Chemistry of sulfonyl isocyanates and sulfonyl isothiocyanates. X. Possible routes to substituted imidazolidinethiones and hexahydropyrimidinethiones

4-Toluenesulfonyl isocyanate (I) reacted with 2-aminoethanol and 3-amino-l-propanol to give 2:1 isocyanate/amino alcohol addition products. 1-Amino-2-propanol and I gave 1:1 and 2:1 adducts while 2-amino-2-methyl-l-propanol afforded only a 1:1 adduct. 4-Toluenesulfonyl isothio-cyanate (III) gave 1:1 adducts with 2-aminoethanol, l-amino-2-propanol and 3-amino-l-propanol, the first two of which were cyclized by concentrated sulfuric acid to 1-(4-toluenesulfonyl)-imidazoline-2-thiones and the third to 1-(4-toluenesulfonyl)hexahydropyrimidine-2-thione. A 1:2 adduct was obtained from III and 2-amino-2-methyl-l-propanol. Amino acids reacted with I and with 4-chlorobenzenesulfonyl isocyanate (II) to give N-(arylsulfonyl)-N¹-(carboxylic acid)-ureas. N-(4-Toluenesulfonyl)-N¹-(acetic acid)-urea (XVI) was converted to the methyl ester (XIX) by concentrated sulfuric acid and methanol and to water-soluble unrecoverable products by sulfuric acid alone. Glycine and III gave N-(4-toluenesulfonyl)-N¹-(acetic acid)-thiourea (XX) which was converted to the methyl ester (XXII) by concentrated sulfuric acid/methanol and to the cyclic 1-(4-toluenesulfonyl)imidazolin-5-one-2-thione (XXI) by sulfuric acid alone.     

Synthesis, Mass Spectrometric Studies, and Biological Evaluation of 3,5-Dimethoxyhomophthalic Acid and Related Compounds

3,5-Dimethoxyhomophthalic acid was synthesized in four steps from 3,5-dimethoxycinnamic acid via a series of reactions including cyclization of 3-(3',5'-dimethoxyphenyl)propionic acid to 5,7-dimethoxy-1-indanone and oxidative decomposition of methyl-2-hydroxy-2-[5,7-dimethyoxy-1-oxo-1H-inden-2(3H)-ylidene]acetate to 3,5-dimethoxyhomophthalic acid.The synthesized compounds were characterized by elemental analysis,IR,1H NMR,and MS.The biological evaluation experiments of 3,5-dimthoxyhomophthalic acid and the related synthesized compounds were also carried out.Naturally occurring biologically active isocoumarins were prepared in a single step by the condensation of the homophthalic acid with appropriate acid chlorides.     

Diisophorone and related compounds—II: 1-Alkoxy- and 1-carboxy-diisophorane derivatives

The acid catalysed interaction in dioxan of trialkyl orthoformates with diisophor-2(7)-en-ol-3-one, diisophor-2(7)-en-ol, and their bisnor-homologues, provides the corresponding 1-alkoxy-compounds. Their structure is established by the identity of -methoxydiisophor-2(7)-en-3-one obtained by this method, and by the action of sodium methoxide on 1-chlorodiisophor-2(17)-en-3-one. The latter is regenerated from 1-methoxy(or ethoxy) diisophor-2(7)-en-3-one by the action of stannic chloride-acetyl chloride. Catalytic hydrogenation reduces the 3-keto-function in 1-alkoxydiisophor-2(7)-en-3-ones to a methylene unit; simultaneous removal of the 1-alkoxy-group in the case of the 1-isopropoxy-homologue yields the penultimate parent hydrocarbon of this series, diisophor-2(7)-ene.The combined action of silver sulphate and formic acid in concentrated sulphuric acid on 1-chlorodiisophor-2(7)-en-3-one (and its bisnor-homologue) produces the corresponding 1-carboxylic acids. These are also obtainable by the hydrolysis of the 1-cyano-compound, and are esterifiable by the standard methods.     

Synthesis and spectral studies of platinum complexes with amide-group containing ligands

Summary Complexes of platinum(II) with 2-(acetylamino)benzoic acid, 2-(benzoylamino)benzoic acid, maleanilic acid, malea-1-naphthanilic acid, 2-(phenylamino)benzoic acid, 2-[(2-aminophenylamino)carbonyl]benzoic acid, 2-(aminobenzoyl)benzoic acid, 2-[1-naphthalenylamino)-carbonyl]benzoic acid, 2-(2-aminobenzoylamino)-benzoic acid have been prepared and characterized by elemental analysis, molar conductivity measurements, thermal data and i.r., electronic and n.m.r. spectra.     

