NMR investigation and theoretical studies on the tautomerism of β,β′-tricarbonyl compounds

The behaviour on keto–enol tautomeric equilibration of ethyl 2-benzoyl-5-(2-furyl)-3-hydroxy-penta-2,4-dienoate (1) and ethyl 2-acetyl-3-hydroxy-5-phenyl-penta-2,4-dienoate (2) was investigated by ¹H and ¹³C NMR spectroscopy in different solvents and BP86/TZVP density functional theory computations. The spectral assignment to enol and keto tautomers was performed with one- and two-dimensional techniques. The percentage of the keto form in the tautomeric equilibrium depends on solvents and rises by increasing solvent polarity. The enol–enol tautomerism is also discussed on the basis of the coupling constants ²J_C,OH, ³J_C,OH and ⁴J_H,OH, respectively.     

Metal catalysed reactions of β,β′-tricarbonyl derivatives with isocyanates

The reactions of β,β′-tricarbonyl derivatives with isocyanates are catalysed by 2 mol % transition metal acetylacetonates (e.g., [Co(acac)₂] and [Zn(acac)₂]) at room temperature. 3-Oxo-1,5-pentanedioic acid dimethylester (1) reacts with RNCO (R=Et, CH₂CHCH₂, CH₂Ph, Ph, 4-Cl-Ph) to give 1:1 adducts involving the formation of a new C-C bond between the intercarbonylic methylene and the isocyanato group. Under similar conditions 2,4,6-heptanetrione (2) reacts with the same isocyanates to afford pyridinone and pyranone derivatives resulting from the cyclisation of unstable 1:1 and 1:2 adducts.     

Synthesis and properties of siRNAs containing 5′-amino-2′,5′-dideoxy-2′α-fluororibonucleosides

Short interfering RNAs (siRNAs) containing P3′→N5′ phosphoramidate linkages were successfully synthesized by introducing 2′-deoxy-2′-fluororibonucleoside and 5′-amino-2′,5′-dideoxy-2′α-fluororibonucleoside in succession. It was found that the introduction of 5′-amino-2′,5′-dideoxy-2′α-fluororibonucleosides into siRNAs improved the nuclease-resistant properties of the siRNAs without loss of their silencing efficacy.     

Regioselective [3+4] cycloaddition of an azomethine ylide to meso-meso, β-β, β′-β′ triply linked diporphyrins

Thermal reaction of meso-meso, β-β, β′-β′ triply linked diporphyrins with an azomethine ylide produced seven-membered cycloadducts via formal [3+4] cycloaddition at the bay-area. Bischlorin structures of the cycloadducts are characterized on the basis of spectroscopic data and confirmed by single crystal X-ray diffraction analysis. Interestingly, the stability of the cycloadducts depends on the central metal ions in the porphyrin core.     

Efficient synthesis of 3-cyanovinylcarbazole-1′-β-deoxyriboside-5′-triphosphate: a reversible photo-cross-linking probe

We describe an efficient synthesis of 3-cyanovinylcarbazole-1′-β-deoxyriboside-5′-triphosphate containing light-responsive artificial nucleobase 3-cyanovinylcarbazole, which can be used as a reversible photo-cross-linking probe with nucleic acid compounds for various biological applications. A three-step synthesis of 3-cyanovinylcarbazole-1′-β-deoxyriboside starting from 3-cyanovinylcarbazole, followed by ‘one-pot, three-step’ procedure is presented to accomplish the title compound 3-cyanovinylcarbazole-1′-β-deoxyriboside-5′-triphosphate in good yields.     

Synthesis and anti-HIV activity of l-β-3′-C-cyano-2′,3′-unsaturated nucleosides and l-3′-C-cyano-3′-deoxyribonucleosides

An efficient synthetic method was developed for l-β-3′-C-cyano-2′,3′-unsaturated nucleosides and l-3′-C-cyano-3′-deoxyribonucleosides. The key intermediate 11 was obtained from l-xylose, from which a series of pyrimidine and purine nucleosides were prepared in high yield by the coupling of 11 and various silyl-protected bases in the presence of TMSOTf. These nucleosides were eliminated, followed by deprotecting to give l-β-3′-C-cyano-2′,3′-unsaturated nucleosides. When selectively deprotected by hydrazine hydrate in buffered acetic acid-pyridine followed by treatment with potassium carbonate in methanol, l-3′-C-cyano-3′-deoxyribonucleosides were obtained. The synthesized nucleosides were tested for anti-HIV activity.     

