8-Aza-2′-deoxyguanosine and Related 1,2,3-Triazolo[4,5-d]pyrimidine 2′-Deoxyribofuranosides

The synthesis of 8-azaguanine N⁹-, N⁸-, and N⁷-(2′-deoxyribonucleosides) 1–3 , related to 2′-deoxyguanosine ( 4 ), is described. Glycosylation of the anion of 5-amino-7-methoxy-3H-1,2,3-triazolo[4,5-d]pyrimidine ( 5 ) with 2-deoxy-3,5-di-O-(4-toluoyl)-α-D -erythro-pentofuranosyl chloride ( 6 ) afforded the regioisomeric glycosylation products 7a/7b, 8a/8b , and 9 (Scheme 1) which were detoluoylated to give 10a, 10b, 11a, 11b , and 12a . The anomeric configuration as well as the position of glycosylation were determined by combination of UV, ¹³C-NMR, and ¹H-NMR NOE-difference spectroscopy. The 2-amino-8-aza-2′-deoxyadenosine ( 13 ), obtained from 7a , was deaminated by adenosine deaminase to yield 8-aza-2′-deoxyguanosine ( 1 ), whereas the N⁷- and N⁸-regioisomers were no substrates of the enzyme. The N-glycosylic bond of compound 1 (0.1 N HCl) is ca. 10 times more stable than that of 2′-deoxyguanosine ( 4 ).     

Nucleosides and Nucleotides. Part 13. Synthesis and spectral properties of 1- (3′-O-Phosphoryl-2′-deoxy-β -D-ribofuranosyl)-2(1H)-pyridone-(3′-5′)-1-(2′-deoxy-β-D-ribofuranosyl)-2 (1H)-pyridone

The dinucleoside phosphate Π_dpΠ_d ( 4 ) was synthesized from the monomers 1-(5′-O-monomethoxytrityl - 2′ - deoxy - β - D - ribofuranosyl) - 2 (1 H) - pyridone ((MeOTr) Π_d, 2 ) and 1-(5′-O-phosphoryl-3′-O-acetyl-2′-deoxy-β-D -ribofuranosyl)-(1H)-pyridone (pΠ_d(Ac), 3 ). Its 6.4% hyperchromicity and an analysis of the ¹H-NMR. spectra indicate that the conformation and the base-base interactions in 4 are similar to those in natural pyrimidine dinucleoside phosphates.     

1,2-Epoxycarotinoide. 4. Mitteilung. Synthese, 1H-NMR- und CD-Studien von (S)-1,2-Epoxy-1,2-dihydrolycopin und (S)-1′,2′-Epoxy-1′,2′-dihydro-γ-carotin

1,2-Epoxycarotenoids: Synthesis, ¹H-NMR and CD Studies of (S)-1,2-Epoxy-1,2-dihydrolycopene and (S)-1′,2′-Epoxy-1′, 2′ -dihydro-γ-carotene The synthesis of (S)-1,2-epoxy-1,2-dihydrolycopene (^(S)- 1 ) and (S)-1′, 2′ -epoxy- 1′, 2′ -dihydro-γ-carotene ((S)- 2 ) are described. The CD spectra of the (all-E)-isomers and of the isomers (7Z, S)- 1 and (7′Z, S)- 2 are discussed. The comparison of the CD spectra of the synthetic (S)- 1 and the compound isolated from the tomatoes proves the (S)-configuration of the natural product.     

Synthesis of 8-Aza-1,3-dideaza-2′-deoxyadenosine and 5,6-Disubstituted Benzotriazole 2′-Deoxy-β-D-Ribofuranosides via Nucleobase-Anion Glycosylation

The synthesis of 8-aza-1,3-dideaza-2′-deoxyadenosine ( 3a ) as well as of 4- and 5,6-substituted benzotriazole 2′-deoxy-β-D -ribonucleosides is described (Schemes 1–3). Glycosylation of benzotriazole anions is stereoselective in all cases (exclusive β-D -anomer formation), but regioisomeric N¹, N², and N³-(2′-deoxyribofuranosides) are formed. The distribution of the regioisomers is controlled by the nucleobase substituents. Anomeric configuration as well as the position of glycosylation are determined by UV and NMR in combination with 1D-NOE-difference spectroscopy. The unprotonated forms of 4-aminobenzotriazoic 2′-deoxy-β-D -ribofuranosides 3a – c exhibit strong fluorescence.     

