Microbial metabolism. Part 7 : Curcumin

Microbial metabolism of the cancer chemopreventive agent, curcumin [(1E,6E)-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione] (1) with Pichia anomala (ATCC 20170) yielded four major metabolites, 5-hydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)heptan-3-one (2), 5-hydroxy-7-(4-hydroxy-3-methoxyphenyl)-1-(4-hydroxyphenyl)heptan-3-one (3), 1,7-bis(4-hydroxy-3-methoxyphenyl)heptan-3,5-diol (4), 5-hydroxy-1,7-bis(4-hydroxyphenyl)heptane-3-one (5) and two minor products, 1-(4-hydroxy-3-methoxyphenyl)-7-(4-hydroxyphenyl)heptane-3,5-diol (6) and 1,7-bis(4-hydroxyphenyl)heptane-3,5-diol (7). The structures of compounds 2-5 were established on the basis of spectroscopic data. Compounds 6 and 7 were assigned tentative structures.     

Three new diarylheptanoids and their antioxidant property

Three new diarylheptanoids,i.e.,sodium(5S,2E)-1,7-bis(4-hydroxyphenyl)-1-hydroxy-2-hepten-5-sulfonate(1), sodium(5R,2E)-1,7-bis(4-hydroxyphenyl)-1-hydroxy-2-hepten-5-sulfonate (2) and 3,5-diacetoxy-1-(3-methoxy-4,5-dihydroxy- phenyl)-7-(4-hydroxy-3-methoxyphenyl)heptane (3) were isolated from the rhizomes of Zingiber officinale.The structures of the new compounds were elucidated on the basis of spectroscopic methods.The antioxidant activities of 3 were assayed by in vitro models involving DPPH free radicals and superoxide anion radicals.     

Three-coordinate organoboron compounds BAr2R (Ar = mesityl, R = 7-azaindolyl- or 2,2'-dipyridylamino-functionalized aryl or thienyl) for electroluminescent devices and supramolecular assembly

Eight novel three-coordinate boron compounds with the general formula BAr(2)L, in which Ar is mesityl and L is a 7-azaindolyl- or a 2,2'-dipyridylamino-functionalized aryl or thienyl ligand, have been synthesized by Suzuki coupling, Ullmann condensation methods, or simple substitution reactions (L = p-(2,2'-dipyridylamino)phenyl, 1; p-(2,2'-dipyridylamino)biphenyl, 2; p-(7-azaindolyl)phenyl, 3; p-(7-azaindolyl)biphenyl, 4; 3,5-bis(2,2'-dipyridylamino)phenyl, 5; 3,5-bis(7-azaindolyl)phenyl, 6; p-[3,5-bis(2,2'-dipyridylamino)phenyl]phenyl, 7; 5-[p-(2,2'-dipyridylamino)phenyl]-2-thienyl, 8). The structures of 1, 3, and 5-7 have been determined by X-ray diffraction analyses. These new boron compounds are bright blue emitters. Electroluminescent devices using compound 2 or 8 as the emitter and the electron-transport layer have been successfully fabricated. Molecular orbital calculations (Gaussian 98) have established that the blue emission of compounds 1-8 originates from charge transfer between the pi orbital of the ligand L and the p(pi) orbital of the boron center. The ability of these boron compounds to bind to metal centers to form supramolecular assemblies was demonstrated by treatment of compound 2 with Zn(O(2)CCF(3))(2), which generated a 1:1 chelate complex [2.Zn(O(2)CCF(3))(2)] (10), and also by treatment of compound 4 with AgNO(3), yielding a 2:1 coordination compound [(4)(2).Ag(NO(3))] (11). In the solid state, compounds 10 and 11 form interesting head-to-head and tail-to-tail extended structures that host solvent molecules such as benzene.     

ortho-Directed electrophilic boronation of a benzyl ketone: the preparation, X-ray crystal structure, and some reactions of 4-ethyl-1-hydroxy-3-(4-hydroxyphenyl)-2-oxa-1-boranaphthalene

4-Ethyl-1-hydroxy-3-(4-hydroxyphenyl)-2-oxa-1-boranaphthalene (4) is formed in 78% yield from the reaction of 1-(4-methoxyphenyl)-2-phenylbutan-1-one with an of excess boron tribromide in dichloromethane followed by treatment with water. Reaction of 4 with iodine in aqueous sodium hydroxide gives a second oxaboracycle, 3-ethyl-1-hydroxy-3-(4-hydroxybenzoyl)-2,1-benzoxaborolane (5). The X-ray crystal structure determinations of both boron heterocycles are reported. Other new compounds reported are 1-(4-hydroxyphenyl)-2-(1-hydroxyphenyl)-butan-1-one (6), formed by reaction of 4 with alkaline hydrogen peroxide, and 1-(4-hydroxyphenyl)-2-(2-biphenyl)-butan-1-one (8), formed by coupling of 4 with bromobenzene in the presence of Pd(PPh₃) ₄.     

