Anti-inflammatory activity of heterocyclic systems using abietic acid as starting material

A series of pyridines, pyrimidinone, oxazinones, and their derivatives were synthesized as anti-inflammatory agents using abietic acid (7-isopropyl-1,4a-dimethyl-1,2,3,4,4a,4b,5,6,10,10a-decahydrophenanthrene-1-carboxylic acid) as the starting material. The arylidiene derivative was treated with cyanothioacetamide to give cyano pyridine-thione, which was reacted with ethyl chloroacetate to yield the corresponding cyano ester. The ester was hydrolysed to the sodium salt, which was reacted with acetic anhydride to afford 2-methyloxazinone, which was treated with ammonium acetate to afford 2-methylpyrimidinone followed by methylation with methyl iodide to yield 2,3-dimethyl- pyrimidinone. In addition, the oxazinone derivative was reacted with aniline or hydrazine hydrate to give 3-phenyl- or 3-aminopyrimidinones. The latter reacted with thiophene-2-carboxaldehyde or phenylisothiocyanate to afford Schiff’s bases or thiosemicarbazide derivatives. The pharmacological screening showed that many of these compounds have good anti-inflammatory activity comparable to Prednisolone^® as reference drug.     

Umsetzung von 1,5-Dimethyl-2,3,3,4-tetrachlor-1,5,2,4-diazadiphosphorinan-6-on mit Anilinderivaten,Heptamethyldisilazan und tert.-Butylamin: Oxidative Addition von Tetrachlor-o-benzochinon an einige P(III)-haltige Produkte

The reaction of the title compound 1 with the p-R-aniline derivatives (R═H, F, OCH₃, NO₂, and NH₂) led to the formation of the aza-2σ³,4σ³-diphosphetidines 2a– 2e, whereas 2-trimethylsiloxyaniline furnished the azadiphosphetidine 2f. The reaction of the sterically crowded 2,6-dimethylaniline with 1 furnished the disubstituted derivative 3. The tricyclic compound 5 was formed during the reaction of 1,2-phenylenediamine with 1. Heptamethyldisilazane formed the aza-2σ ³ ,4σ ³ -diphosphetidine 6 on reaction with 1. The bulkier tert.-butylamine formed with 1 a mixture of the aza-2,4-diphosphetidine 7a and the disubstituted derivative 7b, which could not be separated. The reaction of 2b and 6 with tetrachloro-o-benzoquinone resulted in the formation of the bis-spirophosphoranes 8 and 9b, respectively. The formation of the monospirophosphorane 9a was observed in the ³¹P NMR spectrum. The characterization of compounds is based in particular on NMR investigations (¹H, ¹³C, ³¹P). 2a was characterized by a single-crystal X-ray structure analysis. The dimethylurea fragment is planar; the four-membered ring is folded about the P···P vector by 38.7°.     

Synthesis and antitumor activity evaluation of some novel pyrazolotriazine derivatives

6-Aminopyrazolo[1,2-a][1,2,4]triazine-4,8-dione derivative 3 was obtained upon the reaction of the acid hydrazide derivative 2a with ethyl cyanoacetate. The reactions of 3 with several electrophiles such as aldehydes, isatin, acetic anhydride, phenyl isocyanate, benzoyl isothiocyanate, and p-toluenesulfonyl chloride were studied. The structures of the newly synthesized compounds were established on the basis of IR, ¹H NMR, mass spectra, and elemental analyses. The antitumor activities of some selective compounds were examined against two cell lines as liver carcinoma cell line (HEPG-2) and human breast cancer cell line (MCF7).     