2′, 3′-Dideoxy-3′-fluorotubercidin and Related Dideoxyribonucleosides:. Synthesis via a 2′-deoxy-3′-oxoribofuranoside intermediate and conformation studies

An efficient synthesis of the unknown 2′-deoxy-D-threo-tubercidin ( 1b ) and 2′, 3′-dideoxy-3′-fluorotubercidin ( 2 ) as well as of the related nucleosides 9a, b and 10b is described. Reaction of 4-chloro-7-(2-deoxy-β-D-erythro-pentofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine ( 5 ) with (tert-butyl)diphenylsilyl chloride yielded 6 which gave the 3′-keto nucleoside 7 upon oxidation at C(3′). Stereoselective NaBH₄ reduction (→ 8 ) followed by deprotection with Bu₄NF(→ 9a )and nucleophilic displacement at C(6) afforded 1b as well as 7-deaza-2′-deoxy-D-threo-inosine ( 9b ). Mesylation of 4-chloro-7-{2-deoxy-5-O-[(tert-butyl)diphenylsilyl]-β-D-threo-pentofuranosyl}-7H-pyrrolo[2,3-d]-pyrimidine ( 8 ), treatment with Bu₄NF (→ 12a ) and 4-halogene displacement gave 2′, 3′-didehydro-2′, 3′-dideoxy-tubercidin ( 3 ) as well as 2′, 3′-didehydro-2′, 3′-dideoxy-7-deazainosne ( 12c ). On the other hand, 2′, 3′-dideoxy-3′-fluorotubercidin ( 2 ) resulted from 8 by treatment with diethylamino sulfurtrifluoride (→ 10a ), subsequent 5′-de-protection with Bu₄NF (→ 10b ), and Cl/NH₂ displacement. ¹H-NOE difference spectroscopy in combination with force-field calculations on the sugar-modified tubercidin derivatives 1b , 2 , and 3 revealed a transition of the sugar puckering from the ^3′T_2′ conformation for 1b via a planar furanose ring for 3 to the usual ^2′T_3′ conformation for 2.     

Nucleosides. Part LI The 2-(4-nitrophenyl)ethoxycarbonyl (npeoc) and 2-(2,4-dinitrophenyl)ethoxycarbonyl (dnpeoc) groups for protection of hydroxy functions in ribonucleosides and 2′ -deoxyribonucleosides

The Common 2′ -deoxypyrimidine and -purine nucleosides, thymidine ( 4 ), O⁴-[2-(4-nitrophenyl)ethyl]-thymidine ( 17 ), 2′-deoxy-N⁴-[2-(4-nitrophenyl)ethoxycarbonyl]cytidine ( 26 ), 2′-deoxy-N⁶-[2-(4-nitrophenyl)-ethoxycarbonyl]adenosine- 39 , and 2′-deoxy-N²-[2-(4-nitrophenyl)(ethoxycarbonyl]-O⁶-[2–4-nitrophenyl)ethyl]-guanosine ( 52 ) were further protected by the 2-(4-nitrophenyl)ethoxycarbonyl (npeoc) and the 2-(2,4-dinitrophenyl)ethoxycarbonyl (dnpeoc) group at the OH functions of the sugar moiety to form new partially and fully blocked intermediates for nucleoside and nucleotide syntheses. The corresponding 5′-O-monomethoxytrityl derivatives 5 , 18 , 30 , 40 , and 56 were also used as starting material to synthesize some other intermediates which were not obtained by direct acylations. In the ribonucleoside series, the 5′ -O-monomethoxytrityl derivatives 14 , 36 , 49 , and 63 reacted with 2-(4-nitrophenyl) ethyl chloroformate ( 1 ) to the corresponding 2′,3′-bis-carbonates 15 , 37 , 50 , and 64 which were either detriylated to 16 , 38 , 51 , and 65 , respectively, or converted by 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) treatment to the 2′,3′-cyclic carbonates 66 – 69 . The newly synthesized compounds were characterized by elemental analyses and UV and ¹H-NMR spectra.     

