New chroman derivatives from the Japanese liverworts Metacalypogeia cordifolia and Cephalozia otaruensis.

The diethyl ether extract of the Japanese liverwort Metacalypogeia cordifolia yielded five new chroman type derivatives in addition to known sesquiterpenoids. One of the new chroman derivatives was also isolated from the ether extract of another liverwort, Cephalozia otaruensis. Their structures were established by extensive two dimensional (2D) NMR techniques and chemical evidence. They were shown to be 2,2-dimethyl-7-(3-methyl-2-butenyl)-chroman derivatives. This was the first example of the isolation of the chroman-type compounds, although various types of aromatic compounds have been isolated from liverworts.     

Synthesis of biologically potent new 3-(heteroaryl)aminocoumarin derivatives via Buchwald-Hartwig C-N coupling

New 3-(heteroaryl)aminocoumarin derivatives were synthesized from 3-aminocoumarin, applying optimized Buchwald-Hartwig amination conditions using Palladium acetate, Cesium carbonate, and BINAP in 1,4-dioxane employing elevated temperature conditions and under an argon atmosphere. The target heteroarylaminocoumarin derivatives were obtained in moderate to good yields ranging from 56% to 98%. The procedure described could be widely employed for the preparation of new heterocyclic compounds when one of the core moieties is coumarin and has the potential to be active drug candidates.     

Novel Substituted Imidazo[2,1‐b][1,3,4]Thiadiazole Derivatives: Synthesis,Characterization, Molecular Docking Study,and Investigation of Their In Vitro Antifungal Activities

In this study, a new series of substituted imidazo[2,1‐b][1,3,4]thiadiazole derivatives were synthesized. To this end, first 2‐amino‐1,3,4‐thiadiazole derivatives (compounds 2a and 2b ), the starting materials, were synthesized with high yields (82% and 79%, respectively). Then imidazo[2,1‐b][1,3,4]thiadiazole derivatives ( 4 – 16 ), the target compounds, were synthesized from reactions of 2‐amino‐1,3,4‐thiadiazole derivatives ( 2a and 2b ) with 2‐bromoacetophenone derivatives ( 3a – 3i ) (in yields of 52% to 71%). All of the synthesized compounds were characterized by ¹H NMR, ¹³C NMR, Fourier transform infrared, elemental analysis, mass spectroscopy, and X‐ray diffraction analysis (compounds 4 – 12 , 14 , and 15 ) techniques. In vitro antifungal activity tests were performed for all of the synthesized compounds. Inhibition zones, percentage of inhibition, minimum fungicidal activity, minimum inhibitory concentration, and lethal dose values of the target compounds were determined against some plant pathogens. According to the results of the biological activity tests, all of the synthesized compounds showed moderate to high levels of antifungal activity. Theoretical calculations were performed to support the experimental results. The geometric parameters of selected compounds ( 5 , 6 , and 8 ) were optimized using the density functional theory B3LYP/6‐31G(d) method in the Gaussian 09W package program, and the frontier molecular orbitals (highest occupied molecular orbital–lowest unoccupied molecular orbital) were calculated theoretically. Finally, molecular docking studies were performed for antifungal activity studies of the selected compounds and to determine whether or not these compounds could be inhibitor agents for the 2RKV protein structure.     

New imide 5-HT1A receptor ligands - modification of terminal fragment geometry

Two sets of new o-methoxyphenylpiperazine (MPP; series a) and 1,2,3,4-tetrahydroisoquinoline (THIQ; series b) derivatives, containing various imide moieties derived from NAN190, were synthesized and evaluated in vitro for their ability to bind to the serotonin 5-HT(1A) and 5-HT(2A) receptors. All new derivatives from series a demonstrated high 5-HT(1A) affinities, whereas THIQ analogues were much less active. With respect to 5-HT(2A) receptors, three MPP derivatives presented moderate activity but the rest of the investigated compounds were practically inactive. The influence of changes in terminus geometry on 5-HT(1A) receptor affinity was analyzed in regard to model compounds NAN190and MM199.     

Design and synthesis of new N-(5-trifluoromethyl)-1H-1,2,4-triazol-3-yl benzenesulfonamides as possible antimalarial prototypes

A rational approach was used to synthesize a new set of 15 1H-1,2,4-triazol-3-yl benzenesulfonamide derivatives with the aim of developing new antimalarial lead compounds. These derivatives were prepared in yields between 50% and 62%, and their structures were elucidated using IR, 1H-, 13C-, 1?F-NMR, MS and elemental analysis. A docking study based on sulfonamides previously used against malaria identified trifluoromethyl-substituted derivatives to be the best lead compounds for new antimalarial drug development.     