Reactivity of Z- and E-isomers of 2-benzamido-3-phenylacrylohydrazide towards some carbon electrophiles. A comparative study

Z- and E-isomers of 2-benzamido-3-phenylacrylohydrazide 2a, 2b have different relative reactivities towards some carbon electrophiles had been discussed.The Z-isomer underwent cyclization to give imidazole derivative 3 and triazine derivative 4, whereas the latter E-isomer does not undergo such cyclization. The reaction of 2a and/or 2b with 1,2-dibenzylidene hydrazine at different reaction conditions afforded the Schiff bases 6, 8 and the triazolidine derivative 9. Reactions of 2a, 2b with formic acid and phthalic anhydride gave the different cyclization products 10–14, respectively. The structures of all the new synthesized compounds were established from their IR, ¹H-NMR and mass spectra as well as elemental analyses.     

2-[3-(Trifluoromethyl)phenyl]furo[3,2-b]pyrroles: synthesis and reactions

The synthesis and reactions of methyl 2-[3-(trifluoromethyl)phenyl]-4H-furo[3,2-b]pyrrole-5-carboxylate (1a) are described. Upon reaction with methyl iodide, benzyl chloride, or acetic anhydride, this compound gave N-substituted products 1b-d. By hydrolysis of compounds 1a-c, the corresponding acids 2a-c were formed, or by reaction with hydrazine-hydrate, the corresponding carbohydrazides 3a-c were formed. By heating 2-[3-(trifluoromethyl)phenly]-4H-furo[3,2-b]pyrrole-5-carboxylic acid (2a) in acetic anhydride, 4-acetyl-2-[3-(trifluoromethyl)phenyl]furo[3,2-b]pyrrole (4) was formed. By hydrolysis of 4, 2-[3-(trifluoromethyl)phenyl]-4H-furo[3,2-b]pyrrole (5a) was formed, and reactions with methyl iodide or benzyl chloride gave N-substituted products 5b-c. The reaction of 4 with dimethyl butynedioate gave substituted benzo[b]furan 6. Compound 3a reacted with triethyl orthoesters giving 7a-c, which afforded with phosphorus (V) sulphide the corresponding thiones 8a-c. The thiones 8a-c reacted with hydrazine hydrate to form hydrazine derivatives 9a-c. The reaction of triethyl orthoformiate with compounds 9a-c led to furo[2′,3′: 4,5]pyrrolo[1,2-d][1,2,4]triazolo[3,4-f][1,2,4]triazines 10a-c. Hydrazones 11a-c were formed from 3a-c and 5-[3-(trifluoromethyl)phenyl]furan-2-carboxaldehyde. The effect of microwave irradiation on some condensation reactions was compared with “classical” conditions. The results showed that microwave irradiation shortens the reaction time while affording comparable yields.     

Improved methods of obtaining Nim-trityl-substituted histidine derivatives

Two variants are proposed for the synthesis of N^α-Boc-N^im-tritylhistidiine. The first variant starts from N^α,N^im-di-Boc-histidine, from which the N^im-Boc group is removed with hydrazine hydrate. The N^α-Boc-histidine formed is esterified with chlorotrimethylsilane, tritylated in the imidazole group, and, after the elimination of the trimethylsilyl protection from the carboxyl group, N^α-Boc-N^im-tritylglycine is obtained with a yield of 80%. The second variant starts from N^α,N^im-ditritylhistidine, which, by treatment with hydrochloric acid in acetone and then with dilute ammonia, is converted into N^im-tritylhistidine. From this, by acylation with di-tert-butyl pyrocarbonate, N^α-Boc-N^im-tritylhistidine is obtained with a yield of 91%. The acylation of N^im-tritylhistidine with other alkoxycarbonylating reagents leads to N^α-tert-amyl-, N^α-benzyl-, and N^α-4-methoxybenzyloxycarbonyl derivatives of N^im-tritylhistidine.     