Preparation and Structure of (E)-1-(3′-Hydroxy-2-Furanyl)-3-(3″-Hydroxy-4″-Methoxyphenyl)-2-Propen-1-One

Abstract

A facile procedure is presented for the synthesis of (E)-1-(3′-hydroxy-2′-furanyl)-3-(3″-hydroxy-4″-methoxyphenyl)-2- propen-1-one (6). Galactosylisomaltol (1) was condensed with isovanillin (2) under strong alkaline conditions at 25 [ddot]C to form (E)-1-(3′-O-β-D-galactopyranosyloxy-2′-furanyl)-3-(3″- hydroxy-4″-methoxyphenyl)-2-propen-1-one (4). (E)-1-(3′-hydroxy-2′-furanyl)-3-(3″-hydroxy-4″-methoxyphenyl)-2-propen-1-one (6) was obtained by acid hydrolysis of 4 in a 53.9% yield. This hetero-cyclic 2-propen-1-one was characterized on the basis of spectral data (IR and ¹H NMR), physicochemical properties, and conversion to a mono-O-acetyl derivative.     

Regioselective Transformations of 2′,3′-Seconucleosides into Anhydro Structures and Chiral Crown Ethers

Intramolecular cyclisation of properly protected and activated derivatives of 2′,3′-secouridine ( = 1-{2-hydroxy-1-[2-hydroxy-1-(hydroxymethyl)ethoxy]-ethyl}uracil; 1 ) provided access to the 2,2′-, 2,3′-, 2,5′-, 2′,5′-, 3′,5′-, and 2′,3′-anhydro-2′,3′-secouridines 5, 16, 17, 26, 28 , and 31 , respectively (Schemes 1–3). Reaction of 2′,5′-anhydro-3′-O-(methylsulfonyl)- ( 25 ) and 2′,3′-anhydro-5′-O-(methylsulfonyl)-2′,3′-secouridine ( 32 ) with CH₂CI₂ in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene generated the N(3)-methylene-bridged bis-uridine structure 37 and 36 , respectively (Scheme 3). Novel chiral 18-crown-6 ethers 40 and 44 , containing a hydroxymethyl and a uracil-1-yl or adenin-9-yl as the pendant groups in a 1,3-cis relationship, were synthesized from 5′-O-(triphenylmethyl)-2′,3′-secouridine ( 2 ) and 5′-O,N⁶-bis(triphenylmethyl)-2′,3′-secoadenosine ( 41 ) on reaction with 3,6,9-trioxaundecane-1,11-diyl bis(4-toluenesulfonate) and detritylation of the thus obtained (triphenylmethoxy) methylcompound 39 and 43 , respectively (Scheme 4).     

Dispersed Fluorescence Spectroscopy and Transition Dipole Moment of HCO β 2A′-X̄2A′

Dispersed fluorescence spectra of β ²A′ - x? ²A′ transitions are measured on exciting HCO to the vibrational levels (0,0,0), (0,0,1), (0,1,0) and (1,0,0) of β ²A′ in a gas cell. Vibrational energies of bound and resonant states are determined for energy up to 17 500 cm^?1 from the ground vibrational level of the x? ²A′ state. Rotationally resolved spectra of the bands β ²A′ - x? ²A′ 2⁰₃3⁰₁, 2¹₄ and 2⁰₂3¹₂ were recorded and analyzed. Abnormal intensities in the P, Q and R branches are due to the mechanism of “axis switching”. From the ratios of emission intensity of a- and b-type transitions, without taking into account the varied lifetimes of rotational states of the upper electronic state, the directions of transition dipole moments of these bands are determined to be 39 ? 43° to the inertial a axis.     

