1-苯基-3-(3'-吲哚基)-5-取代苯基-2-吡唑啉的合成及1H NMR和MS中的取代基效应

J-(3'-吲哚基)-3-取代苯基-2-丙烯-1-酮与茉肼反应,合成了10种新的1-苯基-3-(3'-吲哚基)-5-取代苯基-2-吡唑啉衍生物,其结构通过各种波谱证实.讨论了此系列化合物¹HNMR和Ms中的取代基效应,得出取代基常数σ或σ⁺与质子化学位移,碎片相对丰度之间存在着良好的线性关系.     

几种取代螺吲哚啉萘并噁嗪的合成

螺吲哚啉-2,3'-[3H]萘并[2,1-b][1,4]噁嗪(简称螺噁嗪)是一类耐光疲劳性能优于螺吡喃的光致变色物^[1]。Fox以及Ono先期合成了这类化合物^[2],最近Pottier等考察了取代基对性能的影响^[3,4]。但所涉及的取代基(CH₃、CH₃O、Cl、NO₂)多在母体结构中吲哚环的5( 6)位,且N-烷基碳链较短,蔡环上有取代基的情形较少见^[5]。     

3-烷氧基-3-烷基异吲哚啉-1-酮的合成

为探索3-亚烷基异吲哚啉-1-酮在有机合成中的应用潜力，构建新型的异吲哚啉-1-酮类化合物，本文以3-亚烷基异吲哚啉-1-酮和醇为原料，在三氯硅烷与路易斯碱催化剂作用下发生加成反应，得到一系列3-烷氧基-3-烷基异吲哚啉-1-酮类化合物，并初步尝试了以手性路易斯碱催化该反应。综上，本文建立了一种新型异吲哚啉-1-酮类化合物的合成方法，该方法条件具有温和、操作便捷、底物适用范围广和收率普遍较高的特点。     

双官能团硫脲催化吲哚-3-酮对β,γ-不饱和酮酯的不对称Michael加成反应研究（英文）

通过双官能团硫脲催化的吲哚-3-酮对不饱和酮酯的不对称Michael加成反应研究,以很高的产率、很好的对映选择性和非常好的非对映选择性得到了手性的2-取代吲哚-3-酮类化合物,对吲哚类化合物的手性合成具有积极意义.     

吲哚-2-甲酸和(S)-吲哚啉-2-甲酸的合成和相互转化研究进展

吲哚-2-甲酸和(S)-吲哚啉-2-甲酸均是具有生物活性的天然产物和众多降压药的特征结构片段,报道了它们的合成及其相互转化研究进展.吲哚啉-2-甲酸可由吲哚-2-甲酸还原制得,其中(S)-吲哚啉-2-甲酸可由外消旋体拆分或通过不对称合成法制备,其中"手性源法"作为一种新出现的方法具有较好的前景.吲哚-2-甲酸可由Fischer吲哚合成法制备,或通过取代苯胺或苯甲醛制备,也可通过吲哚啉衍生物氧化脱氢制备,其中Fischer合成法仍具有较强的竞争力.     

不对称傅-克反应在构建手性3-取代吲哚中的研究进展

由于手性3-取代吲哚化合物是许多具有生物活性天然产物和药物分子的核心骨架,其合成方法的研究就格外令人注目.尤其是近二十年来,利用手性金属配合物和有机小分子催化剂实现吲哚的C(3)位不对称傅-克烷基化反应已成为有机界广泛研究的热点.按照促进不对称傅-克烷基化反应的手性催化剂进行分类,就近年来其在3-取代吲哚化合物合成中的应用加以综述,并对今后的发展方向进行了展望.     

