiety has been synthesized. In the first part, synthetic routes are described for the replacement of 5′-hydroxyl group in preformed 1-(β-D-ribofuranosyl)thieno[3,2-d]pyrimidine-2,4-dione I by fluoro, iodo or chloro atoms. Reduction of the 5′-iodo substituent of VI was then carried out catalytically using palladium on carbon as catalyst to give the expected 5′-deoxy derivative VIII. The lyxo-epoxide derivative XII was then synthesized by sequential treatment of the 5′-deoxy-5′-chloro derivative X with methanesulfonyl chloride and with sodium hydroxide. In the second part, most of attention has been devoted to apply different methods reported in the literature that allow access to 2′,3′-olefinic derivatives from the corresponding 2′,3′-dihydroxy precursor. The 5′-O-silyl protected bisxanthate XIV either on reduction with tri-n-butyltin hydride or by reductive elimination of the haloacetate XVI afforded the free 2′,3′-olefin nucleoside after removal of the 5′-protecting group. However none of the compounds in this series exhibited significant antiviral activity against HIV at the doses tested.     

(±)-5′-Nor ribofuranoside carbocyclic guanosine

The synthesis of the guanine derivative (±)-2-amino-1,9-dihydro-9-[(1′α,2′β,3′β,4′α)-(2′,3′,4′-trihydroxy-1′-cyclopentyl]-6H-purin-6-one ( 2 ) is described. This compound is viewed as the carbocyclic ribofuranoside guanine nucleoside analogue lacking the 5′-methylene.     

Synthesis of 1′,3′-Dioxolan-2′-one by the Reaction of Steroidal Oxiranes with Carbon Dioxide: Synthesis of Five-Membered Cis Cyclic Carbonates

The reaction of 3β-acetoxy-5,6α-epoxy-5α-cholestane 1, its 3β-chloro analogue 2, and 5,6α-epoxy-5α-cholestane 3 with carbon dioxide gas in the presence of sodium bromide as catalyst with continuous stirring at 100 °C for 30 min affords selectively the corresponding 1′,3′,-dioxolan-2′-ones (steroidal cyclic cis-carbonates) 4–6 in excellent yields. The structures of these products have been established on the basis of their elemental analysis and spectral data (infrared, ¹H NMR, and mass).     

Isolation and Characterisation of (5R, 6S,5′R,8′R)- and (5R,6S,5′R,8′S)-Luteochrome from Brazilian Sweet Potatoes (Ipomoea batatas LAM.)

Luteochrome isolated from the tubers of a white-fleshed variety of sweet potato (Ipomoea batatas LAM .) has been shown by HPLC, ¹H-NMR and CD spectra to consist of a mixture of (5R,6S,5′R,8′R)- and (5R,6S,5′R,8′S)- 5,6:5′,8′-diepoxy-5,6,5′,8′-tetrahydro-β,β-carotene ( 1 and 2 , resp.). Therefore, its precursor is (5R,6S,5′R,6′S)-5,6:5′,6′-diepoxy-5,6,5′,6′-tetrahydro-β,β-carotene ( 4 ). This is the first identification of luteochrome as a naturally occurring carotenoid and, at the same time, gives the first clue to the as yet unknown chirality of the widespread β,β-carotene diepoxide. These facts demonstrate that the enzymic epoxidation of the β-end group occurs from the α-side, irrespective of the presence of OH groups on the ring.     

The use of the wittig reaction in the modification of purine nucleosides

The Pfitzner-Moffatt oxidation of 6-chloro-9-(2,3-O-isopropylidene-β-D-ribofuranosyl)purine, 9-(2,3-O-isopropylidene-β-D-ribofuranosyl)-6-(methylthio)purine, and 2′,3′-O-isopropylideneadenosine gave the corresponding 5′-aldehydes (3, 13, and 4), which were allowed to react with a number of Wittig ylids. The resulting olefins, primarily trans, were reduced either catalytically or with diimide before removal of the 2′,3′-O-isopropylidene groups to give the desired 5′-substituted purine ribonucleosides.     

Antifertility Agent: Stereoselective Synthesis of Spiro[cyclopropane-1,7′-yuehchukene]

A facile synthesis of 6′β-(indol-3″-yl)-9′- methyl-5′,6′,-6′αβ,7′,8′,10′ αβ-hexahydrospiro[cyclopropane-1,7′-indeno[2,1-b]indole] (2), an analogue of yuehchukene (1), is described.     

