SYNTHESIS AND CHEMISTRY OF SOME NEW 2-MERCAPTOIMIDAZOLE DERIVATIVES OF POSSIBLE ANTIMICROBIAL ACTIVITY

4,5-Diaryl-2,3-dihydro-2-mercaptoimidazoles (2a–e) were synthesized. They reacted with chloroacetic acid in gl. acetic acid/Ac ₂ O in presence of anhyd. sodium acetate afforded 5,6-diaryl-2,3-dihydro-imidazo[2,1-b]thiazol-3-ones (3a–d). Also these compounds were prepared by the action of chloroacetyl chloride on compounds (2) in pyridine. Compounds (3a–d) on condensation with aromatic aldehydes yield 2-arylmethylene-5,6-diaryl-2,3-dihydroimidazo[2,1-b]-thiazol-3-ones (4a–q). The latter compounds were prepared directly by the reaction of (2) with chloroacetic acid and the aromatic aldehydes. Compounds (3a–d) coupled with aryldiazonium salts in pyridine to give 2-arylhydrazono-5,6-diaryl-2,3-dihydroimidazo[2,1-b]thiazol-3-ones (5a–r). Also compounds (2) when reacted with 2 or 3-bromopropionic acid afford 2,3-di-hydro-5,6-diaryl-2-methylimidazo[2,1-b]thiazol-3-ones (6a–d) and 2,3-di-hydro-6,7-diaryl imidazo-[2,1-b]-1,3-thiazin-4-ones (7a–d), respectively. Compounds (3, 6, and 7) have been cleaved by aromatic amines to give the corresponding 2-(4′,5′-diaryl-2′,3′-dihydroimidazol-2′-yl)thioacetanilide (8a–f), 2-(2′,3′-dihydro-4′,5′-diaryl imidazol-2′-yl)thiopropionamide (9a–c), and 3-(2′,3′-dihydro-4′,5′-diaryl-imidazol-2′-yl)thiopropionamide (10a–d) respectively. All the prepared compounds show considerable antimicrobial activity against bacteria, yeast, and fungi.     

Introduction of a New Class of Ligands for the Metal-Catalyzed Enantioselective Synthesis

Protected thiosugars were prepared as ligands for the metal-catalyzed enantioselective synthesis. The protecting groups in these ligands were varied to test a proposed new concept for the metal-catalyzed enantioselective synthesis. This new concept centres on the use of a stair-like ligand with a large substituent on one side and a small substitutent on the other rather than the commonly employed ligands which have C₂ symmetry (see Fig.3). In such a ligand, both substituents should have a major influence on the coordination of a prochiral substrate. To test this proposal, 3-thio-α-D -glucofuranose derivatives with the following substituents were synthesized: 1,2-O-isopropylidene-5,6-O-methylidene (see 24 ), 1,2:5,6-di-O-isopropylidene (see 2 ), 5,6-O-cyclohexylidene-1,2-O-isopropylidene (see 23 ), 1,2-O-cyclohexylidene-5,6-O-isopropylidene (see 14 ), 1,2:5,6-di-O-cyclohexylidene (see 13 ), 5,6-O-(adamantan-2-ylidene)-1,2-O-isopropylidene (see 21 ), and 1,2:5,6-di-O-(adamantan-2-ylidene) (see 25 , Table 2). As a representative of the allofuranoses, 1,2:5,6-di-O-isopropylidene-3-thio-α-D -allofuranose ( 6 ) was chosen. The following derivatives of 1,2-O-isopropylidene-α-D -xylofuranose were also synthesized: 1,2-O-isopropylidene-5-deoxy-3-thio-α-D -xylofuranose ( 29 ), 1,2-O-isopropylidene-3-thio-α-D -xylofuranose ( 28 ) and 5-O-[(tert-butyl)-diphenylsilyl]-1,2-O-isopropylidene-3-thio-α-D -xylofuranose ( 15 , see Table 2). The proposed concept was tested using the copper-catalyzed 1,4-addition of BuMgCl to cyclohex-2-en-1-one. The enantioselectivity was very dependent on the ligand used and was up to 58%.     