新型多取代3-烯基吲哚的合成

开发了一种以吲哚为起始原料,合成具有多个反应位点的多取代3-烯基吲哚的新方法,合成了9个目标化合物,其中8个为新化合物,其结构经¹H NMR, ¹³C NMR和HR-MS(ESI)表征。     

3-芳氧基-1-丙胺类HIV-1 Tat/PCAF BRD抑制剂的合成及生物活性

为了研究HIV-1 Tat/PCAF BRD抑制剂的构效关系, 合成了6个3-芳氧基-1-丙胺类化合物. 以取代的2-硝基苯酚为起始原料, 在常规加热和微波辐射加热下与1,3-二溴丙烷反应合成3-(2-硝基芳氧基)-1-溴丙烷(3), 结果显示, 微波辐射加热比常规加热下的反应速度明显加快, 收率有所提高. 3和邻苯二甲酰亚胺钾进行N-烷基化反应合成了2-[3-(芳氧基)-丙基]二氢异吲哚-1,3-二酮, 再经肼解得到了目标化合物, 所有化合物的结构均经FTIR, ¹H NMR, ¹³C NMR及HRMS确证. ELISA检测法测定了它们体外抑制HIV-1 Tat/PCAF BRD的活性, 并对影响活性的因素进行了讨论.     

E,E-1-(3＇-吲哚基)-5-取代苯基-1,4-戊二烯-3-酮化合物的合成及抗炎活性

戊二烯酮化合物;E;E-1-(3＇-吲哚基)-5-取代苯基-1;4-戊二烯-3-酮化合物的合成及抗炎活性     

新型二氢色原酮拼接多环吡咯螺环氧化吲哚类化合物的 无催化剂合成及其抗白血病活性

以取代的3-羧酸活化色酮、靛红与消旋脯氨酸为原料，乙腈为溶剂，依次经1,3-偶极子[3+2]环加成和脱羧反应，合成了8个新型的二氢色原酮拼接多环吡咯螺环氧化吲哚类化合物 (3a~3h)，产率68%~87%, dr值15/1~20/1,其结构经¹H NMR, ¹³C NMR和HR-MS（ESI-TOF）表征。采用MTT法研究了3a~3h对人白血病细胞(K562)的体外抑制活性。结果表明：化合物3d,3f, 3g对K562具有一定的抑制活性(IC₅₀=46.3~69.4 μmol·L^-1)。     

Enantioseparation of selected chiral sulfoxides using polysaccharide-type chiral stationary phases and polar organic, polar aqueous-organic and normal-phase eluents

HPLC enantioseparation of selected chiral sulfoxides was studied using cellulose and amylose phenylcarbamate derivatives as chiral stationary phases (CSPs). The contributions of various functional groups of a chiral analyte as well as the polysaccharide derivatives in the analyte retention and chiral recognition were evaluated. A very high enantioseparation factor exceeding 110 was observed in the enantioseparation of 2-(benzylsulfinyl)benzamide (BSBA) on cellulose tris(3,5-dichlorophenylcarbamate) (CDCPC) CSP by using 2-propanol as a mobile phase. The enantiomer elution order was opposite on cellulose and amylose phenylcarbamates. For the polysaccharide-type CSPs, pure alcohols such as methanol, ethanol and 2-propanol represent a valuable alternative to more common alcohol-hydrocarbon and reversed-phase eluents.     

Chromatographic Enantioseparation of Ten Amino Acid Amide Derivatives on Three Polysaccharide-Based Chiral Stationary Phases

Enantioseparation of ten kinds of amino acid amide derivatives bearing aniline moieties on three polysaccharide-based chiral stationary phases (CSPs) was first systematically investigated. The chromatographic experiments were performed in the normal phase mode, namely, with n-hexane and 2-propanol as mobile phase. The effects of chiral columns, concentration of 2-propanol and column temperature on the enantioseparation were studied in detail. These compounds can be well resolved on Chiralcel OD-H column with the resolution above 1.5. Enantioseparation mechanism of chiral analytes and the CSPs are proposed based on the thermodynamic analysis of the experimental data. Our study establishes a simple, fast and efficient analytical method for amino acid amide derivatives by chiral HPLC, and provides a reference for enantioseparation of chiral amino acid amide derivatives and similar chiral compounds.     

