Synthesis and Investigation of 1,2,3,4-Thiatriazol-5-ylcarbamates

Methyl 1,2,3,4-thiatriazol-5-ylcarbamate (2a), ethyl 1,2,3,4-thiatriazol-5-ylcarbamate (2b), 2-butyl 1,2,3,4-thiatriazol-5-ylcarbamate (2c), allyl 1,2,3,4-thiatriazol-5-ylcarbamate (2d), and 3-(1,2,3,4-thiatriazol-5-yl)oxazolidin-2-one (2e) were synthesized with high yields by the reaction of the corresponding carbon(isothiocyanatidic) acid, alkyl esters, and sodium azide in aqueous solution. The compounds were characterized by ¹H, ¹³C, and ¹⁵N NMR, vibrational spectroscopy (IR), and single crystal X-ray diffraction. The thermal stability was investigated by differential scanning calorimetry.     

Synthesis and Antimicrobial Properties of New Thiosemicarbazide, 1,2,4-Triazole,and 1,3,4-Thiadiazole Derivatives of Sulfanylacetic Acid

Abstract

1,2,4-triazole and 1,3,4-thiadiazole derivatives are still considered a viable lead structure for the synthesis of more efficient antimicrobial agents having a broad spectrum of activity. This study presents the synthesis and antimicrobial evaluation of a new series of substituted 1,2,4-triazole and 1,3,4-thiadiazole derivatives. Reaction of 4-phenyl-5-(pyridin-3-yl)-4H-1,2,4-triazole-3-thione with ethyl bromoacetate yields the corresponding ethyl acetate (1). In the subsequent reaction with 100% hydrazine hydrate, the hydrazide (2) was obtained, which was converted with isothiocyanates to new acyl derivatives of thiosemicarbazide (3a–l). The cyclization of these compounds in alkaline media resulted in the formation of new derivatives of 1,2,4-triazole (4a–i), whereas in acidic media new derivatives of 1,3,4-thiadiazole (5a,b,g) were obtained. All synthesized compounds were screened for their in vitro antimicrobial activities.     

Synthesis,characterization and biological evaluation of some novel sulfonylthiosemicarbazides

Abstract

A series of thiosemicarbazides were synthesized and structurally characterized by spectroscopic techniques (NMR, FT-IR) besides elemental analysis. These compounds were evaluated for their cytotoxicity against human breast cancer cell line MCF7 and prostate cancer cell line PC3 and nonmalignant fibroblast L929 cell line by MTT assay. Among the compounds, N-[2-(4-chlorophenyl)ethyl]-2-[(4-methylphenyl)sulfonyl]hydrazinecarbothioamide (3d) and 2-[(4-methylphenyl)sulfonyl]-N-[4-(trifluoromethoxy)phenyl]hydrazinecarbothioamide (3f) were found to display significant cytotoxicity with IC₅₀ of 13.87?μM (against PC3 cell line) and 1.47?μM (against MCF7 cell line), respectively. These compounds were non-cytotoxic to normal cell line with IC₅₀>100?μM. Western blotting studies demonstrated that compound 3f induced apoptosis and caused cell death in the MCF7 and PC3 cell lines via an increase in Bax protein expression and a slight decrease in Bcl-2 protein expression. The gene expression ratio Bax/Bcl-2 showed the induction of mitochondrial apoptosis in cancer cell lines. All of synthesized compounds have also been tested for antioxidant activity and all compounds achieved strong inhibition of the DPPH radical. These findings showed that compound 3f, displays potential to be further explored in the development of new anticancer agents.     

1-[18F]Fluoroethyleneglycol-2-nitroimidazoles, a new class of potential hypoxia PET markers

Summary 1-[2-(2-Fluoroethoxy)ethyl]-2-1H-nitroimidazole (3a), 1-{2-[2-(2-fluoroethoxy)ethoxy]ethyl}-2-1H-nitroimidazole (3b) and 1-(2-{2-[2-(2-fluoroethoxy)ethoxy]ethoxy}ethyl)-2-1H-nitroimidazole (3c) were synthesized in a two step sequence.Coupling the ditosylate of di-, tri- or tetraethylene glycol with 2-nitroimidazole followed by fluoride substitution afforded the reference compounds in high yield and¹⁸F labeling gave the corresponding markers in 70-82% radiochemical yield.     