一种半受阻酚类抗氧剂中间体的合成及抗氧化性能研究

采用2-甲基-6-叔丁基苯酚和丙烯酸甲酯为原料,通过迈克尔加成反应合成半受阻酚类抗氧剂中间体β-(3-甲基-5-叔丁基-4-羟基苯基)丙酸甲酯.条件优化实验确定该抗氧剂中间体的最佳合成工艺条件为:2-甲基-6-叔丁基苯酚与丙烯酸甲酯物质的量之比为1∶1.1,催化剂KOH与2-甲基-6-叔丁基苯酚的物质的量比为1∶10,丙烯酸甲酯滴加温度为90℃,丙烯酸甲酯滴加时间为30 min,反应温度为130℃,反应时间为5 h.在此条件下,半受阻酚类抗氧剂中间体β-(3-甲基-5-叔丁基-4-羟基苯基)丙酸甲酯的收率大于70%,熔程41.6℃~44.0℃.IR和1H NMR证实所合成目标产物的化学结构与其理论结构相一致.DPPH法测定半受阻酚类抗氧剂中间体清除自由基的性能,并与全受阻酚类抗氧剂中间体β-(3,5-二叔丁基-4-羟基苯基)丙酸甲酯进行对比.结果表明,由于邻位取代基的不对称效应,使得空间位阻较小的不对称抗氧剂中间体β-(3-甲基-5-叔丁基-4-羟基苯基)丙酸甲酯清除DPPH·的活性高于邻位取代基空间位阻较大的对称抗氧剂中间体清除DPPH·的活性.     

Three-coordinate organoboron with a B=N bond: substituent effects, luminescence/electroluminescence and reactions with fluoride

Five new three-coordinate boron compounds with a B=N bond involving an indole or a substituted indole ligand including B(mesityl)2(indolyl), (1), B(mesityl)2(2-Me-indolyl), (2), B(mesityl)2(3-Me-indolyl), (3), B(mesityl)2 (7-Me-indolyl), (4), and B(mesityl)2(3-Ph-indolyl), (5) have been synthesized. The structures of these new compounds were determined by X-ray diffraction analyses. All five compounds are luminescent involving a charge transfer transition between the indolyl pi orbital and the boron p(pi) orbital. The substituent group on the indolyl ring was found to have a subtle impact on the electronic properties of compounds. NMR experiments established that the methyl group at the 7-position of indole is most effective in blocking the rotation of the mesityl group around the B-C bond. The addition of fluoride ions to this group of compounds causes luminescent quenching and an irreversible decomposition of the compounds due to the reaction of the F- adduct with water molecules. The potential use of this group of compounds as blue emitters in electroluminescent (EL) devices was demonstrated by the successful fabrication of a four-layer EL device where 1 was used as the emitter. The EL device displays a blue emission with a maximum luminescence being 1037 cd m(-2) and a maximum current efficiency about 0.7 cd A(-1) at 5 V.     

The Preparation of Dicompartmental Multifunctional Group Ligands

A convenient method for the preparation of the phenol-based ligands 1,6-bis(2-thiophenyl)-2,5-bis(2-hydroxy-3-hydroxymethyl-5-methylbenzyl)-2,5-diazahexane and 1,6-bis(5-methyl-2-thiophenyl)-2,5-bis(2-hydroxy-3-hydroxymethyl-5-methyl-benzyl)-2,5-diazahexane possessing two dissimilar compartments having multifunctional groups is reported. To synthesize these ligands, an equivalent of 1,6-bis(2-thiophene)-2,5-diazahexane or 1,6-bis(5-methyl-2-thiophene)-2,5-diazahexane and two equivalents of 2,2-dimethyl-6-methyl-8-(chloromethyl)benzo-1,3-dioxin were reacted in the presence of Na₂CO₃ in 1,4-dioxane, followed by acid hydrolysis of an acetonide-protecting group. Characterization data for the new compounds is reported.     