新型2－乙内酰硫脲衍生物的合成与表征

新型2－乙内酰硫脲衍生物的合成与表征;乙酰乳酸合成酶;磺酰脲;乙内酰硫脲;合成     

1-苯基-3-甲基-6-N,N-二正丁基胺-2(1H)-喹喔啉-2-酮的全合成

报道了2(1H)-喹喔啉类衍生物——1-苯基-3-甲基-6-N,N-二正丁基胺-2(1H)-喹喔啉-2-酮的全合成.该化合物及其中间体1-苯基-3-甲基-6-胺基-2(1H)-喹喔啉-2-酮和1-苯基-3-甲基-6-硝基-2(1H)-喹喔啉-2-酮均为新化合物,文中给出了它们的重要的分析数据,简要讨论了溶剂在关环反应以及N-烷基化反应中的重要影响,偶然发现以水作溶剂时关环主产物为1-苯基-3-甲基-5-硝基-苯并咪唑.这类化合物可应用于药物,如用作N-甲基-D-天冬氨酸(NMDA)受体及α-氨基羟甲基异噁唑丙酸(AMMPA)受体拮抗剂、杀菌剂等;还可用作植物生长抑制剂、荧光探针以及作为新型功能染料中间体等诸多领域.     

含(4,4′-二氟苯)甲酮肟醚官能团的1,2,3-三氮唑衍生物的合成及抗菌活性研究

以(4,4′-二氟苯)甲酮、盐酸羟胺、苄溴及溴丙炔为原料,应用5 mol%的CuI为催化剂,DMF-H 2O(1∶1)为溶剂,在70℃反应4h以23~81%的收率制得了9个含有(4,4′-二氟苯)甲酮肟醚官能团的1,2,3-三氮唑衍生物5(a~i)。合成的9个目标化合物通过熔点测定和质谱、红外光谱、核磁共振氢谱分析对其结构进行确证。经体外抗菌活性测试表明有4个化合物对时对所测试的大肠杆菌具有明显的抑制活性,其MIC为32ug·mL^-1。     

Two new quinones from Iris bungei

Two new benzoquinone derivatives, bungeiquinone (1) and dihydrobungeiquinone (2), and two known derivatives, 3-hydroxyirisquinone (3) and 3-hydroxydihydroirisquinone (4), were isolated from the roots of Iris bungei. The structures of the new compounds were established on the basis of spectroscopic methods.     

硝基苯并咪唑衍生物的合成、表征及抑菌活性的测定

以苯并咪唑为原料,经硝化、二茂铁磺酰化等步骤,合成了8种未见文献报道的硝基苯并咪唑衍生物,其结构经MS,¹H NMR和元素分析确证.由于硝基苯并咪唑的互变异构,二茂铁磺酰化后,产生两个异构体,用X射线衍射仪测定了化合物2a的晶体结构.初步的抑菌实验结果表明,该系列化合物具有良好的抑菌作用,其抑菌活性均优于对照药剂50%多菌灵可湿性粉剂.     

Two new isoaurones derivatives from Callistephus chinensis flower

Two new isoaurones derivatives were obtained from Callistephus chinensis flower. Their structures were elucidated on the basis of extensive spectroscopic analyses. Both of the new compounds were evaluated cytotoxic activity. Phytochemical investigation of Callistephus chinensis flower led to the isolation of two new isoaurones derivatives (Z)-4′,4,10-trihydroxy-siamaurone (1) and (E)-4′,4,10-trihydroxy-siamaurone (2). The structures of these new compounds were identified by the interpretation of spectroscopic data (mainly 1D and 2D NMR) and by comparison with data reported in the literature. Both of the new compounds were evaluated for their cytotoxicity.     

