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.     

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.     

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.     

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.     

Facile Synthesis of 2′-Deoxyribofuranosides of Allopurinol and 4-Amino-1H-pyrazolo[3,4-d]pyrimidine via Phase-Transfer Glycosylation

Phase-transfer glycosylation of 4-methoxy-1H-pyrazolo[3,4-d]pyrimidine with the 2-deoxyribofuranosyl chloride 9 formed the N(1)-β-nucleoside 10a as main product (39%). As by-products the α-D -anomer 11a (7%) and the N(2)-isomer 12a (18%) were isolated. Assignment of these isomers was made on the basis of their ¹H- and ¹³C-NMR spectra. Removal of the sugar-protecting groups yielded the 4-methoxy-nucleosides 10b, 11b , and 12b , respectively. Nucleophilic displacement of the 4-MeO-group gave the 2-deoxyribofuranosides 1–4 of allopurinol and 4-amino-1H-pyrazolo[3,4-d]pyrimidine.     

TiO2 Nanoparticles Immobilized on Carbon Nanotubes: An Efficient Heterogeneous Catalyst in Cyclocondensation Reaction of Isatins with Malononitrile and 4-Hydroxycoumarin or 3,4-Methylenedioxyphenol under Mild Reaction Conditions

TiO₂ nanoparticles supported on carbon nanotubes (TiO₂-CNTs) as an efficient heterogeneous catalyst was used for the synthesis of spiro[3,4′]1,3-dihydro-2H-indol-2-one-2′-amino-5′-oxo-4'H,5'H-pyrano[3′,2′-c]chromen-3′-yl cyanides and spiro[3,8′]1,3-dihydro-2H-indol-2-one-6′-amino-8'H-[1′,3′]dioxolo[4′,5′-g]chromen-7′-yl cyanides via the cyclocondensation reaction of isatins with malononitrile and 4-hydroxycoumarin or 3,4-methylenedioxyphenol in aqueous media at room temperature. This reaction offers several sustainable and economic benefits such as high yields of products, convenient operation, and use of non-toxic catalyst in water media.     

Synthesis,crystal structure,and magnetic properties of a linear trinuclear Cu(II) complex

A new linear trinuclear Cu(II) complex, [Cu₃(NTA)₂(4,4′-bpt)₄(H₂O)₂]?·?10H₂O (H₃NTA?=?nitrilotriacetic acid, 4,4′-bpt?=?4-amino-3,5-bis(4-pyridyl)-1,2,4-triazole) (1), was obtained from evaporation of an aqueous solution containing Cu(NO₃)₂?·?6H₂O, 4,4′-bpt, nitrilotriacetic acid (H₃NTA), and NaOH. 1 was characterized using single-crystal X-ray diffraction, IR, and elemental analysis. In the trimer, the three linear copper ions are bridged by two NTA carboxylate groups in a syn–anti conformation and connected by 4,4′-bpt to produce a 1-D array. Temperature-dependent magnetic susceptibilities reveal the presence of weak antiferromagnetic exchange between metal centers.     

Solvothermal synthesis,structure, and luminescence of a 3-D Cd(II) complex assembled with biphenyl-2,5,2′,5′-tetracarboxylic acid involving in situ ligand reaction

A 3-D metal-organic framework [Cd₃(L)₂(DMF)₂]?·?2H₂O?·?2DMF (1) (H₃L?=?2-(dimethylcarbamoyl)biphenyl-5,2′,5′-tricarboxylic acid, DMF?=?N,N-dimethylformamide) with trinuclear Cd(II) units has been prepared. Complex 1 is a (3,?6)-connected (4²?·?6)₂(4⁴?·?6²?·?8⁸?·?10) coordination net, which results from the solvothermal in situ formation of a new asymmetric ligand, 2-(dimethylcarbamoyl)biphenyl-5,2′,5′-tricarboxylic acid (H₃L), through amidation of biphenyl-2,5,2′,5′-tetracarboxylic acid (H₄bptc). Additionally, the luminescence of 1 has been investigated.     

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 ).     

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 ).     

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.     

A Doubly Interpenetrated Cu(II)-based Metal-Organic Framework as a Heterogeneous Catalyst for the ipso-Hydroxylation of Arylboronic Acids

A doubly interpenetrated Cu(II)-organic framework with formula [{Cu₂( L )₂(4,4′-bpdc)₂(H₂O)₂} ⋅ 8H₂O ⋅ CH₃OH]_α ( 1 ) (where, L =N², N⁶-di(pyridin-4-yl)naphthalene-2,6-dicarboxamide and 4,4′-bpdc=[1,1′-biphenyl]-4,4′-dicarboxylate ion) has been synthesized and characterized with the help of several spectroscopic and analytical techniques including single crystal X-ray analysis. A single crystal X-ray analysis reveals that 1 exhibit interpenetrated two-dimensional sheet-like structure containing elongated channels of cross-section 11.09×31.22 Ų along the a-axis. Finally, 1 has been exploited as a heterogeneous catalyst for the ipso-hydroxylation of arylboronic acids yielding up to 99 % of the respective phenolic product. Importantly, the catalyst can be reused for five successive cycles without having a significant loss in its catalytic efficiency.     