pH-metric studies on formation constants of the complexes of substituted pyrazoles with some lanthanide metal ions and the influence of ionic strengths on complex equilibria in a 70% dioxane-water mixture

The pK a values of N-heterocyclic compounds (substituted pyrazoles) in a 70% (v/v) dioxane-water mixture have been determined using pH-metric measurements. The stability constants of the complexes of Dy(III), Nd(III), Sm(III), and Tb(III) with 3-(2-hydroxyphenyl)-5-methylpyrazole, l-phenyl-3-(2-hydimyphenyl)-5-methylpyrazole 3-(2-hydroxy-4-methylphenyl)-5-methylpyrazole, and l-phenyl-3-(2-hydroxy-4-methylphenyl)-5-methylpyrazole have been determined by the pH-metric method at ( 300 ± 0.1) K. The effect of ionic strengths on the complexes of Sm³⁺ and Pr³⁺ ions with pyrazole has been investigated in the internal from 0.02 to 0.1 mol dm⁻³ (sodium perchlorate) in the pH range 2–3.     

Efficient single-layer electroluminescent device based on a bipolar emitting boron-containing material

A novel multifunctional 1,6-bis(2-hydroxyphenyl)pyridine boron bis(4-n-butyl-phenyl)phenyleneamine compound in which the hole-transporting (HT), electron-transporting (ET), and emitting (EM) components are integrated into a single molecule was synthesized and used as an emitting material to fabricate an efficient single-layer electroluminescent device.     

One new and several minor diarylheptanoids from Amomum muricarpum

A new natural diarylheptanoid, designated muricarpin, together with four diarylheptanoids were isolated from the rhizomes of Amomum muricarpum Elmer (Zingiberaceae) growing in Vietnam. Three known compounds, 1,7-bis(3,4-dihydroxyphenyl)heptan-3-yl acetate, 1-(4'-hydroxyphenyl)-7- (3″,4″-dihydroxyphenyl)heptan-3-yl acetate and 1-(3',4'-dihydroxyphenyl)-7-(4″-hydroxyphenyl)-heptan-3-one were isolated for the first time from the genus Amomum, meanwhile (5R)-5-hydroxy-1,7-bis(4-hydroxyphenyl)-heptan-3-one was found for the first time in plants. Their structures were determined using spectroscopic analyses.     

Process development and large-scale synthesis of NK1 antagonist

A scaleable synthetic route is described to obtain 2-(4-acetylpiperadin-1-yl)-6-[3,5-bis(trifluoromethyl)phenylmethyl]-4-(2-methylphenyl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,5]oxazocin-5-one (1, KRP-103) as a neurokinin (NK)(1) antagonist. The key step in the synthesis is the intramolecular cyclization of N-[3,5-bis(trifluoromethyl)phenylmethyl]-N-(3-hydroxypropyl)-4-chloro-6-(2-methylphenyl)-2-methylthiopyrimidine-5-carboxamide (15) which was obtained by amide formation between 4-(2-methylphenyl)-2-methylthio-6-oxo-1,6-dihydropyrimidine-5-carboxylic acid (8) and 3-[3,5-bis(trifluoromethyl)phenylmethylamino]-1-propanol (3). Treatment of 15 with 1,8-diazabicyclo[5,4,0]undec-7-ene provided 6-[3,5-bis(trifluoromethyl)phenylmethyl]-4-(2-methylphenyl)-2-methylthio-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,5]oxazocin-5-one (6). This intermediate (6) is transformed into the candidate compound (1) by two steps; oxidation, and substitution reaction of the resultant sulfone (7) with 1-acetylpiperazine. This synthetic method is free of chromatographic purification and is amenable to large scale synthesis.     

New glucose esters from the fresh leaves of Jacaranda mimosaefolia

From the fresh leaves of Jacaranda mimosaefolia were isolated Phytoquinoids 1-4 established as beta-D-glucopyranose 2-benzeneacetatel,6-bis(1-hydroxy-4-oxo-2,5-cyclohexadiene-1-acetate), for which the name Jacaranoside is proposed; beta-D-glucopyranose 2-(4-hydroxybenzeneacetate) 1,6-bis(1-hydroxy-4-oxo-2,5-cyclohexadiene-1-acetate), for which the name Jacarandol is proposed; beta-D-glucopyranose 2-benzeneacetate 1-(1-hydroxy-4-oxo-2,5-cyclohexadiene-1-acetate) and beta-D-glucopyranose 1,6-bis (1-hydroxy-4-oxo-2,5-cyclohexadiene-1-acetate) respectively.     