Synthetic Studies on Sialoglycoconjugates 7: Synthesis of N-Acetylneuraminic Acid Derivatives and Analogs

ABSTRACT

Various types of the O-protected derivatives and the 9-bromo analogs of methyl [2-(trimethylsilyl)ethyl 5-acetamido-3, 5-dideoxy-D-glycero-α-D-galacto-2-nonulopyranosid]onate were synthesized from methyl [2-(trimetnyl-silyl)ethyl 5-acetamido-4, 7-di-O-acetyl-3, 5-dideoxy-D-glycero-α-D-galacto-2-nonulopyranosid]onate (1) or methyl [2-(trimethylsilyl)ethyl 5-acetamido-8, 9-di-O-isopropylidene-D-glycero-α-D-galacto-2-nonulopyranosidlonate (3).     

Synthesis and Inhibitory Activity Against Epstein-Barr Virus of Some New 1,2,3,4-Tetrahydropyrimidine-2-thiones

1,2,3,4-Tetrahydropyrimidine-2-thiones 4a–n were synthesized through the reaction of aromatic aldehydes 1a–n , ethyl acetoacetate (2) and thiourea ( 3) . The structures of all newly synthesized heterocyclic compounds elucidated by the use of IR, ¹H NMR, mass spectra, and elemental analyses. The inhibitory activity against the Epstein-Barr Virus early antigen (EBA-VA) of all newly synthesized heterocyclic compounds were evaluated.     

Synthesis and properties of 5-ferrocenyl-1H-pyrazole-3-carbaldehydes

New ferrocene derivatives - ethyl esters of 1-aryl-5-ferrocenyl-1H-pyrazole-3-carboxylic acids were synthesized. The corresponding aldehydes were obtained from acid esters in two steps. The reductive amination reaction of 5-ferrocenyl-1-phenyl-1H-pyrazole-3-carbaldehyde was studied. Several of these compounds were investigated by cyclic voltammetry. All of them exhibited a reversible one-electron oxidation-reduction wave owing to the ferrocene-ferricinium redox couple with a positive shift (0.51-0.69 V) compared with that of ferrocene (0.46 V). The X-ray crystal structure of the ethyl ether 1-(3-chloro-2-fluorophenyl)-5-ferrocenyl-1H-pyrazole-3-carboxylic acid is also presented.     

N-(5-氯-2-羟苯基)氨基酸酯的合成、表征及抑菌活性

以5-Cl水杨醛和L-苯丙氨酸、L-亮氨酸及L-甘氨酸的脂肪酸酯为原料,通过碱催化的席夫碱缩合反应,合成了6种N-（5-氯-2-羟苄基）席夫碱氨基酸酯及其还原产物N-（5-氯-2-羟苄基）氨基酸酯。 化合物的结构及组成经过IR、¹H NMR和元素分析测试技术进行了表征。 合成的席夫碱及其还原产物对革兰氏阴性菌、革兰氏阳性菌及真菌均有不同程度的抑制作用。 质量分数为0.01%的N-（5-氯-2-羟苄基）席夫碱氨基酸酯对大肠杆菌的抑菌率达90%以上,而N-（5-氯-2-羟苄基）氨基酸酯对金黄色葡萄球菌的抑菌率也在90%以上,均为强抑菌活性,其中N-（5-氯-2-羟苄基）苯丙氨酸酯的抑菌率达98%以上。     

Studies on a three-step preparation of β-fluoroalkyl acrylates from fluoroacetic esters

β-Fluoroalkyl-acrylic esters are valuable building blocks for the synthesis of organofluorine compounds. Although the preparation of several β-fluoroalkyl-acrylates is known, a general and straightforward lab-scale methodology for the preparation of multigram amounts of these compounds from fluoroacetic esters is not available, and the related chemistry has not been investigated in detail. We now describe an optimized three-step protocol relying on: (1) Claisen-type condensation of fluoroacetic esters with ethyl acetate, using LDA as base; (2) reduction of the resulting γ-fluoro-β-keto esters by NaBH₄, using toluene or benzene as solvents; (3) P₂O₅-promoted dehydration of the intermediate γ-fluoro-β-hydroxy esters. The methodology affords preparatively useful yields of the target compounds incorporating only fluorine atoms (CF₃, CHF₂, C₂F₅), whereas the γ-halodifluoromethyl (CClF₂, CBrF₂, CIF₂) acrylates could not be obtained in analytically pure form from the dehydration step.     