Selective Protecting Method for the Individual Hydroxyl Groups of Kdn

ABSTRACT

Selective protection for the individual hydroxyl groups of methyl (phenyl 3-deoxy-2-thio-β-D-glycero-D-galacto-2-nonulopyranosid)onate (2) was examined. The 4-, 5-, and 7-hydroxyl groups of methyl (phenyl 3-deoxy-8,9-O-isopropylidene-2-thio-β-D-glycero-D-galacto-2-nonulopyranosid)onate (3) were found selectively to be protected by t-butyldimethylsilyl, methoxymethyl, and benzoyl groups, respectively. In order to obtain the 8- and 9-hydroxyl derivatives selectively, methyl (phenyl 4,5,7-tri-O-acetyl-9-O-t-butyldimethylsilyl-3-deoxy-2-thio-β-D-glycero-D-galacto-2-nonulopyranosid)onate (12) and methyl (phenyl 4,5,7,8-tetra-O-benzyl-9-O-triphenylmethyl-3-deoxy-2-thio-β-D-glycero-D-galacto-2-nonulopyranosid)onate (19) were prepared in moderate yields.     

Reaction of Triethyl Phosphonoacetate Anion with Phenylhydrazones: A New Method for the Preparation of 3(2H)-Pyridazinones

Various 5,6-disubstituted-2-phenyl-3(2H)-pyridazinones 4 have been synthesised by reacting triethyl phosphonoacetate anion with monophenylhydrazone of 1,2-dicarbonyl compounds 2.     

Contribution a l'Etude Electocimique de Derives de l'Acide Mercapto-2 Pyridinecarboxylique-5. I

Abstract

5-methoxycarbonoyl-1-methyl-2-thio-1,2-dihydropyridine and 1-metyl -2-thio-1,2-dihydropyridine-5-carboxylic acid heve been studied by recent electrochemical methods. The analysis of classical, alternative (A.C.) and pulse polarograms led to precise the nature of the observed currents. The pH variatiors and the supporting electrolyte modifications have an important influence on these currents.     

The cycloaddition reaction of 3,4-dimethyl-1-thio-1-phenylphosphole with tropone

3,4-Dimethyl-1-thio-1-phenylphosphole reacts, under elevated temperatures, with tropone to give two [4+2] isomeric adducts: Endo-syn-5,6-dimethyl-3-thio-3-phenyl-3-phosphatricyclo [5.3.2.0^2,6]dodec-4,8,11-trien-10-one (1) and Endo-anti-5,6-dimethyl-3-thio-3-phenyl-3-phosphatricyclo[5.3.2.0^2,6]dodec-4,9,11-trien-8-one (2). In addition to the endo-exo,syn-anti relationship the phosphorus configuration in 1, 2 and some derivatives was also elucidated by means of NMR-shift reagents and ²J_PH coupling constants.     

Preparation and lectin binding specificity of polystyrene particles grafted with glycopolymers bearing S-linked carbohydrates

Polystyrene particles bearing ATRP initiating groups, obtained by emulsifier-free emulsion polymerization of styrene (St) and 2-chloropropyloxyethyl methacrylate (CPEM), were subjected to surface-initiated activator generated by electron transfer for atom transfer radical polymerization (AGET ATRP) using glycomonomers, i.e., 4-vinylbenzenesulfonamidoethyl 1-thio-β-d-glucopyranoside (1) and 4-vinylbenzenesulfonamidoethyl 1-thio-β-d-lactoside (2). The glycopolymer-grafted polystyrene particles obtained Gp1 and Gp2 were shown to have hydrated graft layers of 15–65 nm in thickness on the cores of 370 nm in diameter. Gp1 and Gp2 coagulated in the presence of concanavalin A (Con A) and that of peanut agglutinin (PNA), respectively, showing highly specific response toward lectins.     