Temperature dependence of the rate constants of the reactions of oxygen atoms with 1-pentene, 1-hexene,cis-2-pentene,and trans-2-pentene

The kinetics of the reactions of ground state oxygen atoms with 1-pentene, 1-hexene, cis-2-pentene, and trans-2-pentene was investigated in the temperature range 200 to 370 K. In this range the temperature dependences of the rate constants can be represented by k = A′ Tⁿ exp(− E′_a/RT) with A′ = (1.0 ± 0.6) · 10⁻¹⁴ cm³ s⁻¹, n = 1.13 ± 0.02, E′_a = 0.54 ± 0.05 kJ mol⁻¹ for 1-pentene: A′ = (1.3 ± 1.2) · 10⁻¹⁴ cm³ s⁻¹, n = 1.04 ± 0.08, E′_a = 0.2 ± 0.4 kJ mol⁻¹ for 1-hexene; A′ = (0.6 ± 0.6) · 10⁻¹⁴ cm³ s⁻¹, n = 1.12 ± 0.05, E′_a = − 3.8 ± 0.8 kJ mol⁻¹ for cis-2-pentene; and A′ = (0.6 ± 0.8) · 10⁻¹⁴ cm³ s⁻¹, n = 1.14 ± 0.06, E′_a = − 4.3 ± 0.5 kJ mol⁻¹ for trans-2-pentene. The atoms were generated by the H₂-laser photolysis of NO and detected by time resolved chemiluminescence in the presence of NO. The concentrations of the O(³P) atoms were kept so low that secondary reactions with products are unimportant. © 1997 John Wiley & Sons, Inc.     

Studies in spiroheterocycles,Part XV. Investigation of the reaction of 3-(2-oxocycloalkylidene)-indol-2-ones with thiourea and urea derivatives

The reaction of 3-(2-oxocycloalkylidene)indol-2-one 1 with thiourea and urea derivatives has been investigated. Reaction of 1 with thiourea and urea in ethanolic potassium hydroxide media leads to the formation of spiro-2-indolinones 2a-f in 40–50% yield and a novel tetracyclic ring system 4,5-cycloalkyl-1,3-diazepino-[4,5-b]indole-2-thione/one 3a-f in 30–35% yield. 3-(2-Oxocyclopentylidene)indol-2-one afforded 5′,6′-cyclopenta-2′-thioxo/ oxospiro[3H-indole-3,4′(3′H)pyrimidin]-2(1H)-ones 2a,b and 3-(2-oxocyclohexylidene)indol-2-one gave 2′,4′a,5′,6′,7′,8′- hexahydro-2′-thioxo/oxospiro[3H-indole-3,4′ (3′H)-quinazolin]-2(1H)-ones 2c-f . Under exactly similar conditions, reaction of 1 with fluorinated phenylthiourea/cyclohexylthiourea/phenylurea gave exclusively spiro products 2g-1 in 60–75% yield. The products have been characterized by elemental analyses, ir pmr. ¹⁹F nmr and mass spectral studies.     

Photochemische Reaktionen. 118. Mitteilung [1] Zur vinylogen β-Spaltung von Enonen. UV.-Bestrahlung von 4-(3',7',7'-Trimethyl-2'-oxabicyclo [3.2.0]hept-3'-en-1'-yl)but-3-en-2-on

Vinylogous β-Cleavage of Enones: UV.-irradiation of 4-(3′,7′,7′-trimethyl-2′-oxabicyclo[3.2.0]hept-3′-ene-1′-yl)but-3-ene-2-on On ¹π,π*-excitation (λ = 254 nm) in acetonitrile (E/Z)- 2 is converted into the isomers 4–9 and undergoes fragmentation yielding 10 ; in methanol (E/Z)- 2 gives 7–10 and is transformed into 11 by incorporation of the solvent. On ¹π,π*-excitation (λ λ?347 nm; benzene-d₆) (E)- 2 is isomerized into (Z)- 2 , which is converted into the isomers 3 and 4 by further irradiation. ¹π,π*-Excitation (λ = 254 nm; acetonitrile) of 4 gives 6 and (E)- 9 , whereas UV.-irradiation (λ = 254 nm; acetonitrile-d₃) of 5 yields (E)- 7 and 8 . On ¹π,π*-excitation (λ = 254 nm; acetonitrile) of (E/Z)- 12 the compounds (E)- 14 and (E)- 15 are obtained.     