Generation and reactivity of enantiomeric (BINOLato)Ni+ complexes with chiral secondary alcohols in the gas phase

In the presence of secondary alcohols, electrospray ionization of dilute methanolic solutions of nickel(II) salts and 1,1'-bis-2-naphthol (BINOL) leads to complexes of the formal composition [(BINOLato)Ni(CH3CH(OH)R)]+ (BINOLato refers to a singly deprotonated (R)- or (S)-1,1'-bis-2-naphthol ligand; R=CH3, C2H5, n-C3H7, n-C4H9, n-C5H11, n-C6H13, c-C6H11, and C6H5). Upon collision-induced dissociation, each mass-selected nickel complex either loses the entire secondary alcohol ligand or undergoes bond activation followed by elimination of the corresponding ketone, as revealed by deuterium labeling. When enantiomeric BINOLato ligands (R or S) are combined with chiral secondary alcohols (R or S), differences in the branching ratios between these channels for the two stereoisomers of the secondary alcohols provide insight into the chiral discrimination operative in the C--H- and O--H-bond activation processes. For saturated alkan-2-ols, the chiral discrimination is low, and if any preference is observed at all, ketone elimination from the homochiral complexes (R,R and S,S) is slightly favored. In contrast, the diastereomeric (BINOLato)Ni+ complexes of 1-phenylethanol exhibit preferential ketone losses for the heterochiral systems (S,R and R,S).     

The influence of mobile phase demixion on thin-layer chromatographic enantioseparation of ibuprofen and naproxen

In our earlier article we presented the results of tracing the enantioseparation of the two test analytes (ibuprofen and naproxen) by means of video densitometry and scanning densitometry. In that way we demonstrated an excellent performance of this combined approach to the thin-layer chromatographic detection in the area of enantioseparation. In this paper we study an impact of the four different mobile phases on the enantioseparation of the scalemic mixtures of ibuprofen and naproxen on the silica gel layers impregnated with L-arginine as chiral selector. The main component of all the investigated mobile phases is 2-propanol. Mobile phase 1 consists of pure 2-propanol, while mobile phases 2-4 contain, respectively, ca. 0.66, 1.32, and 1.98 g/L of glacial acetic acid in 2-propanol. Acetic acid is used to protonate L-arginine, as the involved retention mechanism consists of the ion pair formation between L-arginine in the cationic form and the chiral 2-arylpropionic acids (2-APAs), ibuprofen and naproxen, in the anionic form. It is shown that in the absence of glacial acetic acid no enantioseparation can be obtained. Then with adding of 0.66 g/L glacial acetic acid partial enantioseparation of the naproxen and ibuprofen antimers is obtained, with a simultaneous effect of the mobile phase demixion. With the amount of acetic acid increasing, the effect of demixion becomes increasingly perceptible. In that case the displacement effect is observed (and mathematically modeled), which results in compressing of the antimer pairs by the second front of mobile phase. The obtained results allow a deeper insight into the mechanism of enantioseparation with the two test 2-APAs. A combined impact of the crystalline chirality of silica gel and the molecular chirality of L-arginine on the vertical and the horizontal enantioseparation of ibuprofen and naproxen is also discussed.     

Enantiomeric resolution of five chiral pesticides on a Chiralpak IB-H column by SFC

The enantiomeric separations of five chiral pesticides, diclofopmethyl, 1; benalaxy, 2; acetofenate, 3; myclobutanil, 4; and difenoconazole, 5, were conducted on a Chiralpak IB-H column by a packed-column supercritical fluid chromatography (p-SFC). All compounds, except difenoconazole and myclobutanil, were well resolved within 10 min. As the mobile phase polarity decreased through changing the percentage and the type of alcohol modifiers in the supercritical carbon dioxide (CO(2)), the retention time, the separation factors, and the resolution increased. However, based on the retention time and the resolution, the optimized separations were obtained with the mobile phase containing 10% 2-propanol for diclofop-methyl 1; benalaxy, 2; myclobutanil, 4; difenoconazole, 5; and containing 3% 2-propanol for acetofenate, 3. The optimized separation temperature was at 35°C under the supercritical fluid condition. The π-π interactions and the hydrogen bonding interactions between Chiralpak IB-H CSP and the analytes might be the main chiral discriminations on enantioseparation of these five pesticides.     

