A CONVENIENT SYNTHESIS OF LONG-CHAIN 3-n-ALKYLTHIOPHENES AND 3-n- ALKYLFURANS

Abstract

The syntheses of 3-substituted long-chain furans and thiophenes by a Wittig reaction are described. ¹H-NMR and UV data of these compounds are reported.     

Precise discovery of a STAT3 inhibitor from Eupatorium lindleyanum and evaluation of its activity of anti-triple-negative breast cancer

Michael reaction acceptors (MRAs) are a class of active compounds. There is a great prospect to screen STAT3 inhibitors from Eupatorium lindleyanum, furthermore, to discover lead compounds for anti-triple-negative breast cancer (TNBC). In this study, glutathione (GSH) was employed, and a UPLC-MS screening method was developed to discover MRAs. We screened MRAs which can inhibit STAT3 using a STAT3-dependent reporter system. Six sesquiterpene lactones, including a new compound Eupalinolide O (1), together with five known compounds, Eupalinolide I (2), Eupalinolide K (3), Eupalinolide H (4), Eupalinolide J (5) and Eupalinolide G (6) were isolated. Eupalinolide J was identified as MRA that decreased luciferase activity of STAT3. Preliminary activity assessment showed that Eupalinolide J could inhibit the viability of TNBC cell lines. We demonstrated that Eupalinolide J, which is a natural typical MRA, has a notable inhibition of STAT3 activity and a potential cytotoxic activity against TNBC cell lines.     

[3 + 3] Cycloaddition of aza-oxyallyl cations with 1,4-dithiane-2,5-diols for the construction of 3-thiomorpholinones

Abstract

Base-mediated [3?+?3] cycloaddition reaction of in-situ formed aza-oxyallyl cations and 1,4-dithiane-2,5-diols has been achieved under mild reaction conditions. This strategy provides direct and efficient access to prepare desired thiomorpholin-3-one derivatives in moderate-to-high yields. The approach features broad substrates scope and short reaction time. Moreover, the resulting products can be readily converted into other useful heterocyclic compounds including 2H-1,4-thiazin-3(4H)-ones and thiomorpholine-3,5-diones.     

Synthesis and Biological Activity of 2-Hydroxy-N(5-methylene-4-oxo-2-aryl-thiazolidin-3-yl)-benzamide

2-Hydroxy benzoic acid hydrazide (1) undergoes facile condensation with aromatic aldehydes to afford the corresponding 2-hydroxy benzoic acid arylidene hydrazides (2a–h) in good yields. Cyclocondensation of compounds 2a–h with thioglycolic acid yields 2-hydroxy-N(4-oxo-2-aryl-thiazolidin-3-yl)-benzamides (3a–h). These 3a–h compounds are for the reacted with benzaldehyde in the presence of sodium ethanolate affords, giving 2-hydroxy-N(5-methylene-4-oxo-2-aryl-thiazolidin-3-yl)-benzamides (4a–h). The structures of these compounds were established on the basis of analytical and spectral data. All the newly synthesized compounds were evaluated for their antibacterial and antifungal activities.

Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.     

Lipolytic effect of compounds isolated from leaves of mulberry (Morus alba L.) in 3T3-L1 adipocytes

In this study, 19 known compounds were isolated from mulberry (Morus alba L.) leaves. The lipid accumulation inhibitory activity of the isolated compounds was investigated. Compounds 4 and 12 showed good anti-adipogenic activity based on 3T3-L1 adipocytes with values of 36.6 ± 9.0 and 34.7 ± 4.0%, respectively. In addition, compounds 3, 6 and 15 showed significant inhibitory activity with values from 15.4 to 21.2% and compounds 2, 8–9 and 17–18 exhibited weak activity with values ranging from 2.1 to 10.7% at a concentration of 40.0 μM. These results show the potentiality that mulberry leaf is an excellent inhibitory phytochemical source against lipid accumulation.     

