2′‐Deoxyimmunosine: a thiazolo[4,5‐d]pyrimidine nucleoside adopting the syn conformation

The title compound [systematic name: 5‐amino‐3‐(2‐deoxy‐β‐d ‐erythro‐pentofuranosyl)thiazolo[4,5‐d]pyrimidine‐2,7‐(3H,6H)‐dione], C₁₀H₁₂N₄O₅S, exhibits a syn glycosylic bond conformation, with a torsion angle χ of 61.0 (3)°. The furanose moiety adopts the N‐type sugar pucker (³T₄), with P = 33.0 (5)° and τ_m = 15.1 (1)°. The conformation at the exocyclic C4′—C5′ bond is +ap (trans), with the torsion angle γ = 176.71 (14)°. The extended structure is a three‐dimensional hydrogen‐bond network involving O—H...O and N—H...O hydrogen bonds.     

New 1,2,3‐triazolo[4,5‐d]1,2,4‐triazolo[3,4‐b]pyridazine derivatives II

New tricyclic 1,2,3‐triazolo‐1,2,4‐triazolo‐pyridazine derivatives, bearing a methyl substituent on the 1,2,3‐triazole ring, were prepared as potential biological agents. N‐Methylation of dimethyl 1,2,3‐triazole‐4,5‐dicarboxylate allowed synthesis of the isomeric 1‐methyl‐4,7‐dihydroxy and 2‐methyl‐4,7‐dihydroxy triazolo‐pyridazines 4a and 4b which, by a chlorination reaction, gave the corresponding 1‐methyl‐4‐chloro‐( 6a ), 1‐methyl‐7‐chloro‐ ( 6b ) and 2‐methyl‐4‐chloro‐ ( 9 ) substituted 1,2,3‐triazolo‐pyridazines. The nucle‐ophilic substitution with hydrazine hydrate and the suitable cyclization to form the 1,2,4‐triazole ring, provided the expected tricyclic isomeric derivatives 8a, 8b and 11 respectively. The p‐methoxybenzyl substituent, introduced as a leaving group to obtain either v‐triazolo‐pyridazine or v‐triazolo‐s‐triazolo‐pyri‐dazine derivatives unsubstituted on the 1,2,3‐triazole ring, appeared inadequate. Some compounds underwent binding assays toward the adenosine A₁and A_2A receptors.     

New 1,2,3‐triazolo[4,5‐e]1,2,4‐triazolo[4,3‐c]pyrimidine derivatives II

The 7‐chloro‐3‐(2‐chlorobenzyl)‐ and 7‐chloro‐3‐(2‐fluorobenzyl)‐1,2,3‐triazolo[4,5‐d]pyrimidines ( 1 and 4 ), by nucleophilic replacement with some hydrazides, gave the corresponding 7‐hydrazidoderivatives ( 2a‐e and 5a‐e ). These, by heating in Dowtherm, underwent an intramolecular cyclization to form the new tricyclic 7‐substituted‐3‐(2‐chlorobenzyl)‐ and 3‐(2‐fluorobenzyl)‐1,2,3‐triazolo[4,5‐e]1,2,4‐triazolo[4,3‐c]pyrimidines ( 3a‐d and 6a‐d ). The 7‐hydrazino‐3‐(2‐chlorobenzyl)‐ and 7‐hydrazino‐3‐(2‐fluorobenzyl)‐triazolo‐pyrimidines ( 9a and 9b ) were also prepared via the corresponding mercapto ( 7a and 7b ) and thiomethyl ( 8a and 8b ) derivatives.     

Synthesis of 1‐substituted [1,2,3]triazolo[4,5‐d]pyridazines as precursors for novel tetraazapentalene derivatives

A series of 1‐substituted 4,5‐diformyl‐[1,2,3]triazole derivatives were prepared by 1,3‐dipolar cyclo‐addition of aryl azides with acetylene dicarboxaldehyde mono‐diethylacetal. The triazoles were readily converted into 1‐substituted [1,2,3]triazolo[4,5‐d]pyridazines in good yields. The 1‐(2‐nitrophenyl)‐[1,2,3]triazolo[4,5‐d]pyridazine was found to be a useful intermediate for the generation of the novel 5H‐benzo[1,2,3]triazolo[1′,2′:1,2]triazolo[4,5‐d]pyridazin‐6‐ium inner salt ring system.     

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 ).     

5‐Methyl­sulfanyl‐3H‐1,2,3‐triazolo[4,5‐d]pyrimidin‐7(6H)‐one (2‐methyl­thio‐8‐aza­xanthine) monohydrate

The title compound, C₅H₅N₅OS·H₂O, crystallizes as the monohydrate. Disorder of the H atoms that participate in the hydrogen bonds implies that two different tautomers are present in the crystal structure, one of them with both acidic H atoms attached to the imidazole ring and the other with one acidic H atom on each ring.     