Synthesis of 8-Aza-2′-deoxyadenosine and related 7-Amino-3H-1,2,3-triazolo[4,5-d]pyrimidine 2′-Deoxyribofuranosides: Stereoselective glycosylation via the nucleobase anion

The synthesis of 8-aza-2′-deoxyadenosine ( = 7-amino-3H-1,2,3 triazolo[4,5-d]pyrimidine N³-(2′-deoxy-β-D-ribofuranoside); 1 ) as well as the N²- and N¹-(2′-deoxy-β-D-ribofuranosides) 2 and 3 is described. Glycosylation of the anion of 7-amino-3H-1,2,3-triazolo[4,5-d]pyrimidine ( 6 ) in DMF yielded three regioisomeric protected 2′-deoxy-β-D-ribofuranosides, i.e. the N³-, N²-, and N⁴-glycosylated isomers 7 (14%), 9 (11%), and 11 (3%), respectively, together with nearly equal amounts of their α-D-anomers 8 (13%), 10 (12%), and 12 (4%; Scheme 1). The reaction became Stereoselective for the β-D-nucleosides if the anion of 7-methoxy-3H-1,2,3-triazolo[4,5-d]pyrimidine ( 13 ) was glycosylated in MeCN: only the N³-, N², and N¹-(2′-deoxy-β-D-nucleosides) 14 (29%), 15 (32%), and 16 (23%), respectively, were formed (Scheme 2). NH₃ Treatment of the methoxynucleosides 14–16 afforded the aminonucleosides 1–3 . The anomeric configuration as well as the position of glycosylation were determined by combination of ¹³ C-NMR , ¹ H-NMR , and 1D-NOE difference spectroscopy. Compound 1 proved to be a substrate for adenosine deaminase, whereas the regioisomers 2 and 3 were not deaminated.     

Reaction of N1,N2-diarylacetamidines with (2,4,7-trinitro-9H-fluoren-9-ylidene)propanedinitriles

Novel spiro[fluorene-9,4′-(1′,2′,3′,4′-tetrahydropyridine)]-5′-carbonitriles 6a-c have been obtained from the reaction of N¹,N²-diarylacetamidines 1a-c with (2,4,7-trinitro-9H-fluoren-9-ylidene)propanedinitrile ( 2 ) in ethyl acetate solutions at ambient temperature for 6a,b or under reflux for 6c , respectively.     

