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.     

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.     

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。      

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.     

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。     

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.     

Synthesis and transformations of [1,2-O-isopropylidene-α-d-erythro (and α-d-ribo)furanose]-3-spiro-3′-(4′-amino-5′H-2′,3′-dihydroisothiazole-1′,1′-dioxide) derivatives

The carbanion-mediated sulfonamide cyclisations (CSIC protocols) of glyco-α-sulfonamidonitriles derived from readily available uloses 1A and 1B have been investigated using different bases (potassium carbonate, cesium carbonate, LDA and n-BuLi). As a result, a series of enantiomerically pure [1,2-O-isopropylidene-α-d-erythro (and α-d-ribo)furanose]-3-spiro-3′-(4′-amino-5′H-2′,3′-dihydroisothiazole-1′,1′-dioxide) derivatives have been prepared and isolated in good yields.     

新型1-取代-2-(1′,3′-二氧五环-4′-基)苯并咪唑的合成

以地沟油水解副产物甘油和多聚甲醛为原料,经醇醛缩合和次氯酸钠催化氧化反应制得1,3-二氧杂环戊-4-酸(DIC); DIC与邻苯二胺或其衍生物进行酰胺化-环化反应高效地合成了3种新型的1-取代-2-(1′,3′-二氧五环-4′-基)苯并咪唑类化合物,其结构经UV-Vis, ¹H NMR, ¹³C NMR, IR和GC-MS表征。     

β,β′-Linked cofacial bis-porphyrins

The copper(II) porphyrin 1, bearing a fused methylenepropano ring, undergoes an unusual self-sensitized photo-oxygenation reaction in the presence of DBU to give a high yield of a cofacial bis-porphyrin 7 under very mild conditions. The structures of compounds 1 and 7 were confirmed by X-ray crystallography.     

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.     

2,2′-联咪唑合成的改进方法

优化了传统合成及提纯2,2＇-联咪唑的方法,使实验步骤缩减,并使产率和纯度有较大提高。     

临界胶束浓度cmc与饱和吸附Γ′2∞的关系

关于临界胶束浓度cmc(critical micelle concentration)与饱和吸附Г’_(2∞)的关系,一般物理化学教材中描述为:“当表面活性剂(SAA)的浓度足够大时,溶液表面吸附达饱和,表面张力σ不再下降,此时溶液表面层内的表面活性剂分子定向排列而形成单分子膜,若再增     

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.     

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).     

Stereodefined dinucleoside (3′,5′)-propionamidophosphonates and β-cyanoethylphosphonates and their incorporation into modified oligonucleotides

Base-catalyzed stereospecific anti-Markovnikov addition of dinucleoside (3′,5′)-H-phosphonates to the activated alkenes acrylamide and acrylonitrile resulting in the synthesis of P-chiral diastereomerically pure dinucleoside (3′,5′)-alkylphosphonates is reported.     

Gallium(III) selective sensors based on 2-amino-3-(α-N-phenylmethyl-2′-amino-1′,4′-naphthoquinonyl)-1,4 naphthoquinones in poly (vinyl chloride)

Synthesis and application of 2-amino-3-(α-N-phenylmethyl-2′-amino-1′,4′-naphthoquinonyl)-1,4 naphthoquinone (S) as a neutral ionophore for the determination of gallium(III) in PVC-based membrane sensors has been described. The sensor based on membrane composition (w/w, mg%); 5.0 (S):30.0 (PVC):5.0 (KTpClPB):60.0 (o-NPOE) is the best and showed a working range of 2.3 × 10⁻⁷ to 1.0 × 10⁻² M with detection limit of 1.2 × 10⁻⁷ M. It can tolerate non-aqueous media up to 15% with a slope of 19.7 mV decade⁻¹ of activity. The sensor has been used to assess the Ga(III) concentration in different natural samples (peach and tomato leaves, coal-fly-ash and river sediments). It can be used for 2.5 months without any distortion in results, after which, leaching of ionophore was observed from the membrane phase. The proposed sensor has shown a good dynamic response time of 11 s.     

Pronounced effects of grinding on rates of intramolecular electron transfer in mixed-valence 1′,2′,1?,2?-tetranaphthylmethyl- and 1′,3′,1?,3?-tetranaphthylmethyl-biferrocenium triiodides

The X-ray structural determinations of the neutral 1′,2′,1?,2?-tetranaphthylmethylbiferrocene and the mixed-valence 1′,3′,1?,3?-tetranaphthylmethylbiferrocenium triiodide have been determined. Our Mössbauer measurements for mixed-valence 1′,2′,1?,2?-tetranaphthylmethylbiferrocenium triiodide (1) and 1′,3′,1?,3?-tetranaphthylmethylbiferrocenium triiodide (2) indicate that the intramolecular electron-transfer rates in 1 and 2 are quite sensitive to the environmental perturbations caused by the grinding of sample. An interesting finding is that the Mössbauer results indicate that the unground diffusing sample of 1 is valence delocalized on the Mössbauer time scale above 180 K. However, the ground diffusing sample of 1 exhibits a Mössbauer spectrum characteristic of a valence-trapped cation which remains valence-trapped electronic state even at 300 K. The effects of grinding of samples are also observed in the EPR measurements.     

Synthesis and photo-physical properties of methoxy-substituted π-conjugated-2,2′-bipyridines

4,4′-Bis-vinyl-2,2′ bipyridines have been known in the area of materials chemistry since last few decades. Bipyridine molecules bearing donor substituents in their π backbone are examples of ‘push-pull’ molecules. Emissive properties of such ligands depend on the position of the donor unit in their π backbone. The Horner-Wordsworth-Emmons reaction has been used extensively to synthesize such types of conjugated systems. Three newly synthesized highly conjugated 2,2′ bipyridines (3a-c) have been described. The molecules 3a-c are highly emissive in the visible region at room temperature.     

直流磁控溅射磁性γ′-Fe4N膜生长机理研究

采用直流磁控溅射法研究了磁控溅射沉积氮化铁薄膜的生长机制,并归属了其生长普适类型.结果表明,磁控溅射法生长的薄膜表面具有自仿射分形特性,而且表面存在一定数量的空位或孔洞,粒子呈现悬臂沉积生长现象.γ′-Fe4N单相薄膜的生长指数β≈0.61±0.02,静态标度指数α≈0.57±0.20,各指数之间的关系为α+α/β≈2,薄膜生长属于KPZ普适类型.