An expedient synthesis of novel,fused pyrimido[4,5‐d]pyrimidine and pyrimido [5,4‐e] [1,2,4]triazolo[4,3‐c]pyrimidine analogues from 4‐amino‐2,6‐dichloro‐pyrimidine

A number of potent pyrimido[4,5‐d]pyrimidine have efficiently been synthesized by the condensation of 4‐amino‐2,6‐dichloropyrimidine with various substituted benzaldehyde followed by cyclization with ammonium thiocyanate. Also, these newly synthesized derivatives were utilized for the construction of novel pyrimido[5,4‐e][1,2,4]triazolo[4,3‐c]pyrimidine analogues via oxidative cyclization involving 1,5‐hydrogen abstraction. Structure of all the newly constructed derivatives was corroborated by the elemental and spectral data. © 2006 Wiley Periodicals, Inc. Heteroatom Chem 17:245–253, 2006; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20177     

3‐Bromo‐1‐(2‐deoxy‐β‐d‐erythro‐pento­furan­osyl)‐1H‐pyrazolo­[3,4‐d]­pyrimidine‐4,6‐di­amine: a nucleoside which strongly enhances DNA duplex stability

The title compound, C₁₀H₁₃BrN₆O₃, exhibits an anti gly­cosylic bond conformation, with an O—C—N—C torsion angle of −105.0 (6)°. The pseudorotation phase angle and the amplitude [P = 5.8 (5)° and τ_m = 30.0 (3)°, respectively] indicate N‐type sugar puckering (³T₂).     

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.     

Pyrrolo[3,4‐e][1,2,3]triazolo[1,5‐a]pyrimidine and pyrrolo[3,4‐d] [1,2,3]triazolo[1,5‐a]pyrimidine. New tricyclic ring systems of biological interest

Derivatives of the new ring system pyrrolo[3,4‐e][1,2,3] triazolo[1,5‐a]pyrimidine 6 were prepared in high yields in one step by reaction of 3‐azidopyrrole 3 and substituted acetonitriles. Compound 6b rearranged, upon heating in dimethyl sulfoxide in the presence of water, to pyrrolo[3,4‐d][1,2,3]triazolo‐[1,5‐a]pyrimidine 7.     

Synthesis and Antimicrobial Screening of Some Novel 2‐(5‐(4‐(1H‐Benzo[d][1,2,3]triazol‐1‐yl)phenyl)‐4,5‐dihydro‐1H‐pyrazol‐3‐yl)phenols Incorporated by Triazole Moiety

A novel series of 2‐(5‐(4‐(1H‐benzo[d][1,2,3]triazol‐1‐yl)phenyl)‐4,5‐dihydro‐1H‐pyrazol‐3‐yl)phenols derivative has been synthesized from (E)‐3‐(4‐(1H‐benzo[d][1,2,3]triazol‐1‐yl)phenyl)‐1‐(2‐hydroxyphenyl)prop‐2‐en‐1‐ones in ethanol and hydrazine hydrate under reflux condition. The synthesized compounds were screened for antibacterial activity against Gram‐positive bacteria viz Staphylococcus aureus and Bacillus subtilis and Gram‐negative bacteria viz Escherichia coli and Salmonella typhi, respectively. Some of the tested compounds showed significant antimicrobial activity. IR, ¹H NMR, mass spectral data, and elemental analysis elucidated the structures of all the newly synthesized compounds.     

New access to thiazolo[4,5‐d]pyrimidine derivativess

4‐Amino‐5‐bromo‐2‐substituted‐aminopyrimidines are readily obtained from the newly prepared 5‐bromo‐2,4‐dichloro‐6‐methylpyrimidine by sequential treatment with ethanolic ammonia and secondary amines. These compounds were successfully reacted with various isothiocyanates in the presence of sodamide in DMF to form the new thiazolo[4,5‐d] pyrimidine derivatives.     

1,7‐Dideaza‐2′‐deoxy‐6‐nitronebularine: a pyrrolo[2,3‐b]pyridine nucleoside with an intramolecular hydrogen bond stabilizing the syn conformation

The title compound [systematic name: 1‐(2‐deoxy‐β‐D‐erythro‐pentofuranosyl)‐4‐nitro‐1H‐pyrrolo[2,3‐b]pyridine], C₁₂H₁₃N₃O₅, forms an intramolecular hydrogen bond between the pyridine N atom as acceptor and the 5′‐hydroxy group of the sugar residue as donor. Consequently, the N‐glycosylic bond exhibits a syn conformation, with a χ torsion angle of 61.6 (2)°, and the pentofuranosyl residue adopts a C2′‐endo envelope conformation (²E, S‐type), with P = 162.1 (1)° and τ_m = 36.2 (1)°. The orientation of the exocyclic C4′—C5′ bond is +sc (gauche, gauche), with a torsion angle γ = 49.1 (2)°. The title nucleoside forms an ordered and stacked three‐dimensional network. The pyrrole ring of one layer faces the pyridine ring of an adjacent layer. Additionally, intermolecular O—H...O and C—H...O hydrogen bonds stabilize the crystal structure.     