The synthesis of 2-chloro-1-β-D-ribofuranosyl-5,6-dimethylbenzimidazole and (certain related derivatives

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

Selectively Deoxygenated Derivatives of β-Maltosyl-(1→4)-Trehalose as Biological Probes

ABSTRACT

The four derivatives of β-maltosyl-(1→4)-trehalose have been synthesized, which are monodeoxygenated at the site of one of the primary hydroxyl groups. The tetrasaccharides were constructed in [2+2] block syntheses. Thus, 6′″-deoxy-β-maltosyl-(1→4)-trehalose was prepared by selective iodination of allyl 2,3,6,2′,3′-penta-O-acetyl-β-maltoside (3) followed by catalytic hydrogenolysis and coupling with 2,3-di-O-benzyl-4,6-O-benzylidene-α-D-glucopyranosyl 2′,3′,6′-tri-O-benzyl-α-D-glucopyranoside (9), and 6″-deoxy-β-maltosyl-(1→4)-trehalose by selective iodination of allyl 4′,6′-O-isopropylidene-β-maltoside (14), coupling with 9, and one-step hydrogenolysis at the tetrasaccharide level. For the synthesis of 6′-deoxy-β-maltosyl-(1→4)-trehalose, the diol 2,3-di-O-benzyl-4,6-O-benzylidene-α-D-glucopyranosyl 2′,3′-di-O-benzyl-α-D-glucopyranoside (22) was selectively iodinated and glycosylated with acetobromomaltose followed by catalytic hydrogenolysis. The 6-deoxy-β-maltosyl-(1→4)-trehalose was obtained upon selective iodination of a tetrasaccharide diol.     

The synthesis of 3-deazaorotidine and related nucleoside derivatives of 4-hydroxy-2-pyridone

Condensation of 6-earbethoxy-4-hydroxy-2-pyridone or a silyl derivative of 5-earbomethoxy-4-hydroxy-2-pyridone with 2′,3′,5′-tri-O-benzoyl-D-ribofuranosyl halide has provided the 3-deaza analogs of orotidine and uridine-5-carboxylic acid. The corresponding amides have also been prepared in view of their possible structural relationship to l-β-D-ribohiranosyl nicotinamide. Tri-O-benzoyl-3-deazauridine was treated with N-bromosuccinimide to give, after deblocking, 3-bromo-4-hydroxy-1-(β-D-ribofuranosyl)-2-pyridone. The anomeric configuration of these nuclcosides was confirmed by pmr spectroscopy.     

Effect of Substituents,Solvent, and Temperature on the Reactivity of the Zwitterionic Peroxides Arising from the Photo-Oxygenation of 2-(Methoxymethylidene)- and 2-(Phenoxymethylidene)adamantane

The photo-oxygenation of 2-(methoxymethylidene)adamantane ( 3 ) creates a zwitterionic peroxide which may be captured by acetaldehyde to give the corresponding pair of diastereoisomeric tricyclo[3.3.1.1^3,7]decane-2-spiro-6′ -(3′ -methyl-5′ -methoxyl′, 2′, 4′ -trioxanes) ( 4 ). Ease of capture depends strongly on solvent polarity and temperature. When these are low, yields of trioxine are high (～ 80%). Conversely, 1,2-dioxetane formation is favoured at high temperature and solvent polarity. 2-(Phenoxymethylidene)adamantane ( 5 ), on photo-oxygenation, only gives the corresponding 1,2-dioxetene, even in the presence of acetaldehyde. From a Hammett, study of the-oxygenation of the enol ether 5 and p-methoxy, p-methyl, p-chloro and m-chloro derivatives, 9, 11, 13 , and ( 15 ), a good linear relation was found between substituent constants and oxygenation rates which yielded reaction constants (ρ) of 2.59, ?2.40, ?1.09, and ?0.90 in benzene, AcOET, CH₂Cl₂, and MeOH respectively. This data to the formation of a zwitterionic peroxide which enjoys stabilization from its won substituents and by competing solvation and further explains the predominance of dioxetane to the detriment of trioxane formation.     