Phosphazenyl Derivatives,R3P˭NX

Abstract

The synthesis, reactions, physical properties, and structures of phosphazenyl derivatives, R₃P?NX are discussed. Of the three types of bond formation involved in the synthesis of phosphazenyl compounds (a) R—P, (b) P?N, and (c) N—X, the greatest accent is placed on (b) and (c). R can be Cl, Ph, Me, NMe₂, OAlk etc.; X can be Ar, SO₂-p-tol, N₃C₃Cl₂, N₃P₃C₁₅, N₄P₄F₇, etc. Basicities, bond lengths and angles, conformations, and spectroscopic properties are analysed.     

Synthesis of a Tetra- and a Hexasaccharide Donor Corresponding to the Non-Reducing Termini of Mycobacterial 3-O-Methylmannose Polysaccharide (MMP)

Abstract

The blockwise synthesis of the title compounds, namely the tetra- and the hexasaccharide trichloroacetimidates (20) and (23), is described. Both acetates and imidates were employed as glycosyl donors in most of the coupling reactions. As nearly all of the synthetic intermediates contain one or more OCH₃ groups, they are easily identified by NMR spectroscopy the methyl signals. The fully functionalized compounds 20 and 23 correspond to the non-reducing terminal fragments of mycobacterial 3-O-methylmannose polysaccharide (MMP), and can serve as suitable building blocks for the synthesis of higher-order structures of MMP.     

Ab Initio Study of the Dehydrogenation of 3-Pyrroline, 2,5-Dihydrofuran and 2,5-Dihydrothiophene

Abstract

The nature of the transition state structures of the decomposition of 3-pyrroline (1), 2,5-dihydrofuran (2) and 2,5-dihydrothiophene (3) were investigated usingab initio Molecular Orbital (MO) and Density Factional Theory (DFT) methods. The energy barrierof the decomposition of compound 1 is smaller than compound 2 and compound 2 is smaller than compound 3. The energy barriers for the decomposition of compounds 1–3 are 46.20, 50.17, and 61.34 kcal mol^?1, respectively, which is calculated by B3LYP/6-31G^*//HF/6-31G^* level of theory. Which is ingood agreement with reported experimental data. Contrary to the previously reported data, the distance between the cis-2-and-5-hydrogen atoms in compound 1 is greater than compound 2. The transition-state structures of the decomposition of compounds 1–3 are formed by interaction of the cis-2-and-5-hydrogen atoms. Also, the rings of compounds 1–3 in the transition state structures are puckered.     

3-O-乙酰基熊果酸3-乙酰基-2-[(未)取代苯基]-2,3-二氢-1,3, -噁二唑-5-甲酯的合成及其抗炎活性研究

熊果酸与氯乙酸乙酯反应制得熊果酸乙氧甲酰基甲酯(2), 2与水合肼反应得到熊果酸甲酰肼甲酯(3), 3与羰基化合物反应得到一系列酰腙4a～4g, 再将4a～4g与乙酸酐作用, 环合得到3-O-乙酰基熊果酸3-乙酰基-2-[(未)取代苯基]-2,3-二氢-1,3,4-噁二唑-5-甲酯(5a～5g). 15个新化合物均未见文献报道, 其结构经¹H NMR, IR, MS加以确证, 并进行了药理结果筛选. 结果表明, 部分化合物具有良好的抗炎活性. 其中, 化合物5a (40 mg•kg^－1), 5d (40 mg•kg^－1), 5g (40 mg•kg^－1)与熊果酸相比, 具有更强的疗效.     

