Design and Synthesis of New Bile AcidSterol Conjugates Linked via 1,2,3‐Triazole Ring

A new steroid conjugates have been obtained from bile acids and sterol derivatives using ‘click chemistry’. Intermolecular 1,3‐dipolar cycloaddition of the propargyl ester of bile acids (lithocholic, deoxycholic, and cholic acid) and azide derivatives of sterols (ergosterol and cholesterol) gave a new bile acid? sterol conjugates linked with a 1,2,3‐triazole ring. The structures of all products were confirmed by spectroscopic (¹H‐ and ¹³C‐NMR, and FT‐IR) analyses, mass spectrometry (ESI‐MS), and in silico biological activity evaluation methods (PASS), as well as PM5 semiempirical methods.     

微波辐射下5-取代-2-硫代海因衍生物的合成

微波辐射下, 由硫氰酸铵与α-氨基酸通过两步反应合成了11种5-取代-2-硫代海因衍生物, 并用¹H NMR, IR和元素分析确证了中间产物和终产物的结构. 对比常规加热方法, 微波辐射具有反应时间短(4 min), 每步反应产率高(85%～93%)的优点. 同时对合成化合物2h的反应历程进行了讨论.     

Synthesis of novel phthalazine derivatives as pharmacological activities

Phthalazine derivatives attached to amino acid derivatives were synthesized with high yields. The reaction of phthalazine derivatives with different phthalyl and tosylamino acids such as glycine, alanine, phenylalanine, valine, serine, and threonine in the presence of N,N-dicyclo hexylcarbodiimide (DCC) as a dehydrating agent reagent yielded high yields of the afforded compounds. Phthalylamino acids derivatives were obtained by deprotection of phthalazine derivatives, with the latter heating with hydrazine hydrate. The chemical structures of all phthalazine derivatives were affirmed by elemental analysis and spectral data (IR, MS, ¹HNMR, and ¹³C NMR). Screening out and estimation of the synthesized derivatives for their cytotoxic and antioxidant activity were done, and most of them showed powerful activity in comparison with standard drugs.     

Synthesis and Characterization of Amino Acid Modified Chitooligosaccharides

Amino acid modified chitooligosaccharides were synthesized by the new synthetic route. The chloroacetyl-chitooliogosaccharide intermediates were prepared under a mild condition via a reaction between chitooligosaccharide (COS) and chloroacetic anhydride. The intermediates were subsequently reacted with a variety of amino acids, e.g., glycine, aspartic acid, alanine, arginine, and serine, under a basic condition, yielding amino acid modified COS products. The degree of chloroacetylation was calculated based on new ¹H NMR absorption peaks at 3.80 and 3.94 ppm, corresponding to  NH CO CH₂ Cl and  O CO CH₂ Cl, respectively. The degrees of chloroacetylation determined were 0.40, 0.44, 0.62, and 0.93 when the mole ratios of chloroacetic anhydride to COS were 0.5, 1, 2, and 4, respectively. The chemical structures of the COS derivatives were also determined using ¹H NMR spectroscopy. The biological properties of the derivatives were evaluated. Cytotoxicity of the derivatives was assessed by a direct contact, using L929 cells. An MTT assay was a method of choice to evaluate the efficacy of the derivatives to enhance the proliferation of L929 cells.     

Synthesis of New Thienopyridine Derivatives by a Reaction of 4‐(Methylsulfanyl)‐6,7‐dihydrothieno[3,2‐c]pyridine with Amino Acids

New thienopyridine derivatives were synthesized by the reaction of 4‐(methylsulfanyl)‐6,7‐dihydrothieno[3,2‐c]pyridine ( 5 ) with amino acids. The use of β‐amino acids led to thienopyridopyrimidone derivatives ( 9a–g ). Using α‐amino acids, such as glycine and racemic alanine under the same reaction conditions, compounds with two thienopyridine units were obtained. The structure of the novel compounds was confirmed by IR, ¹³C, and ¹H NMR spectroscopy, as well as mass spectrometry, along with single crystal X‐ray analysis. © 2013 Wiley Periodicals, Inc. Heteroatom Chem 24:124–130, 2013; View this article online at wileyonlinelibrary.com . DOI 10.1002/hc.21073     

