Synthesis and Antifungal Activity of Novel Chiral α-Aminophosphonates Containing Fluorine Moiety

Chiral α-aminophosphonates were synthesized using （R） or （S）-1-phenylethylamine in the presence of BF3·Et2O under microwave irradiation in moderate to good yields. The new compounds were identified by ^1H NMR, ^19F NMR, IR and elemental analysis. Their antifungal activities were evaluated and some compounds were found to exhibit excellent antifungal activities. To the best of our knowledge, this is the first report on antifungal activity of chiral α-aminophosphonates containing fluorine moiety.     

Synthesis and Biological Activity of New Pyrethroid Acid Oxime－esters Containing Pyrazole Ring

A series of compounds containing oxime-ester linkage and pyrazole ring(in place of the ester linkage and the alcohol moiety in pyrethroid ester) was designed and synthesized. The structures of all the compounds prepared were confirmed by IH NMR and MS spectroscopy as well as elemental analyses. The binassay data of those compounds against tobacco mosaic virus (TMV), cucumber mosaic virus(CMV), potato virus X (PVX) and potato virus Y(PVY) were presented. Among them compound 6i was found to possess significant plant antiviral activities. But all the compounds showed low insecticidal and acaricidal activities.     

Studies on Synthesis and Biological Activities of Novel Triazole Compounds Containing Pyrimidine or N, N－Dialkyldithiocarbamate Ring

Twelve of the title compounds were synthesized. Their structures were identified by means of IR, EA, IH NMR and MS. The IR spectra clearly show that the absorptions in the regions of 1716—1666 cm^-1 and 1505—1499 cm^-1 are the characteristic absorption bands for vc=O and vc=N. In the IH NMR spectra of target compounds(10a—10g), three protons of a = CH—CH2— group present three sets of quartet peaks of the protons. The preliminary bioassays showed that the synthesized compounds exhibited some activities of fungicides and plant growth regulators.     

Synthesis and antioxidant activities of flavonoids derivatives, troxerutin and 3’, 4’, 7-triacetoxyethoxyquercetin

Syntheses of two very important derivatives of quercetin,troxerutin and 3’,4’,7-triacetoxyethoxyquercetin were described.The latter was synthesized by highly selective esterification reaction in first time.The compounds were characterized by NMR,IR and Mass spectroscopy.Additionally,the antioxidant activities of the compounds were tested by means of improved pyrogallol autoxidation method.This was the first in using this method to test the antioxidant activities of these two compounds in vitro.The optimum system of pyorgallol autoxidation spectrophotometry was investigated and established according to the reaction rules.The assay indicated that these compounds showed noticeable antioxidant activities,and compound 2 was much more effective as a free radical scavenger than the compound 1 vitamin C was used as a reference material.     

Novel Reaction of Some Azoles with Dimethyl Sulfoxid

The compounds 4a～4j were prepared by 3a～3j which were prepared from 1a～1j through 2a～2j. The compounds 6a～6j were prepared by the reaction of the products of 4a～4j with dimethyl sulfoxid via Dimroth rearrangement.[1] The compounds ethyl 5-arylamino-1H-1,2,3-triazol-4-carbonates (5a～5d) and ethyl 2-methylthiamethylene-5-arylamino-2H-1,2,3-triazol-4-carbonates (6a～6j) are established by MS, IR, elemental analysis and 1H NMR spectral data. The route of syntheses is shown in Scheme 1.     

5-Alkylpyrrole-2-carboxaldehyde derivatives from the Chinese sponge Mycale lissochela and their PTP1B inhibitory activities

Two new 5-alkylpyrrole-2-carboxaldehyde derivatives,mycalenitrile-15(1) and mycalenitrile-16(2),along with five known related ones(3-7),were isolated from the South China Sea sponge Mycale lissochela.The structures of the new compounds were elucidated on the basis of extensive spectroscopic analysis and by comparison of their NMR data with those reported in the literature.In bioassay,compounds 1 and 7 exhibited significant PTPIB(Protein-tyrosine phosphatase 1B,a recognized target for diabetes and obesity) inhibitory activities with IC_(50) values of 8.6 and 3.1 μmoI/L,respectively.A preliminary SAR analysis of the isolated compounds with their PTP1 B inhibitory effects was described.     