Enzymatic hydrolysis of alpha- and beta-oligo(L-aspartic acid)s by poly(aspartic acid) hydrolases-1 and 2 from Sphingomonas sp. KT-1

The enzymatic hydrolysis of alpha- and beta-oligo(L-aspartic acid)s by PAA hydrolase-1 and PAA hydrolase-2 (purified from Sphingomonas sp. KT-1) was performed to elucidate the mechanism of the microbial degradation by Sphingomonas sp. KT-1 of the thermally synthesized alpha,beta-poly(D,L-aspartic acid) (tPAA). GPC analysis of the hydrolyzed products of alpha- and beta-tetra(L-aspartic acid)s by PAA hydrolase-1 has showed that PAA hydrolase-1 is capable of hydrolyzing only the specific amide bonds between beta-aspartic acid units. The RP-HPLC analysis of the enzymatic hydrolysis of beta-oligo(L-aspartic acid)s (4 and 5 mers) by PAA hydrolase-1 has suggested that the enzymatic hydrolysis of beta-oligo(L-aspartic acid)s occurs via an endo-mode cleavage. In contrast, PAA hydrolase-2 hydrolyzed both alpha- and beta-oligo(L-aspartic acid)s via an exo-mode cleavage to yield L-aspartic acid as a final product. A kinetic study on the enzymatic hydrolysis of alpha-oligo(L-aspartic acid)s (3 to 7 mers) by PAA hydrolase-2 has indicated that Km values are almost independent of the number of monomer units in oligomers of 4 to 7 mers, while that Vmax values are markedly dependent on the chain length and show a maximum value at 5 mer.     

Copper(II)-mediated resolution of alpha-halo carboxylic acids with chiral O,O'-dibenzoyltartaric acid: spontaneous racemization and crystallization-induced dynamic resolution

Herein we present a new example of coordination-mediated resolution of racemic acids by a chiral acid. The reaction of copper(II) acetate monohydrate, optically pure O,O'-dibenzoyltartaric acid (DBTA) and racemic alpha-bromo-2-chlorophenylacetic acid (HL1) in acetonitrile solution afforded a binuclear copper(II) complex with D-DBTA dianion, alpha-bromo-2-chlorophenylacetate and acetate as ligands. After decomposition of the complex with acid, the optically active acid ((R)-HL1) was obtained. Similarly, alpha-bromo-2-fluorophenylacetic acid (HL2), alpha-bromo-2-bromophenylacetic acid (HL3), alpha-chloro-2-chlorophenylacetic acid (HL4), alpha-chloro-2-fluorophenylacetic acid (HL5), alpha-bromophenylacetic acid (HL6), alpha-bromo-4-chlorophenylacetic acid (HL7), 2-bromopropionic acid (HL8) and 2-chloropropionic acid (HL9) were resolved by the same method. Satisfactory results were obtained for HL2 to HL5. For HL6 and HL7, only racemic acids were obtained. For the two alpha-halo aliphatic acids (HL8 and HL9), poor enantioselectivity was obtained. It is more interesting that three acids (HL1, HL2 and HL3) could spontaneously racemize in acetonitrile solution, which resulted in crystallization-induced dynamic resolution (CIDR) with greater than 50% yield.     

Synthesis and spectral studies of copper(II) complexes with amide group ligands

Complexes of copper(II) with 2-(acetylamino)benzoic acid, 2-(benzoylamino) benzoic acid, 2-(aminocarbonyl)benzoic acid, 2-[(phenylamino)carbonyl]benzoic acid, 2-[(1-naphthalenylamino)carbonyl]benzoic acid, 2-[(2-aminophenylamino)carbonyl]benzoic acid, 2-aminobenzanilide, 2(aminobenzoyl)benzoic acid, maleanilic acid and malea-1-naphthalanilic acid have been prepared and characterized by chemical analyses, molar conductivity, magnetic susceptibility measurements, thermal data, IR, electronic and ESR spectra. The visible and ESR spectral studies of these complexes (except those of maleanilic acid and malea-1-naphthalanilic acid) indicate that they are monomeric having either square planar or distorted octahedral geometry around Cu(II). The Cu(II) complexes of maleanilic acid and malea-1-naphthalanilic acid have been tentatively assigned dimeric structures. From the ESR spectra of Cu(II) complexes various parameters have been calculated.     