Synthesis and Molluscicidal Activity of Phosphorus-Containing Heterocyclic Compounds Derived from 5,6-Bis (4-bromophenyl)-3-hydrazino-1,2,4-triazine

Novel N¹-(phosphoryl moiety)-N²-(1,2,4-triazin-3-yl)hydrazines 4, 6, 8, 9 and 12, iminophosphorane 3, iminophosphane 5, 1,2,4-triazinyldiazaphospholine 7, 1,2,4,3-triazaphospholinotriazines 2, 10, 11, and 1,2,4-triazino[3,2-c][1,2,4,5] triazaphosphine 13 have been obtained via treatment 5,6-bis(4-bromophenyl)-3-hydrazino-1,2,4-triazine (1) with various polyfunctional phosphorus reagents by stirring at room temperature or refluxing for long time in tetrahydrofuran. Structures of these compounds have been deduced upon the basis of elemental and spectral data. Molluscicidal activity of the prepared compounds against Biomphalaria Alexandrina snails (the intermediate host of Schistosoma mansoni) showed considerable activities.     

Succinct and Facile Synthesis of Innovative Thiopyrimidines With Antimicrobial and Antitubercular Investigation

Abstract

To develop a series of bioactive heterocycles in minimum number of steps, 3-methyl- 4-(substituted phenyl)-1-phenyl-4,8-dihydropyrazolo[4′,3′:5,6]pyrano[2,3-d]pyrimidine-5,7 (1H,6H)-dithione 2(a–j), 4-(4-substituted phenyl)-5-imino-3-methyl-1,6-diphenyl-4,5,6,8-tetrahydropyrazolo[4′,3′:5,6]pyrano[2,3-d]pyrimidine-7(1H)-thione 3(a–j), and N-[4-(subs- tituted phenyl)-3-methyl-1-phenyl-7-thioxo-1,4,7,8-hexahydropyrazolo[4′,3′:5,6]pyrano[2,3-d]pyrimidine-5-yl]thiourea 4(a–j) have been synthesized from amino nitrile functionality 1(a–j). The structures of the compounds were elucidated by IR, ¹H NMR, elemental analysis, and some representative ¹³C NMR and mass spectra. All the title compounds were screened for antimicrobial and antitubercular activities, while some representative compounds were tested for antioxidant activity. Out of synthesized compounds, compounds 1j (4-CH₃), 2d (4-F), 4c (4-OH), and 4i (3-Br) exhibited maximum inhibition against Mycobacterium Tuberculosis H₃₇Rv. Compound 3c (4-OH) revealed elevated efficacy against all tested bacterial strain, while compounds 1i (3-Br), 2c (4-OH), and 3h (3-NO₂) were found efficacious against Candida albicans as compared to standard 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 free supplemental file.     

5,6-位烷氧基保护和3-/3,8-位三苯胺拓展1,10-菲咯啉衍生物与银离子识别

在1,10-菲咯啉的5,6-位引入烷氧基后,分子的反应活性明显提升,同时获得的三苯胺基(TPA)衍生物的溶解性也明显提高。晶体结构分析表明:烷氧基团是以六元环形式的乙撑二氧结构接入1,10-菲咯啉环的5,6-位。化合物TPA1和TPA2均对Ag+表现出选择性识别作用。其中,TPA1与Ag+作用后虽然荧光减弱不明显,但其发射波长明显红移(47 nm)。而TPA2和Ag+作用后,415和542 nm处荧光发射峰同时淬灭。化合物TPA3虽然也能与Ag+发生相互作用使荧光减弱,但是其荧光减弱幅度不大,很容易受到其它杂离子干扰影响,不适用于离子识别研究。     

5,6-位烷氧基保护和3-/3,8-位三苯胺拓展1,10-菲咯啉衍生物与银离子识别

在1,10-菲咯啉的5,6-位引入烷氧基后,分子的反应活性明显提升,同时获得的三苯胺基（TPA）衍生物的溶解性也明显提高。晶体结构分析表明：烷氧基团是以六元环形式的乙撑二氧结构接入1,10-菲咯啉环的5,6-位。化合物TPA1和TPA2均对Ag+表现出选择性识别作用。其中,TPA1与Ag⁺作用后虽然荧光减弱不明显,但其发射波长明显红移（47 nm）。而TPA2和Ag⁺作用后,415和542 nm处荧光发射峰同时淬灭。化合物TPA3虽然也能与Ag⁺发生相互作用使荧光减弱,但是其荧光减弱幅度不大,很容易受到其它杂离子干扰影响,不适用于离子识别研究。     