Conformational control of flexible molecules: design and synthesis of novel chiral 1,5-diaza-cis-decalins

Control of the conformational equilibria of 1,5-diaza-cis-decalins, a new class of chiral diamine ligands, has been investigated. Chiral 2,6- and 3,7-substituted derivatives of 1,5-diaza-cis-decalins were designed to stabilize the conformational form needed to chelate a lithium. These derivatives were synthesized in optically pure form starting from 1,5-diaza-cis-decalin. Due to the rigid and conformationally well-defined nature of these compounds, the potential of these compounds as chiral diamine ligands was investigated. Asymmetric lithiation-substitution reactions of N-Boc-pyrrolidine and N,N-diisopropyl-o-ethylbenzamide were performed using these ligands and up to 60% ee was obtained. For the latter substrate, results spanning a range from 32% ee (R) to 60% ee (S) were obtained (Delta ee = 92%) with 1,5-diaza-cis-decalin ligands differing only in the location of two methyl substituents. Unlike many other diamines that have been employed in asymmetric lithiation-substitution reactions, the limited conformational flexibility of the 1,5-diaza-cis-decalins is analogous to (-)-sparteine such that these results may permit the construction of structure-activity relationships.     

Comparison of methods for extraction,storage, and silylation of pentafluorobenzyl derivatives of carbonyl compounds and multi-functional carbonyl compounds

The employment of O-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine (PFBHA) derivatization along with bis-(trimethylsilyl)trifluoroacetamide (BSTFA) or N, N-( tert-butyldimethylsilyl)trifluoroacetamide (MTBSTFA) derivatization is a popular method for measurement of oxygenated organics in environmental and biological samples. Most notably, the derivatization method enables the measurement of atmospheric photooxidation products not detected by using other methods. PFBHA derivatization is often conducted in an aqueous solution. Accordingly, experiments were performed to compare the efficiency of hexane, methyl- tert-butyl ether (MTBE), and dichloromethane (CH(2)Cl(2)) for extraction of O-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine (PFBHA) derivatives of carbonyl compounds from water. Further, the stability of these compounds when stored at 4 degrees C in CH(2)Cl(2) was determined, and commonly used methods for silylation of -OH and -COOH groups on the PFBHA derivatives were compared. Overall, CH(2)Cl(2)was the most efficient solvent for extraction of PFBHA derivatives of hydroxycarbonyl compounds, dicarbonyl compounds, and keto-acids from water. Derivatives of carbonyl compounds that do not have secondary functional groups were extracted with approximately equal efficiency by each of the three solvents examined. The PFBHA derivatives of aromatic and saturated aliphatic carbonyl compounds and hydroxycarbonyl compounds were stable in CH(2)Cl(2) at 4 degrees C for > or = 66 days whereas the derivatives of keto-acids and unsaturated aliphatic aldehydes begin to degrade after approximately 38 days. Comparison of four procedures for bis-(trimethylsilyl)trifluoroacetamide (BSTFA) derivatization of -OH and -COOH groups on PFBHA derivatives revealed that primary -OH groups react efficiently in 20-100% BSTFA in CH(2)Cl(2), and do not require a catalyst. Secondary -OH groups also react efficiently in 20-100% BSTFA, but the reaction yield improves slightly when trimethylchlorosilane (TMCS) is added as a catalyst. Reaction of tertiary -OH groups with BSTFA was very inefficient, but improved with addition of 10% TMCS to the BSTFA solution. Finally, -COOH groups seemed to react most efficiently and consistently in 100% BSTFA, without catalyst.     

Integrating approach to discover novel bergenin derivatives and phenolics with antioxidant and anti-inflammatory activities from bio-active fraction of Syzygium brachythyrsum

Syzygium brachythyrsum is an important folk medicinal and edible plant in Yunnan ethnic minority community of China, however, little is known about the chemical and bio-active properties. The present study is aimed to identify the bioactive constituents with antioxidant and anti-inflammatory properties by an integrating approach. First, two new bergenin derivatives, brachythol A (1) and brachythol B (2), together with eleven known phenolic compounds (3–13) were isolated from bioactive fractions by phytochemical method. Among these isolated chemicals, five bergenin derivatives, along with 3 phenolics were found in Syzygium genus for the first time. Then, a further chemical investigation based on ultra-high-performance liquid chromatography-Q Exactive Orbitrap mass spectrometry resulted in a total of 107 compounds characterized in the bio-active fractions, including 50 bergenin derivatives, among which 14 bergenin derivatives and 14 phenolics were potential new natural chemicals. Most of the isolated compounds showed obvious antioxidant activities, while compounds 11, 12, and 13 had favorable performance. Eight compounds (2–5, 7, and 9–11) showed good inhibitory activity on nitric oxide (NO) production in macrophage RAW 264.7 cells. The structure–activity correlation analysis indicated that the antioxidation and anti-inflammatory activities enhanced when bergenin was esterified with gallic acid, caffeic acid or ferulic acid. This is the first report of bergenins in Syzygium genus and the richness in new bio-active bergenins and gallic acid derivatives indicated that Syzygium brachythyrsum is a promising functional and medicinal resource.     