2′-Deoxy-β-D-ribofuranosides of N6-Methylated 7-Deazaadenine and 8-Aza-7-deazaadenine: Solid-phase synthesis of oligodeoxyribonucleotides and properties of self-complementary duplexes

The syntheses of 7-deaza-N⁶-methyladenine N⁹-(2′-deoxy-β-D -ribofuranoside) ( 2 ) as well as of 8-aza-7-deaza-N⁶-methyladenine N⁸? and N⁹?(2′-deoxyribofuranosides) ( 3 and 4 , resp.) are described. A 4,4′-dimeth-oxylritylation followed by phosphitylation yielded the methyl phosphoramidites 12–14 . They were employed together with the phosphoramidite of 2′-deoxy-N⁶v-methyladenosine ( 15 ) in automated solid-phase oligonucleotide synthesis. Alternating or palindromic oligonucleotides derived from d(A-T)₆ or d(A-T-G-C-A-G-A*-T-C-T-G-C-A) but containing one methylated pyrrolo[2,3-d]pyrimidine or pyrazolo[3,4-d]pyrimidine moiety in place of a N⁶-methylaminopurine (A*) were synthesized. Melting experiments showed that duplex destabilization induced by a N⁶-Me group of 2′-deoxy-N⁶-methyladenosine is reversed by incorporation of 8-aza-7-deaza-2′-deoxy-N⁶-meihyladenosine, whereas 7-deaza-2′-deoxy-N⁶-methyladenostne decreased the T_m value further. Regiospecific phosphodiester hydrolysis of d(A-T-G-C-A-G-m⁶A-T-C-T-G1-C-A) by the endodeoxyribonuclease Dpn I, yielding d(A-T-G-C-A-G-m⁶A) and d(pT-C-T-G-C-A), was prevented when the residue c⁷m⁶A_d ( 2 ), c⁷m⁶z⁸A_d ( 3 ), or c⁷m⁶z⁸A_d′ ( 4 ) replaced m⁶A_d ( 1 ) indicating that N(7) of N⁶-methyladenine is a proton-acceptor site for the endodeoxyribonuclease.     

Different two-dimensional metal-organic frameworks through ligand modification

Through ligand modification, we have replaced the central benzene ring of H₂TDBA ([1,1′:3′,1″-terphenyl]-4,4″-dicarboxylic acid) with the pyridine structurally related ligand H₂PDDA (4,4′-(pyridine-2,6-diyl)dibenzoic acid), which makes the central pyridine ring of H₂PDDA more coplanar with two benzene rings on both sides of the ligand. The modification results in a dramatically different linkage configuration, thereby allowing structural changes to the metal-organic frameworks (MOFs). Two 2-D MOFs, [Cu(TDBA)(DMA)₂]·H₂O (BUT-221, DMA = N,N-dimethylacetamide), and [Cu₃(PDDA)₃(DMA)₂(H₂O)]·5H₂O (BUT-223) have been synthesized through reactions of two ditopic carboxylate ligands with Cu(NO₃)₂·3H₂O under solvothermal conditions, and characterized by single-crystal X-ray diffraction, powder X-ray diffraction, thermogravimetric analysis and infrared spectroscopy. Topological analysis shows that BUT-221 is a twofold parallel interpenetrating 4⁴ 2-D network with a skl topology, while BUT-223 is a 2-D network with a kgm topology.     

Two- and three-dimensional photoluminescent Cd(II)-carboxylate coordination frameworks bridged by benzenepentacarboxylate and N-donor ligands

Reactions of Cd(OAc)₂·H₂O, benzenepentacarboxylic acid (H₅bpc), 2,2′-bpy/4,4′-bpy, and Et₃N yield two new coordination polymers [Cd₅(bpc)₂(2,2′-bpy)₄(H₂O)₄] (1) and [Cd₅(bpc)₂(4,4′-bpy)₂(H₂O)₄]·3H₂O (2). Complex 1 is a 2-D structure based on six-connected Cd-carboxylate layers. Adjacent layers are linked by π–π interactions and hydrogen bonds to generate a layered supramolecular network. Complex 2 is a 3-D coordination framework. The bpc ligands adopting μ ₇-bridging mode connect Cd(II) ions to form a 3-D open framework with elliptic channels, in which the coordinated 4,4′-bpy ligands fill to support the whole framework. Complex 2 exhibits strong photoluminescence at room temperature.     