5,5′-二甲基-2,2′-二茚满-1,1′,3,3′-四酮的合成及结构表征

本文以4-甲基邻苯二甲酸酐为原料, 成功地合成了5,5′-二甲基-2,2′-二茚满-1,1′,3,3′-四酮(2). 通过元素分析、核磁共振、红外光谱及质谱等测试手段, 确定了化合物2的结构与存在形式, 通过ESR测试发现化合物2具有顺磁性.     

Unusual β,β′-coupling and β-alkylation of methyl 2,3,3-trifluoropropenoate by lithium diorganocuprates

Methyl 2,3,3-trifluoroprop-2-enoate (1) reacts with lithium diorganocuprates in two ways, by fluorine substitution at C-3 with alkyl or aryl, or by β,β′ C,C-coupling. The reaction product was strongly dependent on the organyl structure: while dibutyl- or diphenylcuprate reacted by C-3 substitution, dimethylcuprate afforded the product of the coupling, dimethyl (Z,Z)-2,3,4,5-tetrafluorohexa-2,4-dienedioate (3). (Z)-Configuration is highly prevailing in 3-alkylated 2,3-difluoropropenoates (77-90% rel.).     

一种5,5′,6,6′-四氯-1,1′-3,3′-四乙基苯并咪唑羰花青碘化物的合成方法

JC-1作为一种荧光探针,广泛应用于线粒体细胞膜的电位测定。本文以1,2,4-三氯-5-硝基苯为起始底物,经多步反应以18%的总收率获得JC-1。     

Highly stereoselective synthesis of 2′-deoxy-β-ribonucleosides via a 3′-(N-acetyl)-glycyl-directing group

A facile synthesis of 2′-deoxy-β-ribonucleosides from 3′-O-(N-acetyl)-glycyl-protected 2′-deoxyribofuranose has been developed. The coupling reactions between the protected 2′-deoxyribose and silylated bases exhibited β-selectivity up to 98% presumably via a 1′,3′-participation mechanism. The 3′-directing group can be introduced and removed easily under mild conditions. This approach provides an efficient and highly stereoselective entry for the synthesis of 2′-deoxy-ribonucleosides.     

Efficient synthesis of nucleoside 5′-triphosphates and their β,γ-bridging oxygen-modified analogs from nucleoside 5′-phosphates

Thirteen nucleoside 5′-triphosphates (NTPs) and their β,γ-bridging oxygen-modified analogs (β,γ-CX₂-NTPs, X = H, F, Cl, and Br) have been efficiently synthesized from nucleoside 5′-phosphoropiperidates with 4,5-dicyanoimidazole as the activator. A high-yielding and chromatography-free protocol for the preparation of both natural and base-modified nucleoside 5′-phosphoropiperidates from the corresponding nucleoside 5′-phosphates was also developed.     

Synthesis of 2′-β-C-methyl-neplanocin derivatives as anti-HCV agents

The synthesis of 2′-β-C-methyl-neplanocin derivatives is described. The key intermediate cyclopentenyl alcohol 12 is prepared from sugar 5 in 12 steps. Coupling of 12 with appropriately protected purine, 7-deaza pyrimidine, uracil and pyrimidine bases via the Mitsunobu reaction followed by deprotection afforded the target cyclopentenyl nucleosides (18-23, 27). The synthesized compounds were evaluated as potential inhibitors of the hepatitis C virus (HCV) in vitro. Unfortunately, none of them show anti-HCV activity below EC₅₀ 100 μM.     

Synthesis of β,β′-edge fused, π-extended porphyrins and their applications in the dye-sensitized solar cells

Four π-extended, β,β′ aromatic ring fused porphyrins including mono- and opp-dibenzoporphyrins bearing two carboxyl groups at only one fused benzo group were synthesized. The optical results by UV–vis spectroscopy indicate that when compared with the absorption spectra of monobenzoporphyrins, greater light-harvesting capabilities can be realized for opp-dibenzoporphyrins with two benzo group at the opposite β,β′ positions of the porphyrin. The photovoltaic properties of these π-extended porphyrins were examined for the first time and the highest conversion efficiency of 1.62% was realized for opp-dibenzoporphyrin 8a-sensitized solar cell, which is ∼60% higher than that of monobenzoporphyrin 4a based solar cell indicating the effect of an extra aromatic π conjugation on the light-harvesting capabilities of π-extended porphyrins. Subsequent DFT calculation results supported our results obtained in the optical and photovoltaic studies.     