Synthesis and antitumor activity evaluation of some 1, 2, 4-triazine and fused triazine derivatives

Reactions of 3-hyrazino-5,6-diphenyl-1,2,4-triazine with various carbonyl compounds such as ethyl acetoacetate, acetylacetone, benzoin, isatin, phthalic anhydride, phenyl isocyanate and acetic anhydride were discussed. Its reactions with α, β unsaturated compounds such as arylidinemalononitrile, diethyl acetylenedicarboxylate, dibenzylidine hydrazine were studied. These reactions led to the formation of various triazine and fused-triazine derivatives. The antitumor activity of the synthesized compounds was tested against HePG2 and MCF-7 cell lines. Some of the tested compounds were most active, whereas other compounds exhibited little or no activity.     

Synthesis,reactions, and antioxidant activity of 3-(pyrrol-1-yl)-4,6-dimethyl selenolo[2,3-b]pyridine derivatives

Ethyl 4,6-dimethyl-3-(pyrrol-1-yl) selenolo[2,3-b]pyridine-2-carboxylate (2) was synthesized by the reaction of previously prepared ethyl 3-amino-4,6-dimethyl selenolo[2,3-b]pyridine-2-carboxylate (1) with 2,5-dimethoxytetrahydrofuran in acetic acid. The pyrrolyl ester (2) was converted into the corresponding carbohydrazide 3 which reacted with acetyl acetone, aromatic aldehydes, carbon disulfide in pyridine, and sodium nitrite to afford the corresponding dimethyl pyrazolyl 4, arylidene carbohydrazides 5a–d, oxadiazolyl thiole 6, and caboazide compound 8, respectively. The carboazide 8 reacted with different alcohols and amines to give the corresponding carbamates 9a–c and the aryl urea derivatives 10a–d. Heating of carboazide 8 in dry xylene afforded the pyridoselenolo-pyrrolopyrazinone 11. The latter compound was used as a versatile starting precursor for synthesis of other pyridoselenolo-pyrrolopyrazine compounds. The newly synthesized compounds and their derivatives were characterized by elemental analysis and spectroscopy (IR, ¹H-NMR, and mass spectra). Some of the newly synthesized pyrrolyl selenolopyridine compounds showed remarkable antioxidant activity compared to ascorbic acid.     

Synthesis,Characterization, and Spectroscopic Properties of Hexa(4-Bromo-2-Formyl-Phenoxy)Cyclotriphosphazene and Hexa(4-Chloro-2-Formyl-Phenoxy)Cyclotriphosphazene and Fully Substituted Cyclotriphosphazene Derivatives Bearing a Schiff Base at Room Temperature

Abstract

Hexa(4-bromo-2-formyl-phenoxy)cyclotriphosphazene (2) and hexa(4-chloro-2- formyl-phenoxy)cyclotriphosphazene (3) were obtained from the reactions of hexachloro- cyclotriphosphazene (1) with 5-bromosalicylaldehyde and 5-chlorosalicylaldehyde in the presence of (C₂H₅)₃N and K₂CO₃ at room temperature, respectively. The new two organocyclotriphosphazenes bearing formyl groups were reacted with 4-cyano aniline, 2-phenyl aniline, 4-aceto aniline, 5-chloro-2-hydroxy aniline, 2-hydroxy aniline, 4-hydroxy aniline, 2-(4-morpholino)ethyl amine, 4-carboxy aniline, 4-carbomoyl aniline, 2-mercapto aniline, and 5-amino isoquonoline to prepare cyclotriphosphazene derivatives containing a Schiff base at room temperature. However, fully phenoxy-substituted cyclotriphosphazenes containing a Schiff base were isolated from the reactions of the compound 2 and 3 with 5-chloro-2-hydroxy aniline, 2-hydroxy aniline, 4-hydroxy aniline, and 2-(4-morpholino)ethyl amine. The structures of the synthesized compounds were characterized by elemental analysis, IR, and NMR (¹H, ¹³C, ³¹P) spectroscopy. According to the results of the analysis, all synthesized compounds were found to be fully substituted organocyclotriphosphazenes, such as hexa[4-bromo-2-(5-chloro-2-hydroxy-pheyliminomethyl)phenoxy]cyclotriphosphaze (2a). All cyclotriphosphazene derivatives synthesized gave fluorescence emission peaks in range between 300 nm and 410 nm.     