Syntheses,structures, and properties of four coordination compounds constructed from asymmetric semi-rigid V-shaped multicarboxylate ligand

Four new compounds, [Mn(HL)(phen)₂(H₂O)] (1), [Ni(HL)(phen)₂(H₂O)] (2), [Zn(HL)(4,4′-bipy)_1.5(H₂O)] _n ?·?2nH₂O (3) and [Zn₂(HL)₂(H₂O)₆] (4), have been synthesized from an asymmetric semi-rigid V-shaped multicarboxylate 4-(4-carboxy-phenoxy)-phthalic acid (H₃L) with 1,10-phenanthroline (phen), or 4,4′-bipyridine (4,4′-bipy) as auxiliary ligands. Single-crystal X-ray diffraction analysis reveals that 1, 2 and 4 have 0-D structures with 3-D supramolecular frameworks formed by intermolecular hydrogen bonds. Compound 3 shows a 1-D infinite ribbon bridged by 4,4′-bipy, which further forms a 3-D supramolecular architecture by π–π stacking interactions and hydrogen bonds. Thermal stabilities of 1–4 and luminescence properties of 3 and 4 have also been investigated.     

Über die Dicyanierung der 1,4-Diaminoanthrachinone und die Reaktivität der 1,4-Diamino-9,10-dihydroanthracen-2,3-dicarbonitrile gegenüber nucleophilen Reagenzien 3. Mitteilung über Arylierungen und Heterocyclisierungen von Anthrachinonsystemen

The Dicyanation of 1,4-Diaminoanthraquinones and the Reactivity of 1,4-Diamino-9,10-dioxo-9,10-dihydroanthracene-2,3-dicarbonitriles towards Nucleophilic Reagents The reaction of 1-amino-9, 10-dioxo-4-phenylamino-9,10-dihydroanthracene-2-sulfonic acid ( 1 , R?C₆H₅) with cyanide in water yields a mixture of 1-amino-9,10-dioxo-4-phenylamino-9,10-dihydroanthracene-2-carbonitrile ( 3 , R ? C₆H₅) and 1-amino-4-(phenylamino)anthraquinone ( 4 , R ? C₆H₅) under the usual reaction conditions (Scheme 1). In dimethylsulfoxide, however, a second cyano group is introduced, and 1-amino-9,10-dioxo-4-phenylamino-9,10-dihydroanthracene-2,3-dicarbonitrile (7) is formed (Scheme 2). The cyano groups are very reactive towards nucleophiles. The cyano group in 2-position can be substituted by hydroxide and aliphatic amines (Schemes 5 and 6). The cyano group in 3-position can be eliminated by aliphatic amines and hydrazine (Scheme 7). Nucleophilic attack at the cyano C-atom of the 2-cyano group by suitable reagents leads to ring formation, yielding e.g. 2-(Δ²-1, 3-oxazolin-2-yl)-, 2-(benz[d]imidazol-2-yl)- and 2-(1H-tetrazol-5-yl)anthraquinones (Schemes 8 and 10).     

Nucleoside und Nucleotide. Teil 10. Synthese von Thymidylyl-(3′-5′) -thymidylyl-(3′-5′)-1-(2′-desoxy-β-D-ribofuranosyl)-2(1 H)-pyridon

Nucleosides and Nucleotides. Part 10. Synthesis of Thymidylyl-(3′-5′)-thymidylyl-(3′-5′)-1-(2′-deoxy-β-D - ribofuranosyl)-2(1 H)-pyridone The synthesis of 5′-O-monomethoxytritylthymidylyl-(3′-5′)-thymidylyl-(3′-5′)-1-(2′-deoxy-β-D -ribofuranosyl)-2(1H)-pyridone ((MeOTr)T_dpT_dp∏_d, 5 ) and of thymidylyl-(3′-5′)-thymidylyl-(3′-5′)-1-(2′-deoxy-β-D -ribofuranosyl)-2(1 H)-pyridone (T_dpT_dp∏_d, 11 ) by condensing (MeOTr) T_dpT_d ( 3 ) and p∏_d(Ac) ( 4 ) in the presence of DCC in abs. pyridine is described. Condensation of (MeOTr) T_dpT_dp ( 6 ) with Π_d(Ac) ( 7 ) did not yield the desired product 5 because compound 6 formed the 3′-pyrophosphate. The removal of the acetyl- and p-methoxytrityl protecting group was effected by treatment with conc. ammonia solution at room temperature, and acetic acid/pyridine 7 : 3 at 100°, respectively. Enzymatic degradation of the trinucleoside diphosphate 11 with phosphodiesterase I and II yielded T_d, pT_d and p∏_d, T_dp and Π_d, respectively, in correct ratios.