Complete assignments of 1H and 13C NMR data for trypanocidal eremantholide C oxide derivatives

The chemical transformations of eremantholide C (1), a trypanocidal sesquiterpene lactone isolated from Lychnophora trichocarpha Spreng., gave five new oxide derivatives: 3'-hydroxyeremantholide C (2), 1'-formyleremantholide C (3), 1'-carboxyeremantholide C (4), 1'-carbomethoxyeremantholide C (5) and sodium 1'-carboxylate of eremantholide C (6). The (1)H and (13)C NMR data of all these derivatives were assigned based on 1D and 2D techniques. The derivatives were evaluated against Y and CL strains of Trypanosoma cruzi. All of them were inactive against the Y strain. Compounds 2 and 5 displayed 100% activity on the CL strain while compounds 4 and 6 were partially active on the CL strain.     

Anticancer effect of A-ring or/and C-ring modified oleanolic acid derivatives on KB, MCF-7 and HeLa cell lines

New A-ring or/and C-ring modified methyl oleanolate derivatives were prepared. New simple method of synthesis of 3,12-diketone (3) from methyl oleanonate (2) was worked out. The obtained new compounds were tested for cytotoxic activity on KB, MCF-7 and HeLa cell lines. The derivatives had acetoxy, oxo or hydroxyimino function at the C-3 position and in some cases oxo, hydroxyimino or acyloxyimino group at the C-12 position. Almost all of the compounds showed strong cytotoxic activity, higher than unchanged oleanolic acid. The most active substances turned out to be the derivatives with acyloxyimino function, especially 4 and 8d.     

Synthesis and Antimicrobial Evaluation of Novel Derivatives of Semicarbazide and 1,2,4‐triazole

Reaction of phenoxyacetic acid hydrazide with isocyanate was used to the synthesis of new semicarbazide derivatives. Cyclization of these compounds in a 2% aqueous solution of sodium hydroxide led to formation of 1,2,4‐triazole‐3‐one. The chemical structure of synthesized compounds was confirmed by elemental analysis and spectroscopic methods (¹H and ¹³C NMR). On the basis of the NMR, spectra were found that cyclic compounds 1,2,4‐triazole exist in the ‐one form. Moreover, all derivatives were examined for their in vitro activity against some species of bacteria. New compounds presented mild or moderate antimicrobial activity only against reference Gram‐positive bacteria. Two derivatives (one semicarbazide and one triazole) showed bactericidal or bacteriostatic activity.     

取代嘧啶衍生物抗前列腺癌活性的3D-QSAR研究

运用比较分子力场分析(CoMFA)方法,建立18种取代嘧啶衍生物抗前列腺癌活性(pM)的三维定量构效关系。训练集中15个化合物用于建立预测模型,测试集13个化合物(含10号模板分子和新设计的9个分子)作为模型验证。建立的CoMFA模型的交叉验证系数(R_ev²)、非交叉验证系数(R²)分别为0.344、0.935,说明所建模型具有较强的鲁棒性和良好的预测能力。该模型中立体场、静电场贡献率依次为71.6%、28.6%。影响取代嘧啶衍生物抗前列腺癌活性的主要因素是取代基的疏水作用和空间位阻,其次是取代基的库仑力、氢键及配位作用。基于此研究结果,设计了9个新化合物,其抗前列腺癌活性有待医学实验验证。     

Synthesis of new condensed and cyclized coumarin derivatives

Condensation of 4-chloro-2-oxo-2H-chromene-3-carbonitrile with selected heteroarylamines in acetonitrile containing a catalytic amount of triethylamine, followed by intramolecular cyclization, gave the new coumarin derivatives with yields ranging from 43 % to 78 %. The novel compounds were subjected to acid hydrolysis giving the corresponding oxo derivatives in 66–70 % yield. The structural assignments of the synthesized compounds were based on elemental, IR, ¹H and ¹³C NMR analyses.