Synthetic Studies on Sialoglycoconjugates 7: Synthesis of N-Acetylneuraminic Acid Derivatives and Analogs

Abstract

Various types of the O-protected derivatives and the 9-bromo analogs of methyl [2-(trimethylsilyl)ethyl 5-acetamido-3,5-dideoxy-D-glycero-α-D-galacto-2-nonulopyranosid]onate were synthesized from methyl [2-(trimethyl-silyl)ethyl 5-acetamido-4,7-di-O-acetyl-3,5-dideoxy-D-glycero-α-D-galacto-2-nonulopyranosid]onate (1) or methyl [2-(trimethylsilyl)ethyl 5-acetamido-8,9-di-O-isopropylidene-D-glycero-α-D-galacto-2-nonulopyranosid]onate (3).     

Synthesis,antioxidant and antitumor activities of some of new cyclobutane containing triazoles derivatives

Abstract

Thiosemicarbazides (2a–e) were obtained by the interaction of furan-2-carboxylic acid hydrazide (1) with five different isothiocyanate (RNCS) derivatives. By addition of KOH to the reaction medium, ethyl, allyl, phenyl and benzyl, p-tolyl substituted 1,2,4-triazoles (3a–e) were obtained. 3a–e were dissolved in dry acetone containing K₂CO₃ in the presence of 2-chloro-1-(3-methyl-3-mesitylcyclobutyl) ethanone (4) to give 3,4,5-trisubstituted 1,2,4-triazole sulfanyl compounds containing a cyclobutane ring (5a–e). The structures of the final compounds were confirmed by elemental analyses, FT-IR, ¹H-NMR and ¹³C-NMR. The antioxidant and antitumor properties of the synthesized compounds were also investigated. Three of the triazole derivatives with p-tolyl, benzyl and phenyl substituents (5c–e) displayed good antioxidant and antitumor activity in comparison to the standards.     

Efficient synthesis of 2,6-disubstituted-5-hydroxy-3-oxo-2,3-dihydro-pyridazine-4-carboxylic acid ethyl esters

A general procedure is described for the preparation of 6-substituted-5-hydroxy-3-oxo-2,3-dihydro-pyridazine-4-carboxylic acid ethyl esters (6-substituted-5-hydroxy-3(2H)-pyridazinone-4-carboxylic acid ethyl esters). These compounds are shown to undergo selective alkylation at the 2-position in moderate to good yields (19-77%) to afford 2,6-disubstituted-5-hydroxy-3-oxo-2,3-dihydro-pyridazine-4-carboxylic acid ethyl esters (2,6-disubstituted-5-hydroxy-3(2H)-pyridazinone-4-carboxylic acid ethyl esters).     

A convenient synthesis of ethyl 3,3,3,-trifluoropropanoate and its 2-bromo derivative

Ethyl 3,3,3-trifluoropropanoate and ethyl 2-bromo-3,3,3-trifluoropropanoate have been synthesized. A common intermediate ethyl 3-chloro (or 3-bromo)-3,3-difluoropropanoate is involved in the two syntheses. These esters are obtained by oxidation of the corresponding acetals resulting from the radical addition of CF₂BrCl or CF₂Br₂ to ethyl vinyl ether.     

Reaction of 2-cyano[(4-oxo-4H-chromen-3-yl)methylidene]acetohydrazide with phosphorus reagents: Synthesis and evaluation of anticancer activities of some novel 1,2-azaphospholes, 1,2,3-diazaphospholidine,and 1,3,2-diaza-phosphinanes bearing a chromone ring

A series of 1,2-azaphospholes, 1,2,3-diazaphospholidine, 1,3,2-diaza-phosphinanes bearing a chromone ring as well as dialkyl pyrazolopyrimidine phosphonates have been synthesized from treatment of multifunctional 2-cyano[(4-oxo-4H-chromen-3-yl)methylidene]acetohydrazide (2), some phosphorus reagents such as phosphonic acid and its esters, and phosphorus sulfides as well as phosphorus halides in dry dioxane. The isolated products were evaluated for their anticancer activities and on the expression of vascular endothelial growth factor (VEGF) inhibition. Among the isolated products, compounds 3 and 10 exhibited higher effect against breast cancer cells than the reference drug and on the expression of VEGF inhibition.     