Synthesis and in vitro activities on anti-platelet aggregation of N,N’-di(2-substituted-phenyl)-4-methoxyisophthalamides and benzene- 1,3-disulfonamides

On the propose of searching for the SAR and obtaining novel antiplatelet aggregating drugs,we have described the synthesis procedure and the activities in vitro on antiplatelet aggregation of two series of derivatives,which contain both 18 N.N’-di(2- substitutedphenyl)-4-methoxyisophthalamides(2a-2r) of the 2 series and nine N,N’-di(2-substitutedphenyl)-4-methoxybenzene- 1,3-disulfonamides(3a-3i) of the 3 series.The results showed that three compounds 2e,2i and 3g emerged as significant activities of antiplatelet aggregation,superior to two reference drugs picotamide and aspirin,and eight compounds 2j,2k,21,2o,2p,2q,2r and 3i merely superior to picotamide.The preliminary SAR shows that it is favorable for the 2 series to increase the activities via the steric hindrance substituents attached to the two side chain benzene rings at 2-positions.And the arylamides of the 2 series have better the activity values than the arylsulfonamides of the 3 series respective except for 3b and 3g.On the contrary,electrostatic factors would not contribute evidently to the activities of the two series.The structures of 15 compounds newly synthesized have been established by MS and ~1H NMR and been first reported in this paper.     

Synthesis of dimethyl 3-perfluoroalkyl-4-(3-oxo-2-triphenyl-phosphoranylidenbutanylidene)-pent-2-enedioate and its cyclization

The title compounds 5a-5c were prepared via the reaction of methyl 2-perfluoroal-kynoates (4) with methyl 5-oxo-4-(triphenylphosphoranylidene)hex-2-enoate (3), which was obtained from the reaction of methyl propynate (2) with acetylmethylenetriphenylphosphorane (1) at -5-0℃. Intramolecular elimination of Ph3PO took place when compound 5 was heated in aqueous methanol at 115-120℃ in sealed tube, yielding dimethyl 2-trifluoromethyl-4-methylisophthalate (6a) from 5a and methyl 5-acetyl-4-hydroxy-2-heptafluoropropanylbenzoate (6b) from 5b, respectively. The structures of compounds 5, 6a and 6b were confirmed by IR, MS, 1H NMR, 19F NMR and 13C NMR spectroscopy and elemental analyses. Rection mechanisms for the formation of compounds 5, 6a and 6b were proposed.     

A new bisbenzylisoquinoline alkaloid from Plumulanelumbinis

One new bisbenzylisoquinoline alkaloid, neferine N-oxide(1), along with three known compounds,neferine(2), liensinine(3), and isoliensinine(4), were isolated from Plumulanelumbinis – the embryo of the seed of Nelumbonucifera. Their structures were elucidated by extensive spectroscopic analysis(MS,UV, IR, NMR), and the absolute configurations were determined by experimental circulardichroism(CD)spectra. Compound 1 is a new naturally occurring bisbenzylisoquinoline alkaloid with an N-oxide functionality, and the CD spectrum of(1R, 1'R) neferine is first reported. The antioxidant activities of compounds 1–4 were evaluated using the ORAC assay, which illustrated that all these compounds showed the different levels of oxygen radical absorbance capacity.     

Synthesis,X-ray Crystallographic Analysis and Bioactivities of α-Aminophosphonates Featuring Pyrazole and Fluorine Moieties