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 of new annulated pyridazine derivatives and studying their antioxidant and antimicrobial activities

Benzil was reacted with cyanoacetohydrazide under microwave irradiation to give 3-oxo-5,6-diphenyl-2,3-dihydropyridazine-4-carbonitrile 1 which used as starting material for the synthesis of new heterocyclic compounds. Chlorination of pyridazinone 1 with POCl₃ afforded the chloro-pyridazine derivative 3, which then condensed with 2-aminothiazole or hydrazine hydrate to produce 3,4-diphenyl-5H-thiazolo[3′,2′:1,2]pyrimido[4,5-c]pyridazin-5-one 5 or 3-hydrazinyl-5,6-diphenylpyridazine-4-carbonitrile 6, respectively. New Schiff bases were obtained by condensation reactions of compound 6 with different aldehydes. On the other hand, compound 6 reacted with different carbon electrophiles naming acetyl acetone, diethyl malonate, and phenyl isothiocyanate producing new pyarazolo-pyridazine derivatives 11, 12, and 14, respectively. Chemical structures of all newly synthesized compounds were confirmed on the basis of spectral data and had been screened for antimicrobial and antioxidant activity.     

Studies on the Thioglycosides of N-Acetylneuraminic Acid. 6: Synthesis of Ganglioside GM4 Analogs1

Abstract

Two kinds of ganglioside GM₄ thioanalogs having different fatty acyl groups at the ceramide moiety, (2S, 3R, 4E)-1-O-[3-S-(5-acetamido-3,5-di-deoxy-D-glycero-α-D-galacto-2-nonulopyranosylonic acid)-3-thio-β-D-galacto-pyranosyl]-2-octadecanamido (or -tetracosanamido)-4-octadecene-1,3-diol (12, 13), have been synthesized. Condensation of the trichloroacetimidate 7, derived from 1,2,4,6-tetra-O-acetyl-3-S-(methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-α-D-galacto-2-nonulopyranosylonate)-3-thio-β-D-galactopyranose (6) by selective 1-O-deacetylation and subsequent trichloroacetimidation, with (2S, 3R, 4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol (4), gave the coupling product (8), which was converted into the title compounds via selective reduction of the azide group, condensation with fatty acids, and removal of the protecting groups.     

Synthesis and Biological Activity of 4-Aryl-<Emphasis Type="Italic">N</Emphasis>-(5,6-R-benzo[<Emphasis Type="Italic">d</Emphasis>]thiazol-2-yl)- 2-hydroxy-4-oxobut-2-enamides

The interaction of 5-arylfuran-2,3-diones with 5,6-R-benzo[d]thiazole-2-amines has resulted in 4-aryl-N-(5,6-R-benzo[d]thiazol-2-yl)-2-hydroxy-4-oxobut-2-enamides. The products structure has been confirmed by means of IR, NMR, and ¹H NMR spectroscopy as well as mass spectrometry. Analgesic and antimicrobial activities of the prepared compounds have been studied; acute toxicity of the most active compounds has been determined. The relationship between the structure and biological activity of the obtained compounds has been elucidated. The compounds acting comparably or better than the reference drugs have been found.     

Molecular and crystal structure of 5,6-diamino-1-methyluracil and 5,6-diamino-1,3-dimethyluracil monohydrate. Semiempirical calculations (AM1 and PM3) on 5,6-diaminouracil derivatives

The crystal and molecular structures of 5,6-diamino-1-methyluracil and 5,6-diamino-1,3-dimethyluracil monohydrate have been determined from X-ray diffraction. Both compounds are planar and the two amino groups have two different conformations. The substituent at the 5 position seems to be a true primary amino group with a strongly sp³ nitrogen, whereas the one at the 6 position is nearly coplanar with the uracil ring, displaying a predominant sp² character.Semiempirical calculations were made on 5,6-diaminouracil, 5,6-diamino-2-thiouracil and their endocyclic N-methylated derivatives using the AM1 and PM3 hamiltonians. These indicate that the stability decreases on increasing methylation, the 2-thio compounds always being less stable than the 2-oxo ones.     