Crown-ether styryl dyes

The surface enhanced Raman scattering (SERS) spectra of styryl dyes containing a crown-ether group and a heteroaromatic residue with sulfoalkyl (1a) or alkyl (1b)N-substituent and of their complexes with Mg²⁺ cations were recorded in the 10^–4–10^–8 mol L^–1 concentration range. A model for the interaction of compoundsla,b with a silver surface during their adsorption on an electrochemically treated electrode was suggested. Fastcis-trans relaxation of the adsorbed molecules1a,b and complexes (1a,b)Mg²⁺ was found. It was shown that at [1a] = 10^–5 mol L^–1 and moderate molar ratios (C _Mg/[1a] = 3/1 to 9/1) in acetonitrile solutions, (trans-1a)Mg²⁺ complexes are joined into head-to-tail type dimers. An excess of Mg²⁺ cations (C_Mg/[1a] > 100) leads to dissociation of the dimers yielding (trans-1a)(Mg²⁺)₂ complexes. The formation of dimers from complexes (trans-1a)Mg²⁺ is accompanied by a substantial distortion of the planar structure oftrans-1a. This may be an important factor influencing the efficiency of photocycloaddition involving dimers of (trans-1a)Mg²⁺.For part 15, see Ref. 1.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2429–2436, December, 1995.The work was carried out with financial support of the Russian Foundation for Basic Research (Project No. 94-03-08760) and, to some extent, of INTAS (Grant No. 93-1829) and of the International Science Foundation (Grant No. MHAOOO).     

Nα,Nim-di-tert-alkoxycarbonyl derivatives of histidine

The acylation of histidine with di-tert-butyl and di-tert-amyl pyrocarbonates has given the corresponding N,N_im-di-tert-alkoxycarbonyl derivatives. The N,N^im-di-tert-butoxycarbonyl derivative was obtained in the crystalline form by crystallization from benzene or carbon tetrachloride, or in the form of salts with cyclohexylamine, dicyclohexylamine, and diethylamine. N,N^im-di-tert-amyloxycarbonyl-histidine was characterized in the form of the salt with dicyclohexylamine.Institute of Biological and Medicinal Chemistry, Academy of Medical Sciences of the USSR, Moscow. Translated from Khimiya Prirodnykh Soedinenii, No. 3, pp. 379–383, May–June, 1980.     

Synthesis of 3-Substituted Pyrazole Derivatives by Mixed Anhydride Method and Study of Their Antibacterial Activities

A convenient synthesis of 3-substituted pyrazole derivatives by a mixed anhydride method using i-butylchloroformate and N-methylmorpholine at ?20 °C in tetrahydrofuran and study of in vitro antibacterial activities of the prepared compounds against Staphylococcus epidermidis, Bacillus subtilis, Pseudomonas aeruginosa, and Proteus valguris by agar-diffusion method were carried out. The results suggested that the products 4a, 4b, and 4c exhibited moderate to feeble inhibition against all test bacteria at greater concentration but 4d was best against Staphylococcus epidermidis (22 mm) and worst against Pseudomonas aeruginosa (16 mm) at the greatest concentration (2.5 mg/ml), and the activities decreased with decrease in concentration.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.]     

A 2-D CdI2 coordination network with 7-oxabicyclo[2.2.1]-5-heptene-2,3-dicarboxylate: synthesis,crystal structure,and luminescent properties

The in situ reaction of Cd(ClO₄)₂·6H₂O with 7-oxabicyclo[2.2.1]-5-heptene-2,3-dicarboxylic anhydride in the presence of lithium hydroxide affords a 2-D Cd^II coordination polymer, [Cd(L)(H₂O)]_∞ (1) (L?=?7-oxabicyclo[2.2.1]-5-heptene-2,3-dicarboxylate), which exhibits an unusual (3,6)-connected (4⁶.6⁶.8³)(4³)₂ CdI₂-type topology. The luminescent and thermal properties of 1 were investigated.     

Rapid and Sensitive Analysis of Diclofenac in Human Plasma by GC/SIM/MS

ABSTRACT

An analytical method for the determination of diclofenac with tolfenamic acid as the internal standard was developed and validated in human plasma by capillary gas chromatography-mass spectrometry (GC/MS). After the addition of the internal standard, the compounds were extracted from plasma at acidic pH into diethylether, which was then evaporated to dryness. The compounds were derivatized with pentafluoropropionic anhydride (PFPA) and a mixture (1000:2:3, v/w/w) of N-methyl-N-trimethylsilyltrifluoroacetamide (MSTFA), ammonium iodide (NH₄I), and dithioerythritol (DTE). They were determined by GC/MS at m/z 349 (a molecular ion) for diclofenac and m/z 270 (a base ion) for tolfenamic acid. The recovery of this procedure was 97.8%, and the linearity for calibration was 0.9907 as the coefficient factor. The detection and quantitation limits were 0.1 and 0.5 ng/mL, respectively.     