Photoexchange products of cytosine and 5-methylcytosine with N alpha-acetyl-L-lysine and L-lysine

The photoinduced exchange reactions of cytosine (Ia) and 5-methylcytosine (IIa) with N alpha-acetyl-L-lysine, a derivative of the common amino acid L-lysine, were studied. These reactions of Ia and IIa at pH 7.5 produce, respectively, 2-N-acetylamino-6-(1-cytosinyl)hexanoic acid (Ib) and 2-N-acetylamino-6-(1-(5-methylcytosinyl]hexanoic acid (IIb) as major final products. In addition, small amounts of the corresponding deamination products were formed in the 5-methylcytosine-N alpha-acetyl-L-lysine and cytosine-N alpha-acetyl-L-lysine systems, namely 2-N-acetylamino-6-(1-thyminyl)-hexanoic acid and 2-N-acetylamino-6-(1-uracilyl)hexanoic acid. The compounds Ib and IIb were deacetylated by acid hydrolysis to yield the corresponding lysine products: 2-amino-6-(1-cytosinyl)hexanoic acid (Ic) and 2-amino-6-(1-(5-methylcytosinyl]hexanoic acid (IIc). The compound Ic was identified as a product in the photoreaction of cytosine with L-lysine at near neutral pH, while IIc is found as a product in the corresponding reaction of 5-methylcytosine. The occurrence of the above photoexchange reactions at pH values near those found in physiological systems could have biological implications; in particular, our observations suggest that cytosine and 5-methylcytosine residues, contained in DNA, might react with the epsilon-amino groups of lysine residues in proteins upon UV irradiation of nucleosomes and other DNA-protein complexes under physiological conditions.     

Diels-alder reactions of 3-(2-nitrovinyl)indoles: Formation of carbazoles and bridged carbazoles

The Diels-Alder reactions of 1-substituted-3-(2-nitrovinyl)indoles 3 with quinones and acetylenes give aromatized 1:1 adducts (- nitrous acid) ( 1 ) or (- nitrous acid, -2 hydrogens) 2,5 . Likewise, dimerization (-2 nitrous acids) of 3 gives aromatized 2-(3-indolyl)carbazoles 4 . In contrast, 3 reacts with maleimides 6 to give 1:2 adducts (- nitrous acid or -2 hydrogens) 10 and 11 , respectively, along with smaller amounts of 1:1 adducts (- nitrous acid, -2 hydrogens; or -4 hydrogens) 12 and 13 , respectively. A mechanism for formation of the nitro products 11 and 13 is discussed. A 1:2 adduct (-2 hydrogens) 19 was also obtained from a Diels-Alder reaction between maleimide and the vinylindole produced in situ by condensing 1-methylindole with acetone. The stereochemisty of this 1:2 adduct has been determined by X-ray crystallography.     

Thiophene aldehyde and its derivatives. II

Condensation of thiophene-2-aldehyde with p-aminobenzoic and barbituric acids gives 2-thenylidene -p-aminobenzoic acid and 2-thenyl-idenebarbituric acid. Similarly, 5-nitro-thiophene-2-aldehyde gives 5-nitro-2-thenylidene-p-aminobenzoic acid and 5-nitro-2-thenyl-idenebarbituric acid. Condensation of thiophene-2-aldehyde with nitroethane gives 1-(2-thienyl)-2-nitroprop-1-ene; and 1-nitro-2-(2-thienyl-5-nitro) ethene is synthesized by nitrating thienylnitroethylene.     

Capillary liquid chromatography of chlorophenoxy acid herbicides and their esters in apple juice samples after preconcentration on a cation exchanger based on polydivinylbenzene-N-vinylpyrrolidone

A capillary liquid chromatography (cLC) method with gradient elution has been used to determine chlorophenoxy acid herbicides: 2,4-dichlorophenoxyacetic acid, 4-chloro-2-methylphenoxyacetic acid, 2-(2,4-dichlorophenoxy)propanoic acid, 2-(4-chloro-2-methylphenoxy)propanoic acid, 4-(2,4-dichlorophenoxy)butanoic acid, 4-(4-chloro-2-methylphenoxy)butanoic acid, 2-(2,4,5-trichlorophenoxy)propanoic acid, 2,4-dichlorophenoxyacetic-1-methyl ester and 2,4-dichlorophenoxyacetic-1-butyl ester in spiked apple juice samples with amounts between 0.025 and 0.150 mg kg(-1) of each herbicide. Clean-up and preconcentration of acid and esters were carried out in an Oasis MCX polymer. Detection limits obtained by cLC, between 0.005 and 0.018 mg kg(-1), allowed the determination of chlorophenoxy acids and their esters in apple juice samples around the levels permitted by the European Regulations, with recoveries in the range 84-99% and RSDs between 1 and 4%.     