Isolation and characterization of 3,5,6-trihydroxy-carotenoids from petals ofLilium tigrinum

Summary Reinvestigation by HPLC of the petals ofLilium tigrinum and the isolation of some minor compounds is reported. Using HPLC-controlled, preparative-column chromatography, 5,6-diakarpoxanthin (6), 6-epikarpoxanthin (2), 5,6-diacapsokarpoxanthin (8), and 9Z-antheraxanthin (9Z-13) were isolated and characterized. Based on spectroscopic data the absolute configurations of6 and8 were identical with those originating from paprika, thus the 5,6-diakarpoxanthin (6) and 5,6-diacapsokarpoxanthin (8) have the 3S, 5S, 6S configuration and 6-epikarpoxanthin (2) has the 3S, 5R, 6S configuration. Presented at: Balaton Symposium on High-Performance Separation Methods, Siófok, Hungary, September 3–5, 1997.     

Studies on the Thioglycosides of N-Acetyl-Neuraminic Acid 8: Synthesis of S-(α-Sialyl)-(2→ 6)-β-Hexopyranosyl and -(2→ 6')-β-Lactosyl Ceramides Containing β-Thioglycosidically Linked Ceramide

ABSTRACT

Coupling of the sodium salt of S-(methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-α-galacto-2-nonulopyranosylonate)-(2→'6)-2,3,4-tri-O-acetyl-1,6-dithio-β-D-glucopyranose (5), -β-D-galactopyranose (8), or S-(methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-α-D-galacto-2-nonulopyranosylonate)-(2→'6)-O-(2,3,4-tri-O-acetyl-6-thio-β-D-galactopyranosyl)-(1→'4)-2,3,6-tri-O-acetyl-1-thio-β-D-glucopyranose (12), which were prepared from the corresponding 1-hydroxy compounds, 1, 2, and 9, via 1-chlorination, displacement with thioacetyl group, and S-deacetylation, with (2S,3R,4E)-2-azido-3-O-benzoyl-1-O-(p-toluenesulfonyl)-4-octadecene-1,3-diol (13), gave the corresponding β-thioglycosides 14, 18 and 22, respectively in good yields. The β-thioglycosides obtained were converted, via selective reduction of the azide group, condensation with octadecanoic acid, and removal of the protecting groups, into the title compounds.     

Thioglycosides as Potential Glycosyl Donors in Electrochemical Glycosylation Reactions. Part 2: Their Reactivity Toward Sugar Alcohols.

Abstract

Constant potential electrolysis of the glycosyl donors p-methylphenyl 2,3,4,6-tetra-O-benzyl-1-thio-β-D-glucopyranoside (1) and p-methylphenyl 3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-1-thio-β-D-glucopyranoside (4) in dry acetonitrile in the presence of various primary and secondary sugar alcohols, performed in an undivided cell, gave β-linked disaccharide derivatives selectively in good yields. Oxidative coupling of p-methoxyphenyl 2,3,4-tri-O-benzyl-1-thio-β-L-fucopyranoside (2 1) with p-methoxybenzyl 4,6-O-benzylidene-2-deoxy-2-phthalimido-β-D-glucopyranoside (16) gave selectively the α-linked disaccharide 22 in good yield.     

SYNTHESIS,SPECTRAL STUDIES,AND ANTIMICROBIAL ACTIVITIES OF [N-(UN)ALKYLATED-2-ARYLINDOL-3-YL]THIOCARBOXAMIDES

A series of [N-(un)alkylated-2-arylindol-3-yl]thiocarboxamides(6) have been synthesized by the condensation of alkyl [N-(un)alkylated-2-arylindol-3-yl]dithiocarboxylates (5) with appropriate secondary amines in absolute alcohol. Compound 5 was prepared by the reaction of N-(un)alkylated-2-arylindoles with carbon disulphide in the presence of potassium-t-butoxide followed by alkyl iodide under nitrogen atmosphere. All of the compounds have been characterized on the basis of their elemental and spectral data and have been screened for their antibacterial and antifungal activities. Some of the synthesized compounds have shown promising activity.