神经节苷脂GM3的有效合成

报道了α-Neu5Ac-(2-3)-β-Gal-(1-4)-β-Glc-(1-1)-Cer (GM3)的有效合成方法. 将选择性保护的乳糖二醇与唾液酸黄原酸酯(Xanthate)在AgOTf/PhSCl催化下高立体、高区域选择性糖苷化得到含唾液酸的三糖, 经脱苄基保护及全乙酰化后, 在温和条件下脱去还原端保护基, 并制备成三氯乙酰亚胺酯糖苷, 与选择性保护的鞘氨醇缩合得到含叠氮化合物9. 后者用Ph₃P还原后, 在EDC存在下与硬脂酸酰化反应, 得化合物11, 脱去保护基后获得目标产物GM3 (1), 为研究肿瘤疫苗提供有用材料. 化合物结构经NMR, MS和HRMS确证.     

3-(3-叔丁氧基)丁二酰亚胺基单环β-内酰胺衍生物的合成

从苹果酸出发, 经过一系列反应得到3-(3-叔丁氧基)丁二酰亚胺乙酰氯. 3-(3-叔丁氧基)丁二酰亚胺乙酰氯和含不同取代基的Schiff碱1a～1h反应得到8个新的3-(3-叔丁氧基)丁二酰亚胺基单环β-内酰胺衍生物2a～2h, 化合物2a～2h的结构经IR, ¹H NMR, MS和元素分析所确证.     

NEW AND CONVENIENT SYNTHESIS OF (R) AND (S) OF 2-METHYL-3-OXA-5-(TERT-BUTYLDIPHENYLSILYLOXYL) METHYLPENTANOATE AND 2-METHYL-3-OXA-5- (TERT-BUTYLDIMETHYLSILYLOXYL)METHYLPENTANOATE

Abstract

(R) and (S) of 2-Methy1-3-oxa-5-(tert-butyldiphenylsilyloxyl)methy1pentanoate (4a. 6a) and (R) and (S) of 2-methy1-3-oxa-5-(tert-butyldimethylsilyloxyl)methylpentanoate (4b, 6b) were synthesized by the reaction of the preparative compounds (2a, 2b) with (R) and (S) methy1lactate (3, 4) in the presence of a silver (1) oxide catalyst (Method B). The title compounds are useful for the synthesis of different natural products such as epothilones.     

A 3D-QSAR CoMSIA study on 3-azolylmethylindoles as anti-leishmanial agents

A three-dimensional quantitative structure-activity relationship (3D-QSAR) study using Comparative Molecular Similarity Indices Analysis (CoMSIA) was conducted on a series of 3-azolylmethylindoles as anti-leishmanial agents. Evaluation of 24 compounds synthesized in our laboratory served to establish the model. A random search was performed on the library of compounds, and molecules of the training set were aligned on common elements of template molecule 13, one of the most active compounds. The best predictions were obtained from multifit procedure with a CoMSIA model combining steric, electrostatic, hydrophobic and hydrogen bond acceptor fields (q ²?=?0.594, r ²?=?0.897). The model was validated using an external test set of 7 compounds giving a satisfactory predictive r ² value of 0.649. Information obtained from CoMSIA contour maps could be used for further design of more promising inhibitors.     

A Micropreparative HPLC Purification Procedure for (G-3H)-Benzo(a)-Pyrene and 3-(6-14C)-Methylcholanthrene

Abstract

This paper describes a micropreparative purification method of (³G)-benzo(a)pyrene and 3-(6-¹⁴C)-methylcholanthrene employing high pressure reversed phase chromatography. The method can be used immediately prior to the use of these compounds as exposure agents in metabolism studies, thereby assuring the highest possible degree of purity during exposure and thereby eliminating the need for batch purification and repetitive sampling from the purified material.     

The First Examples of 1-Aza-3-phosphabenzenes

Abstract

The hitherto unknown 1-aza-3-phosphabenzenes are obtained via regiospecific Diels-Alder reaction with inverse electron demand of 2-trifluormethyl-4-methyl-6H-1,3-oxazin-6-on with phosphaalkynes. The primary cycloaddition adducts extrude carbon dioxide under the reaction conditions (80°C, no solvent, 3 days in a sealed tube) and cannot be isolated. The resulting 1-aza-3-phosphabenzenes are relatively stable compounds and are completely spectroscopically characterized.     