A series of novel -aminophosphonates containing pyrazole and fluorine moieties was designed and synthesized through ultrasonic-assisted condensation and solvent-free addition reactions. Their structures were verified by IR, 1H NMR, 13 C NMR and elemental analysis. The crystal structure of diethyl[(4-cyano-1H-pyrazol-3-ylamino)(3,5-difluorophenyl)methyl]phosphonate(4a, C15H17F2N4O3P) was determined by single-crystal X-ray diffraction. Compound 4a crystallizes in the triclinic system, space group P1 with a = 8.381(3), b = 10.103(5), c = 11.268(3) , = 83.772(19), = 74.726(19), = 70.964(18), V = 869.9(6) 3, Mr = 370.30, Dc = 1.414 g/cm3, Z = 2, F(000) = 384, = 0.200 mm-1, Mo Ka radiation( = 0.71073 ), the final R = 0.0487 and w R = 0.0823 for 1582 observed reflections with I 2(I). X-ray diffraction analysis reveals that there are two planes in 4a, and the dihedral angle is 71.51. Two intermolecular hydrogen bonds and a face-to-face ··· stacking interaction are observed in the crystal structure. The compounds were evaluated for their antifungal, antiviral and antitumor activities, respectively. Among them, 4b, 4c, 4g and 4h exhibit good activities on Sclerotium rolfsii Sacc at 200 μg/m L, while 4b, 4c, 4f and 4g possess good anti-TMV activities at 500 μg/m L. Unfortunately, all of the compounds showed weak antitumor activities.     

Synthesis and activities of new 4-hydroxy benzoxazolone derivatives

<正>A series of new 4-substituted benzoxazolone derivatives were synthesized according to a convenient method,their anti-inflammatory and analgesic activities in vivo were evaluated.All of them were new compounds,the structures of all the synthesized compounds were confirmed by ~1H NMR,~(13)C NMR,ESI-MS and HR-MS.Most of the compounds exhibited anti-inflammatory activity.     

Synthesis,Crystal Structure and Antitumor Activities of N,N,1-Triphenyl-1H-benzo[d]imidazol-5-amine Derivatives

In order to discover the novel antitumor agents, a series of N,N,1-triphenyl-~1Hbenzo[d]imidazol-5-amine derivatives were designed and synthesized, and the structures were characterized by IR, H-RMS, ~1H and ~(13)C NMR. X-ray crystallography showed that 4 c is in monoclinic system, space group P1 with a = 9.209(2), b = 9.533(3), c = 14.097(3) ?, β = 102.069(3)°, V = 1202.2(5) ?~3, Z = 2, F(000) = 528, μ = 1.74 mm–1, S = 1.024, the final R = 0.0448 and wR = 0.1109. The in vitro antitumor activities of target compounds were evaluated by MTT assay against human cancer cell lines K562, HL-60, HeLa and BGC-823. The target compounds demonstrated weak or moderate antitumor activities against these cell lines.     

Synthesis and Antiviral Activities of Chiral Thiourea Derivatives

An environmentally benign method has been developed for the synthesis of novel chiral thiourea derivatives in high yields in ionic liquid [Bmim]PF6. The ionic solvent can be recovered and reused without any loss of its activity. The target compounds were characterized by elemental analysis, IR, 1H NMR and 13C NMR spectral data. According to the preliminary bioassay, some of the chiral thiourea analogues exhibited moderate in vivo antiviral activities against TMV at a concentration of 500 mg/L. Title chiral compound 3i was found to possess good in vivo protection, inactivation and curative activities of 57.0%, 96.4% and 55.0%, respectively against TMV with an inhibitory concentration at 500 mg/L. The title chiral compound 3i revealed better inactivation effect on TMV (EC50＝50.8 µg/mL) than Ningnanmycin (EC50＝60.2 µg/mL).     

Design, Synthesis and Synergistic Effects of Novel Derivatives of Solanesol

To further explore the biological activities of solanesylamine derivatives,several novel solanesylpiperazinotriamines and their amides were designed and synthesized,the chemical structures of target compounds were confirmed by IR,1H NMR,MS,and element analysis.The in vitro antitumor activities of the synthetic compounds were assessed by MTT test on L1210 and CHO cells.The preliminary results showed that at low micromolar concentrations these compounds exhibit obvious toxicity against tumor cells,and the synergistic effect on clinical antitumor agent indicated that at noncytotoxic concentrations,they also evidently enhance the curative effect of vincristine(VCR).The synergistic effects of compounds 4a,4c,and 9 were even superior to that of reference compound N,N'-bis(3,4-dimethoxybenzyl)-N-solanesyl-ethylenediamine(SDB).     