Epoxidierung von Cucurbitaxanthin A: Herstellung von Cucurbitaxanthin B und seines 5′,6′-Epimeren

Epoxidation of Cucurbitaxanthin A: Preparation of Cucurbitaxanthin B and of Its 5′,6′-Epimer Cucurbitaxanthin A (= (3S,5R,6R,3′S)-3,6-epoxy-5,6-dihydro-β,β-carotene-5,3′-diol; 1 ) isolated from red pepper (Capsicum annuum var. longum nigrum) was trimethylsiylated and then epoxidized with monoperphthalic acid. After deprotection and chromatographic separation, cucurbitaxanthin B (= (3S,5R,6R, 3′S,5′R,6′S)-3,6:5′,6′-diepoxy-5,6,5′,6′-tetrahydro-β,β-carotene-5,3′-diol; 2 ) and 5′,6′-diepicucurbitaxanthin B (= (3S,5R,6R, 3′S,5′S,6′R)-3,6:5′,6′-diepoxy-5,6,5′,6′-tetrahydro-β,β-carotene-5,3′-diol; 5 ) were obtained and carefully characterized. They show mirror-like CD spectra and, therefore, emphasize the importance of the torsion angle of C(6)–C(7) on the electronic interaction between the polyene chain and the chiral end group.     

Direct sulfhydrolysis of cyclic AMP: A one-step synthesis of the cyclic ribonucleotide of 6-mercaptopurine

Treatment of adenosine cyclic 3′,5′-phosphate with liquid H₂S in aqueous pyridine provided a convenient, one-step synthesis of 9-β-D-ribofuranosylpurine-6(1H) thione cyclic 3′,5′-phosphate.     

Synthesis and properties of 5-(1,2-dihaloethyl)-2′-deoxyuridines and related analogues

The regiospecific reaction of 5-vinyl-3′,5′-di-O-acetyl-2′-deoxyuridine ( 2 ) with HOX (X = Cl, Br, I) yielded the corresponding 5-(1-hydroxy-2-haloethyl)-3′,5′-di-O-acetyl-2′-deoxyuridines 3a-c . Alternatively, reaction of 2 with iodine monochloride in aqueous acetonitrile also afforded 5-(1-hydroxy-2-iodoethyl)-3′,5′-di-O-acetyl-2′-deoxyuridine ( 3c ). Treatment of 5-(1-hydroxy-2-chloroethyl)- ( 3a ) and 5-(1-hydroxy-2-bromoethyl)-3′,5′-di-O-acetyl-2′-deoxyuridine ( 3b ) with DAST (Et₂NSF₃) in methylene chloride at -40° gave the respective 5-(1-fluoro-2-chloroethyl)- ( 6a , 74%) and 5-(1-fluoro-2-bromoethyl)-3′,5′-di-O-acetyl-2′-deoxyuridine ( 6b , 65%). In contrast, 5-(1-fluoro-2-iodoethyl)-3′,5′-di-O-acetyl-2′-deoxyuridine ( 6e ) could not be isolated due to its facile reaction with methanol, ethanol or water to yield the corresponding 5-(1-methoxy-2-iodoethyl)- ( 6c ), 5-(1-ethoxy-2-iodoethyl)- ( 6d ) and 5-(1-hydroxy-2-iodoethyl)-3′,5′-di-O-acetyl-2′-deoxyuridine ( 3c ). Treatment of 5-(1-hydroxy-2-chloroethyl)- ( 3a ) and 5-(1-hydroxy-2-bromoethyl)-3′,5′-di-O-acetyl-2′-deoxyuridine ( 3b ) with thionyl chloride yielded the respective 5-(1,2-dichloroethyl)- ( 6f , 85%) and 5-(1-chloro-2-bromoethyl)-3′,5′-di-O-acetyl-2′-deoxyuridine ( 6g , 50%), whereas a similar reaction employing the 5-(1-hydroxy-2-iodoethyl)- compound 3c afforded 5-(1-methoxy-2-iodoethyl)-3′,5′-di-O-acetyl-2′-deoxyuridine ( 6c ), possibly via the unstable 5-(1-chloro-2-iodoethyl)-3′,5′-di-O-acetyl-2′-deoxyuridine intermediate 6h . The 5-(1-bromo-2-chloroethyl)- ( 6i ) and 5-(1,2-dibromoethyl)-3′,5′-di-O-acetyl-2′-deoxyuridine ( 6j ) could not be isolated due to their facile conversion to the corresponding 5-(1-ethoxy-2-chloroethyl)- ( 6k ) and 5-(1-ethoxy-2-bromoethyl)-3′,5′-di-O-acetyl-2′-deoxyuridine ( 61 ). Reaction of 5-(1-hydroxy-2-bromoethyl)-3′,5′-di-O-acetyl-2′-deoxyuridine ( 3b ) with methanolic ammonia, to remove the 3′,5′-di-O-acetyl groups, gave 2,3-dihydro-3-hydroxy-5-(2′-deoxy-β-D-ribofuranosyl)-furano[2,3-d]pyrimidine-6(5H)-one ( 8 ). In contrast, a similar reaction of 5-(1-fluoro-2-chloroethyl)-3′,5′-di-O-acetyl-2′-deoxyuridine ( 6a ) yielded (E)-5-(2-chlorovinyl)-2′-deoxyuridine ( 1b , 23%) and 5-(2′-deoxy-β-D-ribofuranosyl)furano[2,3-d]pyrimidin-6(5H)-one ( 9 , 13%). The mechanisms of the substitution and elimination reactions observed for these 5-(1,2-dihaloethyl)-3′,5′-di-O-acetyl-2′-deoxyuridines are described.     