Design and Synthesis of p/m-[p-（un）Substituted Phenylsulfonamido]phenyl β-Diketo Acids and Quinoxalone Derivatives

Diketo acid derivatives are potent and selective HIV-1 integrase inhibitors. To investigate the detailed synthesis of those derivatives, a series of p/m-[p-（un）substituted phenylsulfonamido]phenyl β-diketo acid derivatives have been designed and synthesized. The quinoxalone derivatives as the potential bioisosteres of the biologically labile β-diketoacid pharmacophores have also been synthesized from reactions of the corresponding diketo acids with o-phenylenediamine. The structures of all diketo acid （ester） and quinoxalone derivatives were confirmed by 1^H NMR, 13^C NMR, IR, HRMS and/or MS （ESI）. X-ray crystallographic analysis of 11b demonstrates a similar arrangement of the side chain of quinoxalone derivatives with the parent diketoacids due to the intramolecular hydrogen bond （O…H-N） and the sp^2 hybridization configuration of the two nitrogen atoms of the quinoxalone ring.     

Preparation of novel symmetrical bistetrazole-carbazole derivatives through a one-pot Ugi-azide reaction

A series of new symmetrical tetrazole-based carbazole derivatives starting from the initially generated 3,6-diformyl-N-alkylcarbazoles were successfully synthesized through a one-pot Ugi-azide reaction in moderate to high yields. Simplicity, easily accessible chemicals, mild reaction conditions, and fast separation of the products with the formation of bistetrazole-based carbazole derivatives in one step are some advantages of this method. The structure of the products was characterized and confirmed by using spectroscopic techniques such as ¹H NMR, ¹³C NMR, FT-IR, and MS spectroscopy.     

Bromination of N,N'-Substituted Malonodiamides

Aiming at preparation of biologically active compounds a bromination of N,N'-substituted malonodiamides in a glacial acetic acid was carried out. The use of one equiv of bromine provided monobromo derivatives, with two equiv of bromine dibromo-substituted products were obtained. Among the N,N'-dibenzylamides of alkylmalonic acids only the methyl homolog underwent bromination. The structure of compounds was proved by IR and ¹H NMR spectroscopy. The effect of the compounds synthesized on the central nervous system was investigated.     

Design,synthesis and application of new bile acid ligands with 1,2,3-triazole ring

New dimers have been obtained from propargyl ester of bile acids and α,α′-diazide-m-xylene by intermolecular 1,3-dipolar cycloaddition. These compounds have been used as ligands to form intermolecular hydrogen bonds with various aromatic acids. The structures of all products were confirmed by spectroscopic (¹H NMR, ¹³C NMR and FT-IR) analysis, mass spectrometry (ESI, MALDI) and PM5 semiempirical methods.     

Synthesis of some oxazolo and oxazinopyrano[3,2-c]quinolines and their antitumor activity

3-Amino-4-hydroxy-6-phenylpyrano[3,2-c]quinoline-2,5(6H)-dione was produced by a smooth reduction of its nitro precursor. Reaction of this 3-amino-4-hydroxypyranoquinoline derivative with different electrophiles, leading to a variety of oxazolo and oxazinopyrano[3,2-c]quinoline derivatives, was described. The structure of the new products was elucidated via elemental analysis, IR, ¹H NMR, ¹³C NMR, and mass spectra. Also, screening the antitumor activity of new compounds against two human cell lines (HepG-2 and HCT-116) was carried out. Some new products showed significant antitumor activities.     

Copper-immobilized ionic liquid as an alternative to organic solvents in the one-pot synthesis of bioactive dihydropyrano[2,3-c]pyrazole derivatives

In this study, a novel Cu-immobilized ionic liquid (IL)was designed, characterized, and employed as both promoter and solvent in the synthesis of some dihydropyrano[2,3-c]pyrazoles. The synthesized ionic liquid was characterized by ¹H NMR, ¹³C NMR, FTIR, ICP and EDX analysis and showed high catalytic activity to proceed the synthesis of bioactive dihydropyrano[2,3-c]pyrazole derivatives. This method has the advantage of using the IL as a green medium for the synthesize of the products in high to excellent yields within short reaction times.     