An expedient route for the reduction of carboxylic acids to alcohols employing 1-propanephosphonic acid cyclic anhydride as acid activator

A simple and efficient method for the synthesis of alcohols from the corresponding carboxylic acids is described. Activation of carboxylic acid with 1-propanephosphonic acid cyclic anhydride (T3P) and subsequent reduction using NaBH₄ yield the alcohol in excellent yields with good purity. Reduction of several alkyl/aryl carboxylic acids and N^α-protected amino acids/peptide acids as well as N^β-protected amino acids was successfully carried out to obtain corresponding alcohols in good yields. All the products were fully characterized by ¹H NMR and mass spectral analyses. The procedure is mild, simple and the isolation of the products is easy.     

Synthetic Studies on Tumor-Associated Antigens: Efficient Syntheses of Lea and Sialyl-Lea Oligosaccharides,and Their Deaminated Analogs1

ABSTRACT

Efficient syntheses of tumor-associated Le^a, sialyl Le^a and their deaminated analogs are described. The suitably protected D-glucosamine (4) or D-glucose (5) derivative was successively coupled with the methyl-1-thioglycosides (glycosyl donors) of D-galactose (6) and L-fucose (11) in high yields by using N-iodosuccinimide/trifluoromethanesulfonic acid (NIS/TfOH) as the glycosyl promoter. The resulting trisaccharides (12 and 13) were each converted, by deprotections, to the Le^a determinant (17) and its deaminated analog (18), and by further glycosylation with the phenyl-2-thioglycoside of N-acetylneuraminic acid (25), to the sialyl-Le^a determinant (30) and its deaminated analog (31), respectively.     

Catalyst-Free,Direct, High Regio- and Chemoselective Conversion of Epoxides to Vicinal Haloesters Under Mild,Neutral, and Solvent-Free Conditions

Abstract

A catalyst-free, high regio- and chemoselective method is described for the mild conversion of wide varieties of epoxides directly to their corresponding vicinal haloesters using quaternary ammonium halides R₄N⁺X^- (X equals; Cl, Br, I; R = n-butyl, n-pentyl, n-hexyl) in the presence of an aliphatic or aromatic carboxylic anhydride at room temperature under neutral and solvent-free conditions.     

Double-armed and tetra-armed cyclen-based cryptands

Double-armed and tetra-armed cyclen-based cryptands (1a–1d and 2) that bridge two aromatic rings by diethyleneoxy and triethyleneoxy units were prepared. The CSI-MS of 1:1 mixtures ([Ag⁺]/[ligand]) indicated that these new cryptands form 1:1 complexes with Ag⁺. The log K values for the interaction between Ag⁺ and 2 was greater than those of 1a–1d, double-armed cyclens (3a–3c and 4), and tetra-armed cyclen (5). The Ag⁺-ion-induced ¹H NMR spectral changes suggest that the Ag⁺–π interactions of the Ag⁺ complexes with the cryptands (1a–1d and 2) are stronger than those in Ag⁺/double-armed and tetra-armed cyclens. To visualise the Ag⁺?π interactions, the isosurfaces of the LUMO and HOMOs of the Ag⁺ complexes were calculated at the B3LYP/3–21G(*) theoretical level. The LUMO of the Ag⁺ ion is distorted by interaction with the HOMOs of the aromatic side arms. The calculations reveal Ag⁺?π interactions between the Ag⁺ ion and the aromatic side arms, and these are shown graphically.     