Nucleotides. Part XXXIVSynthesis of Modified Oligomeric 2′–5′A Analogues: Potential Antiviral Agents

A series of new 2′–5′-oligonucleotide trimers carrying a 9-(2′,3′-anhydro-β-D -ribofuranosyl)-( 59 ), 9-(3′-deoxy-β-D -glycero-pent-3-enofuranosyl)-( 63 ), 9-(3′-azido-3′-deoxy-β-D -xylofuranosyl)-( 62 ), and 9-(3′-halo-3′-deoxy-β-D -xylofuranosyl)adenine ( 60 and 61 ) moiety at the 2′-terminal end have been synthesized via the phosphotriester method. The properly protected, modified monomeric building blocks ( 6 , 9 , 16 , 19 , 27 , 33 , 36 , 37 , and 43 ) were obtained, in general, by a sequence of reactions, introducing the protecting groups into the right positions. Their condensations with the intermediary dimeric 2′-terminal phosphodiesters 48 and 49 led to the fully protected 2′–5′-trimers 50–58 which were deblocked to form the free 2′–5′-trimers 59 – 63 . Easy elimination of HBr on deprotection did not allow to form the trimeric (3′-bromo-3′-deoxy-β-D -xylofuranosyl)adenine analogue but only 63 carrying an unsaturated sugar moiety instead. The newly synthesized compounds have been characterized by UV and NMR spectra as well as by elemental analysis.     

Selectively Deoxygenated Derivatives of β-Maltosyl-(1→4)-Trehalose as Biological Probes. II. the Synthesis of the 4- and 4′″-Monodeoxygenated Analogues

ABSTRACT

Two derivatives of β-maltosyl-(1→4)-trehalose monodeoxygenated at positions 4 or 4′″ have been synthesized in [2+2] block syntheses. After the preparation of precursors with only one free hydroxyl group the deoxy function was introduced by a Barton-McCombie reaction. Thus, glycosylation of 2,3,6-tri-O-benzyl-α-D-glucopyranosyl 2,3,6-tri-O-benzyl-α-D-glucopyranoside (4) with octa-O-acetyl-β-maltose (3) gave tetrasaccharide 5 with only one free hydroxyl group at the 4-position. The 4′-position of an allyl maltoside was available selectively after removal of a 4′,6′-cyclic acetal and selective benzoylation of the 6′-position. Reduction of this derivative 11 afforded allyl O-(2,3-di-O-acetyl-6-O-benzoyl-4-deoxy-α-D-glucopyranosyl)-(1→4)-2,3,6-tri-O-acetyl-β-D-glucopyranoside (14), which was deallylated, activated as an trichloroacetimidate, and coupled to 2,3-di-O-benzyl-4,6-O-benzylidene-α-D-glucopyranosyl 2′,3′,6′-tri-O-benzyl-α-D-glucopyranoside (20). Several compounds were fully characterized by ¹H NMR spectroscopy. Deprotection furnished the monodeoxygenated tetrasaccharides 9 and 23.     

Synthesis of 6-alkyl and 6-aryl substituted 9-β-D-ribofuranosyl purines via the nickel catalyzed coupling of grignard reagents to 2′,3′,5′-tris-0-(t-butyldimethylsilysl)-9-β-D-ribofuranosyl-6-chloropurine

A series of 6-substituted purine nucleosides have been synthesized in moderate yield by the nickel catalyzed cross coupling reaction between alkyl- and aryl- Grignard reagents and 2′,3′,5′-tris-0-(t-butyldimethylsilyl)-9-β-$\text{D}$-ribofuranosyl-6-chloropurine.