Mechanismus der photochemischen Methanol-Addition an 2-allylierte Aniline

Mechanism of the Photochemical Addition of Methanol to 2-Allylated Anilines We studied in methanol the photoreaction of the 2-allylated anilines, given in Scheme 3 (cf. also [ 1 ]). Irradiation of N-methyl-2-(1′-methylallyl)aniline ( 15 ) with a high pressure mercury lamp yielded trans- and cis-1,2,3-trimethylindoline (trans- and (cis- 34 ) as well as erythro- and threo-2-(2′-methoxy-1′-methylpropyl)-N-methylaniline (erythro- and threo- 35 ; Scheme 7). When the corresponding aniline d₃- 15 , specifically deuterated in the 1′-methyl group, was irradiated in methanol, a mixture of trans- and cis-d₃- 34 , and of erythro- and threo-d₃- 35 was obtained. Successive dehydrogenation of the mixture of cis/trans-d₃- 34 by Pd/C in boiling xylene and by MnO₂ in boiling benzene lead to the corresponding indole d₃- 36 (cf. Scheme 9), the ¹H- and ²H-NMR. spectra of which showed that both cis-d₃- and trans-d₃- 34 had bound the deuterium labeled methyl group exclusively at C(3). The ¹H- and ²H-NMR. analyses of the separated methanol addition products revealed that erythro-d₃- 35 contained the deuterium label to at least 95% in the methyl group at C(1′), and threo-d₃- 35 to 50% in CH₃? C(1′) and to 50% in CH₃? C(2′) (cf. Scheme 9). To confirm these results 2-(1′-ethylallyl)aniline ( 16 ) was irradiated in methanol, whereby a complex mixture of at least 6 products was obtained (cf. Scheme 11). Two products were identified as trans- and cis-3-ethyl-2-methylindoline (trans- and cis- 37 ). The four other products represented erythro- and threo-2-(1′-ethyl-2′-methoxypropyl)aniline (erythro- and threo- 39 ) as major components, and erythro- and threo-2-(2′-methoxy-1′-methylbutyl)aniline (erythro- and threo- 40 ). These results clearly demonstrate that the methanol addition products must arise from spirodienimine intermediates of the type of trans- 9 and cis- 11 (R¹ = CD₃ or C₂H₅, R² = CH₃ or H; Scheme 2) which are opened solvolytically with inversion of configuration by methanol. Thus, cis- 11 (R¹ = CD₃, R² = CH₃) must lead to a 1:1 mixture of threo- 13 and threo- 14 (i.e.) a 1:1 distribution of the deuterium labelled methyl group between C(1′) and C(2′) in threo- 35 ) The formation of erythro-d₃- 35 with at least 95% of the deuterium label in the methyl group at C(1′) indicates that trans- 9 (R¹ = CD₃, R² = CH₃) reacts with methanol regioselectively (> 95%) at the C(2), C(3) bond. Similarly, the formation of the methanol addition products in the photoreaction of 16 (Scheme 11) can be explained. Since the indolines, formed in both photoreactions, show no alteration in the position of the subsituent at C(1′) with respect to the starting material we suppose that the diradical 7 (R¹ = CD₃ or C₂H₅, R² = CH₃ or H; Scheme 2) is a common intermediate which undergoes competetive 1.3 and 1.5 ring closure yielding the spirodienimines and the indolines. This conception is supported by irradiation experiments with N, 3,5-trimethyl-2-(1′-methylally)aniline ( 17 ) and 2-(2′-cyclohexenyl)-N-methylaniline ( 18 ) in methanol. In the former case the formation of spirodienimines is hindered by the methyl group at C(3) for steric reasons, thus leading to a ratio of the indoline to the methoxy compounds of about 6.3 as compared with ca. 1.0 for 15 (cf. Scheme 12). On the other hand, no methoxy compounds could be detected in the reaction mixture of 18 (cf. Scheme 13) which indicates that in this case the 1.3 ring closure cannot compete with the 1.5 cyclization in the corresponding cyclic diradical of the type 7 (R¹–C(1′)–C(2′) is part of a six-membered ring; Scheme 2). We suppose that the diradicals of type 7 are formed by proton transfer in an intramolecular electron-donor-acceptor (EDA) complex arising from the excited single state of the aniline chromophor and the allylic side chain. This idea is supported by the fluorescence specta of 2-allylated N-methylanilines (cf. Fig.1-4) which show pronounced differences with respect to the corresponding 2-alkylated anilines. Furthermore, the anilines 18 and 20 when irradiated in methanol in the presence of an excess of trans-1,3-pentadiene undergo preferentially an intermolecular addition to the diene, thus yielding the N-(1′-methyl-2′-butenyl)anilines 52 and 51 , respectively (Scheme 15), i.e. as one would expect the diene with its low lying LUMO is a better partner for an EDA complex than the double bond of the allylic side chain.     

3-Deaza-2′-deoxyadenosine: Synthesis via 4-(methylthio)-1H-imidazo[4,5-c]pyridine 2′-deoxyribonucleosides and properties of oligonucleotides

The synthesis of 4-(methylthio)-1H-imidazo[4,5-c]pyridine 2′-deoxy-β-D -ribonucleosides 2 and 9 and the conversion of the N¹-isomer 2 into the 2′,3′-didehydro-2′,3′-dideoxyribonucleoside 3a or (via 7 ) 3-deaza-2′-deoxyadenosine ( 1 ) is described. Phosphonate building blocks of 1 were employed in solid-phase synthesis of self-complementary base-modified oligonucleotides. Their properties were studied with regard to duplex stability and hydrolysis by the restriction enzyme Eco RI.     

Synthesis of novel C-2 substituted pyrimidine nucleoside analogs

A series of 2-(2-oxoalkylidene)-4(1H)-pyrimidinone nucleoside analogs were synthesized by the addition of the lithium enolates of methylketones to 2,5′- and 2,2′-anhydrouridines and to 2,5′-anhydrothymidines. Alternatively, 2-thiouridine was alkylated with bromomethyl ketones to yield 2-(2-oxoalkyl)thio-4(1H)-pyrimidinone ribofuranosides in good yields. These intermediates were subsequently transformed into the title compounds via an Eschenmoser sulfur extrusion reaction. The 2-(2-oxoalkylidene)-4-(1H)-pyrimidinone nucleoside analogs exhibit enol proton signals in their ¹H nmr spectra indicative of hydrogen bonding between N-3 and keto oxygen. These structures offer functional groups with potential for Watson-Crick hydrogen bonding.     