DiastereoselectiveandEnantioselectiveSynthesisof(1S,2S)-2-Ethyl-1-aminocyclopropaneCarboxylicAcid

During the last decade, 1-aminocyclopropanecarboxylic acid and its derivatives (ACCS) have attracted increasing attention of organic and bioorganic chemists due to their outstanding biological properties, ranging from antimicrobial, insecticidal, plant growth and fruit ripening controls, etc.1. Moreover, the three-membered carbocycle provides building blocks of unprecedented synthetic potential because it undergoes selective ring opening, ring enlargement or cycloaddition reactions2. The mo…     

聚酯酸酐的合成及其药物释放性能研究

将对羟乙氧基苯甲酸分别与已二酰氯、癸二酰氯和对苯二甲酰氯反应,制备了含酯键的二羧酸.经熔融缩聚,合成了主链含酯键的新型聚酯酸酐.通过¹H NMR、IR及元素分析对单体及聚酯酸酐的结构进行了表征.研究了聚酯酸酐的体外降解和药物释放性能,其降解速率和释药速率次序为:聚4,4'-(已二酰氧二乙氧基)双对苯二甲酸＞聚4,4'-(癸二酰氧二乙氧基)双对苯二甲酸＞聚4,4'-(对苯二甲酰氧二乙氧基)双对苯二甲酸.     

Syntheses,Characterization and Stereochemistry of S - and R,S -Hydrogenmalato Dioxotungsten(VI)

Cis -dioxo hydrogenmalato tungstates(VI) j -Na 2 [WO 2 ( S -Hmal) 2 ]·4H 2 O 1 , and Na 2 [WO 2 ( R , S -Hmal) 2 ] 2 (H 3 mal = malic acid) have been prepared from the reactions of excess S- malic acid and R , S -malic acid respectively, with sodium tungstate at ambient temperature. Both complexes were characterized by elemental analyses, conductivity measurement, optical rotation, UV-Vis, IR and NMR spectroscopy. Complex 1 was obtained with predetermined helical chirality at the metal center for a j - cis -configuration, which is established by single crystal X-ray diffraction. The crystal is orthorhombic, space group P 2 1 2 1 2 1 , with unit cell parameters: a = 7.9545(6), b = 10.7440(8), c = 21.045(2)Å, V = 1798.6(2)Å 3 , Z = 4, D c = 2.215 g cm m 3 , F (000) = 1152, R = 0.031, R w = 0.034. Single crystal X-ray diffraction reveals that the cis- dioxo tungstate 1 is octahedrally coordinated by the S -malate through the deprotonated f -hydroxy and f -carboxylate groups, while the g -carboxylic acid groups remain uncomplexed.     

Simple and efficient methods for discrimination of chiral diacids and chiral alpha-methyl amines

The three-component chiral derivatization protocols have been developed for (1)H, (13)C and (19)F NMR spectroscopic discrimination of chiral diacids by their coordination and self-assembly with optically active (R)-α-methylbenzylamine and 2-formylphenylboronic acid or 3-fluoro-2-formylmethylboronic acid. These protocols yield a mixture of diastereomeric imino-boronate esters which are identified by the well-resolved diastereotopic peaks with significant chemical shift differences ranging up to 0.6 and 2.1 ppm in their corresponding (1)H and (19)F NMR spectra, without any racemization or kinetic resolution, thereby enabling the determination of enantiopurity. A protocol has also been developed for discrimination of chiral alpha-methyl amines, using optically pure trans-1,2-cyclohexanedicarboxylic acid in combination with 2-formylphenylboronic acid or 3-fluoro-2-fluoromethylboronic acid. The proposed strategies have been demonstrated on large number of chiral diacids and chiral alpha-methyl amines.     