Enantioseparation of 2-aryloxypropionic acids on chiral porous monolithic columns by capillary electrochromatography. Evaluation of column performance and enantioselectivity

The enantioseparation of 2-aryloxypropionic acids by capillary electrochromatography was tested on columns with a monolithic stationary phase prepared from silanized fused-silica capillaries (100 microm I.D.) by in situ copolymerization of glycidyl methacrylate, ethylene glycol dimethacrylate and methyl methacrylate in the presence of formamide and 1-propanol as the porogen solvents. The porous chiral monolithic stationary phases were prepared by reaction of the epoxy-groups at the surface of the monolith with (+)-1-(4-aminobutyl)-(5R,8S,10R)-terguride. To attain the minimum HETP values for the enantiodiscrimination of 2-phenoxypropionic acid, the influence of the composition of polymerization solution on column total porosity and efficiency was investigated. Optimum mobile phase conditions were found for all analytes tested using acetonitrile-methanol mixtures containing triethylamine and acetic acid as the buffer components. Furthermore, the chemical and mechanical stabilities of the columns were satisfactory, allowing hundreds of analyses.     

High-performance liquid chromatographic enantioseparation of beta-amino acid stereoisomers on a (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid-based chiral stationary phase

Direct reversed-phase high-performance liquid chromatographic methods were developed for the separation of enantiomers of 14 unnatural beta-amino acids, including several beta-3-homo-amino acids on a chiral stationary phase containing (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid bonded to 3-aminopropyl silica gel as chiral selector. The effects of the organic and the acidic modifiers and the mobile phase composition on the separation were investigated. The natures and positions of the substituents on the aromatic ring substantially influenced the retention and enantioseparation. The elution sequence in most cases was determined and the R enantiomers were eluteted before the S enantiomers.     

Characterization of Column Hold-Up Volume with Static and Dynamic Methods on an Immobilized Polysaccharide-Based Chiral Stationary Phase

Polysaccharide-based chiral stationary phases (CSPs) are efficient for enantioseparation of many chiral compounds. Immobilized polysaccharide CSP, as used in the Chiralpak IA column, is a new configuration that was recently introduced for application in chiral separation. As shown in several previous studies, the characteristics of Chiralpak IA columns cannot be simply extrapolated from the coated version. In this study, hold-up volume of a Chiralpak IA column was evaluated by static and dynamic methods. The static pyconometry method gave similar hold-up volumes either as an average value from a range of solvents or a direct measurement from the carbon tetrachloride-isopropanol (IPA) solvent pair. The dynamic method with 1,3,5-tri-tert-butylbenzene (TTBB) was influenced by the ratio of n-hexane and 2-propanol in the mobile phase but not by the dissolving solvent of TTBB. The two methods resulted in the same hold-up volume of ∼3.0 mL. TTBB showed weaker retention on the IA column after correction of isobaric thermal expansion of the mobile phase. During temperature variations in the range of 15–50 °C, the hold-up volume of TTBB was highly reproducible. Results of this study improve our understanding of the chromatographic features of the immobilized polysaccharide IA column.     

Enantiomeric resolution of new triazole compounds by high-performance liquid chromatography

Cellulose tris(3,5-dimethylphenylcarbamate) (CDMPC) was synthesized and coated on aminopropylsilica to prepare a chiral stationary phase (CSP). HPLC methods were developed for the direct enantioseparation of 12 chiral triazole compounds on the CSP. The separations were made using normal phase methodology with a mobile phase consisting of n-hexane-alcohol (ethanol, 1-propanol, 1-butanol, 2-propanol, and t-butanol) in various portions. The column temperatures were studied for the optimization of the resolutions. The effects of structural features of the solutes on the discrimination between the enantiomers were examined. Baseline separation was easily obtained in many cases.     

Chromatographic resolution and isotherm determination of (R,S)-mandelic acid on Chiralcel-OD column

Resolution of racemic mandelic acid ((R,S)-MA) and numerical determination of binary competitive isotherm of (R,S)-MA on Chiralcel-OD column have been investigated in this study. The effects of the alcohol modifier and acidic additive in the mobile phase on the retention and enantioseparation of (R,S)-MA were studied at first. The inverse method was then used to determine the competitive isotherm parameters of (R,S)-MA by minimizing the sum of square deviations of the model predictions from the measured elution profiles. The results indicate that the mobile phase with 85% hexane/15% isopropanol/0.3% trifluoroacetic acid mixture gives the best resolution of (R,S)-MA and competitive-modified Langmuir isotherm provides the more accurate sorption mechanism of (R,S)-MA on the cellulose tris(3,5-dimethylphenylcarbamate) chiral stationary phase.