One-Pot,Multicomponent Condensation Reaction in Neutral Conditions: Synthesis,Characterization, and Biological Studies of Fused Thiazolo[2,3-b]quinazolinone Derivatives

A new series of 12-(2-chloro-6-quinoline-3-yl)-3,3,8-substituted-2,3,4,12-tetrahydro-benzo[4,5]thiazolo[2,3-b]quinazolin-1-ones 4 was synthesized in one pot by condensing various 2-chloro-3-formylquinolines 1, 2-amino-6-substituted-benzothiazoles 2, and 1,3-cyclohexanedione 3 in ethanol. All the compounds were characterized by IR, ¹H NMR, ¹³C NMR spectra and elemental analysis. All the synthesized compounds were screened for their antibacterial activity against Grampositive bacterial species Bacillus cereus and Bacillus substilus, Gram-negative bacterial species Escherichia coli, and their fungicidal activity against Aspergillus niger, Fuserium oxisporum, and Rhizopus species.     

SYNTHESIS OF SOME NEW 3-ARYLOXYMETHYL- 4-PHENYL-5-(N-SUBSTITUTED CARBOXAMIDOMETHYLTHI0)-S-TRIAZOLES

Abstract

3-Aryloxymethyl-4-phenyl-5-mercapto-s-triazoles (I_a-c) have been synthesized and reacted with N-chloroacetyl derivatives of aromatic and/or heterocyclic amines to yield 5-(N-aryl/heterocyclyl)-carboxamidomethyl thio-s-triazole derivatives 2_a-o and 3_a-o respectively. Reaction of I_a-u with ethyl chloroacetate gave the corresponding esters 4_a-c which were reacted with hydrazine hydrate to give hydrazides 5_a-c. Condensation of 5_a-c with aromatic aldehydes gave Schiff s bases 6_a-u with on cycloaddition reaction with thioglycolic acid yielded 4-thiazolidinones 7_a-g. Some of these compounds were screened in vitro for their antibacterial activities.     

Synthetic Studies on Sialoglycoconjugates 90: Total Synthesis of Sulfated Glucuronyl Paraglobosides

ABSTRACT

3-O-Sulfo glucuronyl paragloboside derivatives (pentasaccharides) have been synthesized. The important intermediate designed for a facile sulfation in the last step and effective, stereocontrolled glycosidation, methyl (4-O-acetyl-2-O-benzoyl-3-O-levulinoyl-α-D-glucopyranosyl trichloroacetimidate)uronate (8) was prepared from methyl [2-(trimethylsilyl)ethyl β-D-glucopyranosid]uronate (3) via selective 4-O-acetylation, 2-O-benzoylation, 3-O-levulinoylation, removal of the 2-(trimethylsilyl)ethyl group and imidate formation. The glycosylation of 8 with 2-(trimethylsilyl)ethyl 2,4,6-tri-O-benzyl-β-D-galactopyranoside (9) using trimethylsilyl trifluoromethanesulfonate gave 2-(trimethylsilyl)ethyl O-(methyl 4-O-acetyl-2-O-benzoyl-3-O-levulinoyl-β-D-glucopyranosyluronate)-(1→3)-2,4,6-tri-O-benzyl-β-D-galactopyranoside (10), which was transformed via removal of the benzyl group, benzoylation, removal of the 2-(trimethylsilyl)ethyl group and imidate formation into the disaccharide donor 13. On the other hand, 2-(trimethylsilyl)ethyl O-(2-acetamido-3,6-di-O-benzyl-2-deoxy-β-D-glucopyranosyl)-(1→3)-O-(2,4,6-tri-O-benzyl-β-D-galactopyranosyl)-(1→4)-2,3,6-tri-O-benzyl-β-D-glucopyranoside (20) as the acceptor was prepared from 2-(trimethylsilyl)ethyl 3,6-di-O-benzyl-2-deoxy-2-phthalimido-β-D-glucopyranoside (14) via O-acetylation, removal of the 2-(trimethylsilyl)ethyl group, imidate formation, coupling with 2-(trimethylsilyl)ethyl O-(2,4,6-tri-O-benzyl-β-D-galactopyranosyl)-(1→4)-2,3,6-tri-O-benzyl-β-D-glucopyranoside (18), removal of the O-acetyl and N-phthaloyl group followed by N-acetylation. Condensation of 13 with 20 using trimethylsilyl trifluoromethanesulfonate afforded the desired pentasaccharide 21, which was transformed by removal of the benzyl group, O-acetylation, removal of the 2-(trimethylsilyl)ethyl group and imidate formation into the pentasaccharide donor 24. Glycosylation of (2S,3R,4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol (25) with 24 gave the desired β-glycoside 26, which was transformed into the four target compounds, via reduction of the azido group, coupling with octadecanoic acid or tetracosanoic acid, selective removal of the levulinoyl group, O-sulfation, hydrolysis of the methyl ester group and O-deacylation.