Continued investigation of the diazotization and coupling spectrophotometric technique for the determination of aromatic amines with 8-amino-1-hydroxynaphthalene-3,6-disulphonic acid and N-(1-naphthyl)ethylenediamine as coupling agents

Twenty more aromatic amines are determined by the diazotization and coupling spectrophotometric technique, with 8-amino-1-hydroxynaphthalene-3,6-disulphonic acid (H-acid) and N-(1-naphthy)ethylenediamine (N-na) as coupling agents. The following are determined by both methods: 2,4-diaminotoluene, 2-aminobenzotrifluoride, 4-benzoxyaniline, 2,4-dimethyl-6-nitroaniline, 4,5-dimethyl-2-nitroaniline, 2-amino-9-fluorenone, naphthionic acid (sodium salt), 3-aminonaphthalene-2, 7-disulphonic acid (monosodium salt), 2-aminonaphthalene-1-sulphonic acid, 4-aminonaphthalene-1-sulphonic acid and 2,4-dibromoaniline. The following are determined only by the N-na method: 5-aminosalicylic acid, 2-amino-4-nitrophenol, 4-amino-2,6-dichlorophenol hydrochloride, 2,5-dimethoxy-aniline, 4-aminothiophenol, 4,4'-diaminodiphenylmethane, 1-naphthylamine, 4,4'-diaminobiphenyl-2,2'-disulphonic acid and 4,4'-diaminostilbine-2,2'-disulphonic acid. The optimum acidities for the different aromatic amines for the N-na method vary considerably. A number of aromatic amines cannot be determined by either method.     

Beilschmiedic Acids F and G,Further Endiandric Acid Derivatives from Beilschmiedia anacardioides

Two new endiandric acid derivatives, beilschmiedic acid F ( 1 ) and beilschmiedic acid G ( 2 ), together with three known constituents, beilschmiedic acid A, beilschmiedic acid C, and sitosterol 3‐β‐D ‐glucopyranoside, were isolated from the stem bark of Beilschmiedia anacardioides. Their structures were elucidated mainly by using a combination of 1D‐ and 2D‐NMR techniques. The structure and relative configuration of beilschmiedic acid G ( 2 ) was also confirmed by X‐ray crystallographic analysis.     

聚唾液酸-透明质酸接枝聚合物的合成及其在药物缓释载体中的应用

聚唾液酸(PSA)经环氧氯丙烷活化后,与透明质酸(HA)在碱性条件下反应合成了系列PSA-HA接枝聚合物(P¹~P⁵, PSA与HA质量比分别为1：1~5 ：1),合成率40%~89%,其结构经FT-IR,元素分析和SEM表征。以胰岛素为模型药物,将P²与胰岛素按2 ：1(m/m)混合时,包封率和载药率分别为85%和38%,平均粒径为3.2 μm。体外释药试验结果表明: P²对胰岛素有一定的体外缓释能力,在6 h内释药89%;在pH 1.2条件下的释药速度大于pH 7.4条件下的释药速度。     

Synthesis and characterization of azo-linked Schiff bases and their nickel(II), copper(II), and zinc(II) complexes

Azo compounds were prepared by coupling of benzenediazonium chloride ions with 1-amino-2-hydroxy-4-naphthalene sulfonic acid under alkaline conditions, and Schiff bases, L_1–3 were then obtained by the condensation of 1-amino-2-hydroxy-3-(phenylazo)-4-naphthalene sulfonic acid, 1-amino-2-hydroxy-3-(4-ethylphenylazo)-4-naphthalene sulfonic acid, and 1-amino-2-hydroxy-3-(4-nitrophenylazo)-4-naphthalene sulfonic acid with salicylaldehyde. New copper(II), nickel(II), and zinc(II) complexes of the Schiff base ligands were also prepared and characterized by spectroscopic methods, magnetic measurements, elemental, and thermogravimetric analysis.     

Ieodoglucomides A and B from a marine-derived bacterium Bacillus licheniformis

Ieodoglucomides A (1) and B (2), unique glycolipopeptides consisting of an amino acid, a new fatty acid, a succinic acid, and a sugar, were isolated from a Marine-derived bacterium Bacillus licheniformis. The absolute stereochemistry of 1 and 2 was determined by deploying coupling constants, Marfey's and Mosher's methods, and literature reviews. Compounds 1 and 2 displayed moderate in vitro antimicrobial activity. Furthermore, ieodoglucomide B (2) exhibited cytotoxic activity against lung cancer and stomach cancer cell lines with GI(50) values of 25.18 and 17.78 μg/mL, respectively.