New isothiocyanatotolane liquid crystals with terminal but-3-enyl substitute

Four kinds of new but-3-enyl-based isothiocyanate liquid crystals composed of tolane core and but-3-enyl terminal group (A1–A4) were synthesised via seven step reactions based on 2-(4-bromophenethyl)-1,3-dioxolane, and four n-butyl analogues B1–B4 as comparison structures were also prepared. The mesomorphic properties and physical properties of the compounds were investigated. Single fluorinated compounds A2 and A3 exhibit monotropic nematic phase, and they have lower melting enthalpy and higher clearing points than those of the comparison compounds B2 and B3. The non-fluoro-substituted compound A1 and difluorinated compound A4 exhibit no nematic phase. Replacement of n-butyl chain by but-3-enyl as terminal group is enabled to increase birefringence (Δn ~ 0.394–0.430) and reduce rotational viscosity. These isothiocyanatotolanes with terminal but-3-enyl substitution have potential application for high birefringence mixtures.     

Interaction in Systems Ln2O3-CsPO3 and Ln2O3- UO3-CPO3

Abstract

The systems Ln₂O₃-CsPO₃ and Ln₂O₃-UO₃-CsPO₃ were investigated and three sets of compounds A, B, C were isolated.     

3-(4-吡啶基)-4-(6-取代色酮-3-基-亚甲氨基)-5-芳氨基-1,2,4-三唑的合成

N-芳基-N'-[(4-吡啶基)羰基]氨基硫脲用85%的水合肼环化, 得到3-(4-吡啶基)-4-氨基-5-芳氨基-1,2,4-三唑(2a～2c). 然后再与3-甲酰基色酮(3a～3d)反应, 制备得到了一系列新化合物: 3-(4-吡啶基)-4-(6-取代色酮-3-基亚甲氨基)-5-芳氨基-1,2,4-三唑(4a～4c, 5a～5c, 6a～6c, 7a～7c). 化合物的结构经元素分析, IR, ¹H NMR和MS确证.     

Synthesis and antiproliferative evaluation of bis-styrylbenzothiazol-3-ium salts

A series of bis-styrylbenzothiazol-3-ium salts containing different substituents 4–12 were synthesized from 2-methylbenzothiazole by condensation of quaternary salts 1–3 with p-substituted benzaldehydes. All compounds were characterized by IR, ¹H and ¹³C NMR, MS, and elemental analysis. Synthesized compounds 4–12 were screened for antitumor activities. Based on presented in vitro screening results we may conclude that compounds 4–6 and 9 showed the best cell growth inhibitory activity.     

Green chemistry approach to the synthesis of 3-substituted-quinazolin-4(3H)-ones and 2-methyl-3-substituted-quinazolin-4(3H)-ones and biological evaluation

ABSTRACT

A synthesis of two series of 3-substituted quinazolinones was performed utilizing a green chemistry approach, deep eutectic solvents and microwaves, namely. 2-Methyl-3-substituted-quinazolin-4(3H)-one derivatives were synthesized in a two-step reaction, using choline chloride:urea deep eutectic solvent (DES). 3-Substituted-quinazolin-4(3H)-ones were synthesized in one-pot one-step reaction of anthranilic acid, amines and orthoester in a microwave reactor. For the synthesis of 2-methyl-3-substituted-quinazolin-4(3H)-ones, first conventional synthesis of benzoxazinone, as an intermediate, was performed. Further, benzoxazinone in reaction with corresponding amines, in choline choline:urea deep eutectic solvent, furnished desired compounds. These procedures are based on green principles with the aim of developing synthetic routes for the potential antitumor agents. All compounds were characterized by LC/MS, ¹H NMR and ¹³C NMR spectral techniques. Compound 1 bearing trifluoromethoxyphenyl group showed promising activity against HuT-78 cell line with IC₅₀ of 51.4?±?5.1?µM.