Synthesis,Structure, and Transformations of New Endic Anhydride Derivatives

4-Azatricyclo[5.2.1.02,6]dec-8-ene and its N-phenyl derivative were synthesized by reaction of endic anhydride with amines, transformation of the amido acids thus obtained to imides, and subsequent reduction of the latter with lithium aluminum hydride. The unsubstituted tricyclic amine was brought into reactions with electrophilic reagents: p-toluenesulfonyl chloride, p-toluoyl chloride, m-tolyl isocyanate, phenyl isothiocyanate, and endic anhydride to obtain a number of new derivatives; also, the corresponding salt with 1-adamantanecarboxylic acid was isolated. N-(p-Tolylsulfonyl)- and N-(m-tolylcarbamoyl)-4-azatricyclo-[5.2.1.02,6]dec-8-enes were oxidized to the corresponding 8,9-epoxy derivatives with monoperoxyphthalic acid. The structure of the products was confirmed by the data of IR, ¹H and ¹³C NMR, and mass spectra. The molecular structures of N-(p-iodophenyl)bicyclo[2.2.1]hept-2-ene-endo-5,endo-6-dicarboximide and N-phenyl-4-azatricyclo[5.2.1.02,6]dec-8-ene were established by X-ray analysis.     

Chemical Modification of Plant Alkaloids. 2. Reaction of Cotarnine with Barbituric Acid Derivatives and Structure of 5-Dihydrocotarnylbarbituric Acids

The reaction of barbituric acid and its N-substituted derivatives and 2-thio analogs with cotarnine forms 5-(4-methoxy-6-methyl-5,6,7,8-tetrahydro-2H-1,3-methylenedioxy-[4,5-g]isoquinolinyl-1)barbituric acids, a new class of zwitter-ions, the structure of which was studied by ¹ H and ¹³ C NMR spectroscopy and mass spectrometry. The prepared compounds exist in solution as stable intermolecular associates and have a complicated H-bonded structure.     

GLC-MS analysis of the fatty acids of the seed oil,triglycerides, and cyanolipid of Paulliania elegans (Sapindaceae) – a rich source of cis-13-eicosenoic acid (paullinic acid)

The fatty acids of the total lipids, triglycerides, and the cyanolipid of Paullinia elegans (Sapindaceae) have been analyzed as their methyl esters and 4,4-dimethyloxazoline derivatives by gas chromatography-mass spectrometry. It was shown that the gas chromatographic separation of the oxazoline derivatives was sufficient to ensure the correct identification of the monoenic fatty acid positional isomers. Stereochemistry of the double bonds has been confirmed by infrared and ¹³C-nuclear magnetic resonance (NMR) spectroscopy. cis-13-Eicosenoic Acid (Paullinic acid) (44.4%) and cis-11-octadecenoic acid (cis-vaccenic acid) (19.8%) were found to be the main components beside other monoenoic acid positional isomers. The cyanolipid of P. elegans was identified as 2,4-dihydroxy-3-methylenebutyronitrile derivative by IR, ¹H-NMR, ¹³C-NMR spectroscopy and was quantified by ¹H-NMR spectroscopy (71.4%).     

Synthesis of tri-n-butyltin taurocholate,taurodeoxycholate and glycocholate

The bile acids, taurocholic, taurodeoxycholic and glycocholic acid, were reacted with bis(tri-n-butyltin) oxide (TBTO) to form 1:1 derivatives. The water of reaction was removed with 2, 2-dimethoxypropane or by azeotropic distillation with benzene. The compounds were characterized by ¹³C and ¹¹⁹Sn NMR, IR, elemental analysis, molecular weight determination, DTA, TGA, and conductance measurements. The data indicated that tri-n-butyltin glycocholate forms a covalent ester, tin being tetracoordinated. The taurocholic and taurodeoxycholic acid derivatives contain one molecule of coordinated water. They partially dissociate in polar solvents. The taurocholic and glycocholic acid derivatives were tested in vitro as anticancer agents and exhibited ED₅₀ in the 0.2–0.4 ppm (mg kg^?1) range against KB epidermoid tumor and P-388 leukemia using NCI protocols.     