Asymmetric synthesis of β′-amino-α,β-enones via addition of α,β-unsaturated ketone-derived enolates to chiral N-phosphonyl imines

Efficient asymmetric Mannich addition reactions between α,β-unsaturated ketone derived enolates and N-phosphonyl imines were reported. These reactions could proceed smoothly for a variety of imine substrates with good (up to 96%) chemical yields and excellent diastereoselectivities (up to 98:2 dr). The method reported in this work provides an easy access to chiral β′-amino-α,β-enones.     

Asymmetric Michael addition of 2-alkoxyphenyl α-substituted nitroacetates to non-prochiral α,β-unsaturated carbonyl compounds catalyzed by podand-type alkali metal 2′-substituted 1,1′-binaphthalen-2-oxides

The asymmetric Michael addition of 2-alkoxyphenyl α-substituted nitroacetates to non-prochiral α,β-unsaturated carbonyl compounds catalyzed by 10 mol % of sodium 2′-[2-(2-methoxyethoxy)ethoxy]-1,1′-binaphthalen-2-oxide gave the desired adducts in high yields with up to 95% ee.     

Total synthesis of bioactive drimane–epoxyquinol hybrid natural products: macrophorin A, 4′-oxomacrophorin A,and 1′-epi-craterellin A

Total synthesis of novel hybrid natural products, merosesquiterpenoids macrophorin A, 4′-oxomacrophorin A, and 1′-epi-craterellin A has been accomplished following a general strategy based on a sacrificial Diels–Alder–retroDiels–Alder approach to control regio- and stereoselectivity.     

Retention studies of 2′-2′-difluorodeoxycytidine and 2′-2′-difluorodeoxyuridine nucleosides and nucleotides on porous graphitic carbon: Development of a liquid chromatography–tandem mass spectrometry method

The development of a method for the separation of 2′-2′-difluorodeoxycytidine (gemcitabine, dFdC), 2′-2′-difluorodeoxyuridine (dFdU) and their mono-, di- and triphosphates using a porous graphitic carbon column (Hypercarb), without ion-pairing agent, is described. The retention of dFdC and dFdU could be controlled with an organic modifier (acetonitrile, CH₃CN) and the retention of the anionic nucleotides with an eluting ion (bicarbonate). Separation of all analytes was achieved using a 0–25 mM ammonium bicarbonate gradient in CH₃CN–H₂O (15:85, v/v). Under these conditions, however, very long re-equilibration times were required. Injection of an acidic solution (100 μL 10% formic acid in H₂O, v/v; 2.65 M) after running a gradient directly restored the separation capabilities of the column. Still, separation between the analytes slowly deteriorated over a period of months. These problems were solved by preconditioning the column with a pH buffered hydrogen peroxide (H₂O₂) solution (0.05% H₂O₂ in CH₃CN–H₂O (15:85, v/v), pH 4) before starting an analytical run. The oxidation of the stationary phase with H₂O₂ prevented its slow reduction, which most likely caused the decreasing retention times. The analytes were detected using tandem mass spectrometry.     

Synthesis and anti-HCV activity of 1-(1′,3′-O-anhydro-3′-C-methyl-β-d-psicofuranosyl)uracil

Synthesis of a novel 1′,2′-oxetane-uridine bearing a 2′-C-methyl substituent, [1-(1′,3′-O-anhydro-3′-C-methyl-β-d-psicofuranosyl)uracil], is described. Key to its construction was the use of 6-O-(p-toluoyl)-1,2:3,4-di-O-isopropylidene-3-C-methyl-d-psicofuranose as a nucleosidation substrate, which itself was derived from d-fructose. Anti-HCV activity was examined for the corresponding triphosphate which was not found to be an inhibitor of HCV NS5B 1b wild type polymerase in vitro. The 1′,2′-oxetane uridine triphosphate without 2′-C-methyl substitution was similarly inactive, however, the guanosine analog displayed modest inhibition (IC₅₀ = 10 μM).     

新型螺[氧化吲哚-3,3′-吡唑]-5′-二氟甲基-4′-甲酸酯类化合物的合成

以原位生成的二氟甲基重氮甲烷（CF₂HCHN₂）与靛红衍生的3-烯基氧化吲哚为原料,通过[3+2]环加成反应和1,3-H迁移过程,合成了3种结构新型的螺[氧化吲哚 3,3′-吡唑]-5′-二氟甲基-4′-甲酸酯类化合物,收率41~68%, dr 91: 9~99 : 1,其结构经¹H NMR, ¹³C NMR, ¹⁹F NMR和HR-MS(ESI-TOF)表征。并通过单晶X-射线单晶衍射确定其相对构型。