Reaction of 1,3,4,6-tetraketones with <Emphasis Type="Italic">p</Emphasis>-toluidine and benzaldehyde

Reactions of 1,6-diphenylhexane-1,3,4,6-tetraone, octane-2,4,5,7-tetra-one, and decane-3,5,6,8-tetraone with a mixture of p-toluidine and benzaldehyde afforded, respectively, 2-[4-benzoyl-3-hydroxy-1-(4-methylphenyl)-5-phenyl-1H-pyrrol-2-yl]-1-phenylethanone, (1E)-1-[4-acetyl-3-hydroxy-1-(4-methylphenyl)-5-phenyl-1,5-dihydro-2H-pyrrol-2-ylidene]propan-2-one, and 2-hydroxy-1-(4-methylphenyl)-2-(2-oxobutyl)-4-propanoyl-5-phenyl-1,2-dihydro-3H-pyrrol-3-one.     

Synthesis,characterization, and antitumour studies of some curcuminoid analogues and their aluminum complexes

Aluminum(III) complexes of three curcuminoid analogues [1,7-diphenyl-1,6-heptadiene-3,5-dione, HL¹; 1,7-bis(2-hydroxyphenyl)-1,6-heptadiene-3,5-dione, HL²; and 1,7-bis(4-ethoxyphenyl)-1,6-heptadiene-3,5-dione, HL³] of [AlL₃] stoichiometry were synthesized and characterized by UV, IR, ¹H NMR, and mass spectral data. The compounds were investigated for cytotoxic and antitumor activities. The aluminum chelates are remarkably active compared to free curcuminoid analogues. The aluminum complex of HL² with hydroxyl in the phenyl ring was most active towards Ehrlich ascites carcinoma cells (concentration needed for 50% inhibition of 5?μg/mL) and cultured L929 cells (1?μg/mL produced 60?+?3% cell death). Increase in lifespan and reduction of solid tumor volume in mice were also largest for the aluminum complex of HL². The study reveals that the antitumor activities of curcuminoids are more enhanced by complexation with aluminum than with transition metal ions.     

Synthesis of <Emphasis Type="Italic">N</Emphasis>-β-haloethyl derivatives of bis(oxytriazene oxides) bearing the NCH<Subscript>2</Subscript>O fragment

Synthetic procedures towards 3-monosubstituted functional derivatives of 1-alkoxy-1-triazene 2-oxides were elaborated. Alkylation of the synthesized compounds with chloromethoxy derivatives of 3,3-bis(2-haloethyl)-1-hydroxy-1-triazene 2-oxides gave (2-chloro/ bromoethyl) derivatives of 1,2,3,6,7,8-hexaaza-5-oxa-3-alkoxyocta-1,6-diene 2,7-dioxides. 2-Iodoethyl-1,2,3,6,7,8-hexaaza-5-oxa-3-alkoxyocta-1,6-diene 2,7-dioxides were first synthesized by the reaction of the corresponding bromoethyl derivatives with NaI.     

Theoretical study on photophysical properties of phenolpyridyl boron complexes

Organoboron complexes have potential application in organic light-emitting devices (OLEDs). Our group has synthesized four phenolpyridyl boron complexes (Inorg. Chem. 2006, 45, 2788), which can function as an electron transport materials (ETM), white and blue emitters, and exhibit high efficiency and stability. To reveal the relationship between the properties and structures of these functional materials, theoretical analysis of spectral properties and electronic structures of these complexes was systematically characterized with the B3LYP and 6-31G* basis set. The calculated absorption and emission spectra of these systems are in good agreement with the experimental ones. It is clear seen that these transitions are charge transferred along 2,6-bis(2-hydroxyphenyl)pyridyl boron moiety, and the contribution of boron atom in these compounds to the main transition orbitals is vanishingly small. The substitution of methyl and methoxyl for hydrogen does not change the absorption wavelengths and transition natures, but influences the radioactive efficiencies and electron transport properties, which are observed and discussed in detail. Furthermore, large red shifts of fluorescence are caused by replacing the hydrogen with CN or NO2 groups, which indicates that they are potential candidates as green-light-emitting materials. These results are favorable to further understanding the photophysical properties of this kind of complexes.     