Stereoselective Synthesis of Indazole 2′-Deoxy-β-D-ribonucleosides: Glycosylation of the Nucleobase Anion

The glycosylation of indazolyl anions derived from 4a , b with 2-deoxy-3,5-bis-O-(4-methylbenzoyl)-α-D -erythro-pentofuranosyl chloride ( 5 ) is described. The reaction was Stereoselective – exclusive β-D -anomer formation – but regioisomeric N¹- and N²-(2′-deoxy-β-D -ribofuranosides) (i.e. 6a and 7a , resp., and 6b and 7b , resp.) were formed in about equal amounts. They were deprotected to yield 8a , b and 9a , b . Compound 1 , related to 2′-deoxyadenosine ( 3 ), and its regioisomer 2 were obtained from 8b and 9b , respectively, by catalytic hydrogenation. The anomeric configuration as well as the position of glycosylation were determined by 1D NOE-difference spectroscopy. The first protonation site of 1 and 2 was found to be the NH₂ group. The N-glycosylic bond of 1H-indazole N¹-(2′-deoxyribofuranosides) is more stable than that of the parent purine nucleosides. Compound 1 is no substrate for adenosine deaminase.     

Lanthanide Complexes of Polyacid Ligands derived from 2, 6-bis(pyrazol-1-yl)pyridine,pyrazine, and 6, 6′-bis(pyrazol-1-yl)-2, 2′-bipyridine: Synthesis and luminescence properties

The synthesis of three novel pyrazole-containing complexing acids, N,N,N′,N′-{2, 6-bis[3-(aminomethyl)pyrazol-1-yl]-4-methoxypyridine}tetrakis(acetic acid)( 1 ), N,N,N′,N′-{2, 6-bis[3-(aminomethyl)pyrazol-1-yl]pyrazine}-tetrakis(acetic acid) ( 2 ), and N,N,N′,N′-{6, 6′-bis[3-(aminomethyl)pyrazol-1-yl]-2, 2′-bipyridine}tetrakis(acetic acid) ( 3 ) is described. Ligands 1–3 formed stable complexes with Eu^III, Tb^III, Sm^III, and Dy^III in H₂O whose relative luminescence yields, triplet-state energies, and emission decay lifetimes were measured. The number of H₂O molecules in the first coordination sphere of the lanthanide ion were also determined. Comparison of data from the Eu^III and Tb^III complexes of 1–3 and those of the parent trisheterocycle N,N,N′,N′-{2, 6-bis[3-(aminomethyl)pyrazol-l-yl]pyridine}tetrakis(acetic acid) showed that the modification of the pyridine ring for pyrazine or 2, 2′-bipyridine strongly modify the luminescence properties of the complexes. MeO Substitution at C(4) of 1 maintain the excellent properties described for the parent compound and give an additional functional group that will serve for attaching the label to biomolecules in bioaffinity applications.     

The conformation of t-butyl 2-methoxy-5, 6-dihydro-2 H-pyran-6-carboxylates and 6,6′- disubstituted 2-methoxy-5,6-dihydro-2H-pyran derivatives on the basis of 1H and 13 C NMR spectra

The ¹H and ¹³C NMR spectra of trans- and cis-tert-butyl 2-methoxy-5,6-dihydro-2H-pyran-6-carboxylates (1 and 2) and 6,6′-disubstituted 2-methoxy-5,6-dihydro-2H-pyrans (3-7) have been recorded. HH and CH coupling constants are discussed in terms of the ¹H₆?⁶H₁ conformational equilibrium. It has been found that 1 occurs exclusively in the ¹H₆ conformation, whereas its cis isomer, 2, exists in an equilibrium of both half-chair forms. 6,6′-Disubstituted 2-methoxy-5,6-dihydro-2H-pyrans 3-6 display spectral and conformational behaviour similar to that of 1, whereas 7 resembles 2 in this respect.