The regioisomeric 1H(2H)‐pyrazolo[3,4‐d]pyrimidine N1‐ and N2‐(2′‐deoxy‐β‐D‐ribofuranosides)

In the title regioisomeric nucleosides, alternatively called 1‐(2‐deoxy‐β‐d ‐erythro‐furan­osyl)‐1H‐pyrazolo­[3,4‐d]­pyrimidine, C₁₀H₁₂N₄O₃, (II), and 2‐(2‐deoxy‐β‐d ‐erythro‐furan­osyl)‐2H‐pyrazolo­[3,4‐d]pyrimidine, C₁₀H₁₂N₄O₃, (III), the conformations of the gly­cosyl­ic bonds are anti [?100.4 (2)° for (II) and 15.0 (2)° for (III)]. Both nucleosides adopt an S‐type sugar pucker, which is C2′‐endo‐C3′‐exo (²T₃) for (II) and 3′‐exo (between ₃E and ⁴T₃) for (III).     

Synthesis and tautomerization of 6,7‐dihydro‐(1,2,3)‐triazolo[1,5‐a]pyrimidines

The condensation of 5‐amino‐4‐phenyl‐1,2,3‐triazole ( 1 ) with chalcones 2a‐e or 3‐dimethylamino‐propiophenone ( 4f ) leads to the 6,7‐dihydro‐(1,2,3)‐triazolo[1,5‐a]pyrimidines 3a‐f. The equilibrium of 3 and the tautomeric 4,7‐dihydro‐(1,2,3)‐triazolo[1,5‐a]pyrimidines 3′ is described.     

The crystal structure of 9‐chloro‐4,5‐dihydro‐2‐ethyl‐1‐(2,4,6‐trichlorophenyl)‐1H‐1,2,4‐triazolo[3,2‐d][1,5]‐benzoxazepinium hexachloroantimonate

The title compound 4 , i.e. 9‐chloro‐4,5‐dihydro‐2‐ethyl‐1‐(2,4,6‐trichlorophenyl)‐1H‐1,2,4‐triazolo[3,2‐d]‐[1,5]benzoxazepinium hexachloroantimonate, is a novel 6‐7‐5 tricyclic heterocycle. C₁₈H₁₄Cl₄N₃O·SbCJ₆, M = 764.61, P2₁/c(#14), a = 13.457(4), b = 11.583(2), c = 18.992(3) Å α = 90, β = 110.11(1)°, Z = 4, V = 2780(1) ų, D_c = 1.827 g/cc, μ (MoKα) = 19.69 cm^?1, F(000) = 1488.00, T = 293 K, R_int = 0.055 for 3094 independent reflections with I>3.00σ(I). The five‐membered heterocyclic ring is nearly planar, with the trichlorophenyl ring at N(2) almost perpendicular to it. However, the seven‐membered ring is not planar, but adopts a twist‐boat conformation.     

4‐Amino‐7‐(2‐de­oxy‐2‐fluoro‐β‐d‐arabinofuranos­yl)‐5‐fluoro‐7H‐pyrrolo[2,3‐d]pyrimidine: a bis‐fluorinated analogue of 2′‐deoxy­tubercidin

The title compound, C₁₁H₁₂F₂N₄O₃, exhibits an anti glycosylic bond conformation, with a torsion angle χ = −117.8 (2)°. The sugar pucker is N‐type (C4′‐exo, between ³T₄ and E₄, with P = 45.3° and τ_m = 41.3°). The conformation around the exocyclic C—C bond is −ap (trans), with a torsion angle γ = −177.46 (15)°. The nucleobases are stacked head‐to‐head. The crystal structure is characterized by a three‐dimensional hydrogen‐bond network involving N—H⋯O, O—H⋯O and O—H⋯N hydrogen bonds.     

Synthesis of Novel Fluorescent 2‐{4‐[1‐(Pyridine‐2‐yl)‐1H‐pyrazol‐3‐yl] phenyl}‐2H‐naphtho [1,2‐d] [1,2,3] triazolyl Derivatives and Evaluation of Their Thermal and Photophysical Properties

Novel 2‐{4‐[1‐(pyridine‐2‐yl)‐1H‐pyrazol‐3‐yl] phenyl}‐2H‐naphtho [1,2‐d] [1,2,3] triazolyl fluorescent derivatives were synthesized from p‐nitrophenylacetic acid and 2‐hydrazino pyridine through Vilsmeier–Haack and diazotization reactions. Photophysical properties were evaluated, and results show that compounds have good fluorescence quantum yields. Thermal analysis showed that they are reasonably stable. The structures of the compounds were confirmed by FT‐IR, ¹H NMR, ¹³C NMR, and mass spectral and elemental analysis.