Study on biodegradable polymers: synthesis and characterization of poly(DL-lactic acid-co-l-lysine) random copolymer

Poly(DL-lactic acid-co-l-lysine) (PLAL) random copolymer was obtained by copolymerization of amino acid-N-carboxy anhydride with lactic acid anhydrosulphite in the presence of an initiator. The structures of the poly(DL-lactic acid-co-ε-cbz-l-lysine) and PLAL were characterized by IR, ¹H-NMR, ¹³C-NMR and elemental analysis. Different initiators were used to initiate the ring-opening copolymerization. Good agreement between calculated and actual compositions was observed in most cases when using dibutylzinc as initiator. The solubility of PLAL was discussed.     

Crown-containing styryl dyes

Styryl dyes containing a crown ether group and a heteroaromatic moiety with a sulfoalkylN-substituent (1a,b) undergo photocyclodimerization in acetonitrile in the presence of Mg(ClO₄)₂ to give only the typeA isomer of cyclobutane derivative (2a,b). The photochemical regio- and stereoselectivity of the cycloaddition is explained by self-organization of thetrans-isomers of the styryl dyes upon complexation with the Mg²⁺ cations into dimers with a fixed mutual arrangement of multiple bonds.For part 7, see ref. 1.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1449–1452, August, 1993.     

四-(p-羟基苯基)杯[4]间苯二酚芳烃的烃基化和酰胺化反应

间苯二酚和对羟基苯甲醛在盐酸/乙醇中缩合生成四-(p-羟基苯基)杯[4]间苯二酚芳烃(1), 在K₂CO₃/丙酮体系中将1分别与溴乙酸乙酯、溴丙烯、N,N-二丙基氯乙酰胺反应可得到全氧烃基化产物2a～2c. 含有12个乙氧基羰基甲氧基支链的2a被苯乙胺、N,N-二甲基二丙胺或三乙烯四胺直接胺解生成杯[4]间苯二酚芳烃酰胺衍生物3a～3c. 2a经过碱性水解、酰氯化、胺化反应转化为含吡啶基的酰胺衍生物3d. 化合物结构都用¹H NMR, IR和元素分析等方法进行了表征.     

超分子自组装合成杯[4]芳烃黄原酸镍(Ⅱ)配合物

利用二维和三维的大环及笼状主体分子与金属离子直接进行自组装反应合成新型有机无机杂化分子是当前超分子领域的研究热点之一。这类分子不仅具有新奇的光、电、磁等特性，而且还可作为新型的主体分子在客体识别、催化、吸附与分离等方面有广阔的应用前景。杯芳烃是有机超分子领域广受     

Diorganotin Complexes with N(4)-Phenylthiosemicarbazones: Synthesis,Spectroscopic Characterization,and Antibacterial Activity

Abstract

The organotin(IV) complexes, SnPh₂L^a (1), SnMe₂L^a (2), SnBu₂L^a (3), SnPh₂L^b (4), SnMe₂L^b (5), SnPh₂L^c (6), SnMe₂L^c (7), and SnBu₂L^c (8) were obtained by reaction of SnR ₂Cl₂ (R = Ph, Me, and Bu) with 1-(5-bromo-2-hydroxybenzylidene)-4-phenylthiosemicarbazide (H₂L^a), 1-((2-hydroxynaphthalen-1-yl)methylene)-4-phenylthiosemicarbazide (H₂L^b), and 1-(2-hydroxy-3-methoxybenzylidene)-4-phenylthiosemicarbazide (H₂L^c). The synthesized complexes have been investigated by elemental analysis, IR, ¹H NMR, and ¹¹⁹Sn NMR spectroscopy. The data show that the thiosemicarbazone acts as a tridentate dianionic ligand and coordinates via the thiol group, imine nitrogen, and phenolic oxygen. The coordination number of tin is 5. The in vitro antibacterial activities of the ligands and their complexes have been evaluated against Gram-positive (Bacillus subtilis and Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria and compared with the standard antibacterial drugs.

[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 following free supplemental files: Additional figures and tables]