Synthesis and Herbicidal Evaluation of 4,6‐Dimethoxyaurone Derivatives

A multi‐step synthesis of 4,6‐dimethoxyaurone derivatives was carried out from phloroglucinol and chloroacetonitrile, and the products were characterized by ¹H NMR, ¹³C NMR, and HRMS. The preliminary bioassays showed that some products exhibited herbicidal activity against dicotyledonous plant Brassica campestris L.     

A Precautionary Note Regarding Derivatization Of Secondary Amines With Dialkyeacetals Of Formamide Other Than The Diethyl Derivative A Correction

Abstract

In an earlier communication we reported GC-MS studios on the reaction products of secondary amino tricyclics and dimethylformamide. ¹ The diethyl acctal reaction products were identified as N-ethyl derivatives on the basis of mass spectroscopic analysis. In a follow-up study, we reported the same reaction products were formed from other DMF-dialkyl acetals, such as dimethyl and dipropyl acetals. ² In view of this unusual reaction we reinvestigated the structure of the reaction products utilizing alternative spectroscopic methods, viz. NMR and IR, and present a correction to our earlier work ()Desipramine (1 mg) was heated with DMF-diethyl acetal (100 μ 1) at 80°C. for 15 min. The product: was dissolved in ethyl acetate (5 ml), extracted into 1 ml of 0.5 N HCl and back extracted into ethyl acetate at pH 11.0. The organic extract was dried over anhydrous sodium sulfate and evaporated to dryness under nitrogen. The resulting residue was used directly in the NMR and IR studies.     

Simultaneous determination of phenolic compounds and triterpenic acids in oregano growing wild in Greece by 31P NMR spectroscopy

³¹P nuclear magnetic resonance (NMR) spectroscopy was used to detect and quantify simultaneously a large number of phenolic compounds and the two triterpenic acids, ursolic acid and oleanolic acid, extracted from two oregano species Origanum onites and Origanum vulgare ssp. Hirtum using two different organic solvents ethanol and ethyl acetate. This analytical method is based on the derivatization of the hydroxyl and carboxyl groups of these compounds with the phosphorous reagent 2‐chloro‐4,4,5,5‐tetramethyl‐1,3,2‐dioxa phospholane and the identification of the phosphitylated compounds on the basis of the ³¹P chemical shifts. Unambiguous assignment of the ³¹P NMR chemical shifts of the dihydroxy‐ and polyhydroxy‐phenols in oregano species as well as those of the triterpenic acids was achieved upon comparison with the chemical shifts of model compounds assigned by using two‐dimensional NMR techniques. Furthermore, the integration of the appropriate signals of the hydroxyl derivatives in the corresponding ³¹P NMR spectra and the use of the phosphitylated cyclohexanol as an internal standard allowed the quantification of these compounds. The validity of this technique for quantitative measurements was thoroughly examined. Copyright © 2012 John Wiley & Sons, Ltd.     

Reactions of Heteroaryl Substituted Propenones

Thienyl- and furylpropenones reacted with malonates, cyanoacetates, and malononitrile giving addition products which could be cyclized to heteroaryl substituted dihydropyranes, cyclohexanols, and piperidones. Heteroaryl substituted cyclopropyl ketones were prepared by reactions with Me₃SO⁺ I⁺, and by reaction with Lewis acids they were transformed into substituted dihydrobenzo[b]furanone or -thiophenone, or -hydroxy ketones. Cycloadditions with thiophene derivatives allowed the synthesis of substituted benzo[b]thiophene derivatives, but with poor yields. Structures and stereochemistry were established mainly by means of NMR spectroscopy.     

New steroid‐group‐containing borazine compounds and their 13C NMR spectra

New borazine compounds containing steroid units (cholesteryl and stigmasteryl) were prepared by the reactions of B,B′,B″‐trichloro‐N,N′,N″‐trimethylborazine with the 3‐chloro derivatives of the corresponding steroids under Grignard conditions. The products were characterized by ¹³C–¹H correlation NMR measurements to give fully assigned ¹³C NMR data. Copyright © 2001 John Wiley & Sons, Ltd.