Phenolic glycosides from Pyrola japonica

Five new phenolic glycosides, 2-beta-D-glucopyranosyloxy-5-hydroxyphenylacetic acid methyl ester (4), 4-hydroxy-2-[3-hydroxy-3-methylbutyl]-5-methylphenyl beta-D-glucopyranoside (5), 4-hydroxy-2-[(E)-4-hydroxy-3-methyl-2-butenyl]-5-methylphenyl beta-D-glucopyranoside (7), 4-hydroxy-2-[(2E,6Z)-8-beta-D-glucopyranosyloxy-3,7-dimethylocta-2,6-dien-1-yl]-5-methylphenyl beta-D-glucopyranoside (8), and 2,7-dimethyl-1,4-dihydronaphthalene-5,8-diol 5-O-beta-D-xylopyranosyl(1-->6)-beta-D-glucopyranoside (10), were isolated from the whole plants of Pyrola japonica (Pyrolaceae), together with androsin, (-)-syringaresinol glucoside, homoarbutin, pirolatin, hyperin, monotropein and chimaphilin.     

4个天然1,7-二芳基庚烷类化合物的合成

合成了4个天然1,7-二芳基庚烷类化合物:1-(4′-羟基-3′-甲氧基苯基)-7-(4″-羟基苯基)-5-羟基-3-庚酮(1),1-(4′-羟基-3′-甲氧基苯基)-7-(4″-羟基苯基)-4-庚烯-3-酮(2),1-(3′,4′-二羟基苯基)-7-(4″-羟基苯基)-5-羟基-3-庚酮(3),1-(3′,4′-二羟基苯基)-7-(4″-羟基苯基)-4-庚烯-3-酮(4).化合物1,2,4为首次合成.     

Mononuclear Schiff base boron halides: synthesis, characterization, and dealkylation of trimethyl phosphate

A series of mononuclear boron halides of the type LBX(2) [LH = N-phenyl-3,5-di-tert-butylsalicylaldimine, X = Cl (2), Br (3)] and LBX [LH2 = N-(2-hydroxyphenyl)-3,5-di-tert-butylsalicylaldimine, X = Cl (7), Br (8); LH2 = N-(2-hydroxyethyl)-3,5-di-tert-butylsalicylaldimine, X = Cl (9), Br (10); and LH2 = N-(3-hydroxypropyl)-3,5-di-tert-butylsalicylaldimine, X = Cl (11), Br (12)] were synthesized from their borate precursors LB(OMe)2 (1) (LH = N-phenyl-3,5-di-tert-butylsalicylaldimine) and LB(OMe) [LH2 = N-(2-hydroxyphenyl)-3,5-di-tert-butylsalicylaldimine (4), N-(2-hydroxyethyl)-3,5-di-tert-butylsalicylaldimine (5), N-(3-hydroxypropyl)-3,5-di-tert-butylsalicylaldimine (6)]. The boron halide compounds were air and moisture sensitive, and upon hydrolysis, compound 7 resulted in the oxo-bridged compound 13 that contained two seven-membered boron heterocycles. The boron halide compounds dealkylated trimethyl phosphate in stoichiometric reactions to produce methyl halide and unidentified phosphate materials. Compounds 8 and 12 were found to be the most effective dealkylating agents. On reaction with tert-butyl diphenyl phosphinate, compound 8 produced a unique boron phosphinate compound LB(O)OPPh2 (14) containing a terminal phosphinate group. Compounds 1-14 were characterized by 1H, 13C, 11B, 31P NMR, IR, MS, EA, and MP. Compounds 5, 6, and 11-14 also were characterized by single-crystal X-ray diffraction.     

Synthesis of 2-hydroxy-2-phenylethylamino derivatives as potential α-adrenergic blocking agents

The synthesis of N,N'-bis[6-(2-hydroxy-2-phenylethylamino)hexyl] cystamines 4 , and N-(2-hydroxy-2-phenylethyl)-1,6-hexanediamines 6 are described. Compounds 4 were obtained by condensation of the requisite epoxide 2 with 3-(6-aminohexyl)-1,3-thiazolidine followed by dimerization with opening of the thiazolidine ring. A similar method was used for the preparation of compounds 6. In order to prepare 4j (N,N'-bis{6-[2-hydroxy-2(3,4-dihydroxyphenyl)ethylamino]hexyl}cystamine), several procedures were tested; the method of choice involved the use of 3,4-dihydroxybenzaldehyde with both hydroxy groups protected as methoxymethyl ethers.