Bismuth triflate：A highly efficient catalyst for the synthesis of bio-active coumarin compoundsvia one-pot multi-component reaction

A series of coumarin-chalcone hybrid compounds and coumarins linked to pyrazoline was synthe-sized in good yield and short time using a simple and efficient method. This method involved the one-pot reaction of salicylaldehyde, an α-ketoester and an aromatic aldehyde (in the case of the coumarin-chalcone derivatives) in addition to hydrazine hydrate (in the case of the pyrazolyl cou-marins) in the presence of a catalytic amount of bismuth triflate [Bi(OTf)3, 5 mol%]. The synthesized compounds showed scavenging activity towards the free radical 2,2-diphenyl-1-picrylhydrazyl. All compounds were characterized using IR,1H NMR and13C NMR spectroscopy.     

Design and synthesis of novel triazole derivatives containing γ-lactam as potential antifungal agents

A series of novel triazole derivatives containing γ-lactam were designed and synthesized, and their structures were confirmed by ~1H NMR,~(13)CNMR and HRMS. The in vitro antifungal activities of the target compounds were evaluated. The results showed that all of the compounds exhibited stronger activity against the six clinically important fungi tested than fluconazole. 3D and 3E showed comparative activity against the fungi tested except for Candida glabrata and Aspergillus fumigatus as voriconazole. In addition,the docking model for 2A and CYP51 was investigated.     

Synthesis and anticancer activities of porphyrin induced anticancer drugs

In view of the property of porphyrin's accumulation selectively in tumor,the ftorafur was modified by binding a porphyrin block to improve its tumor targeting and reduce its side effects.These novel porphyrin derivatives and metal compounds were synthesized under mild conditions with satisfactory yield,and the constructions of all these new compounds were characterized by UV,IR,MS, ~1H NMR spectra and elementary analysis.Their anticancer activities were evaluated by MTT assay;the results indicated that the anticancer activities of compounds 4a-c were twice as high as that of ftorafur.     

Design, synthesis and antiproliferative activities of novel 5H-pyridazino[4,5-b]indoles

A novel series of 5H-pyridazino[4,5-b]indoles were designed and synthesized in order to find novel potent anticancer compounds.The structures were confirmed by ~1H NMR and MS.Their antiproliferative activities against two cancer cell lines were tested by the MTT method in vitro.Three of compounds (1e,1g,and 1h) exhibited potent antiproliferative activities,especially compound 1h (with IC_(50) values of 5.2μmol/L and 1.9μmol/L against Bel-7402 and HT-1080,respectively).The preliminary structure-activity relationships of 5H-pyridazino[4,5-b]indole derivatives were discussed.     

Solvent-and Catalyst-free Synthesis and Antifungal Activities of α-Aminophosphonate Containing Cyclopropane Moiety

Nine new α-aminophosphonate derivatives containing cyclopropane moiety have been synthesized via conventional and microwave irradiation methods under solvent-and catalyst-free condition. The structures of the title compounds have been confirmed by 1H NMR, 31P NMR, FTIR, EI-MS and FTICR-MS. Their antifungal activities were evaluated in vivo and some of the compounds were found to exhibit excellent antifungal activities against Corynespora cassiicola, Pseudomonas syringae pv. Lachrymans, Pseudoperonospora cubensis and Sclerotinia sclerotiorum.     

Design and synthesis of novel triazole antifungal derivatives based on the active site of fungal lanosterol 14a-demethylase （CYP51）

A series of 1-(1H-1,2,4-triazole-1-y1)-2-(2,4-difluorophenyl)-3-(N-isoproyl-N-substituted-amino)-2-propanols have been designed and synthesized on the basis of the active site of lanosterol 14a-demethylase(CYP51).Their structures were confirmed by MS and ~1H NMR.In vitro antifungal activities of these synthesized compounds were evaluated against eight human pathogenic fungi.The results showed that all title compounds exhibited activity against fungi tested to some extent.Compounds 3c,3d,7a,7b and 7c exhi...