海洋真菌Nigrospora sphaerica的化学成分(Ⅱ)

目的对海洋真菌Nigrospora sphaerica中的化学成分进行研究。方法采用硅胶柱色谱、凝胶以及HPLC等方法进行分离纯化,根据理化性质和光谱数据进行结构鉴定。结果分离得到了8个化合物,分别鉴定为柄曲霉素(sterigmatocystin,1)、4-苄基-3-苯基-5氢呋喃酮(4-benzyl-3-phenyl-5H-furan-2-one,2)、异黄光素[7,8-dimethyl,benzo(g)pteridine-2,4(1H,3H)-dione,3]、5,8二羟基-7甲氧基黄酮(5,8-dihydroxy-7-methoxy-2-phenyl,4H-1-benzopyran-4-one,4)、1(2H)-3,4-二氢-4,8二羟基萘[3,4-dihydro-4,8-dihydroxy,1(2H)-naphthalenone,5]、3,5双去氧-5-苯基戊糖酸γ内酯(3,5-dideoxy-5-phenyl-,γ-lactone,pentonic acid,6)、4-羟基苯乙醇乙酯(4-hydroxyphe-nylethyl acetate,7)、1,4-二氧-2,5-二酮-3,6-二苯甲基聚酯[3,6-bis(phenylmethyl)-1,4-dioxane-2,5-dione,8]。结论真菌Nigrospora sphaerica为首次从海洋中分离得到,化合物1-8为首次从该菌中分离得到。     

A new alkaloid from Dysoxylum binectariferum

Two compounds (1 and 2) have been isolated from the stem bark of Dysoxylum binectariferum (Roxb.) Hook. f. ex Bedd. Compound 1 is rohitukine [5,7-dihydroxy-2-methyl-8-[4-(3-hydroxy-1- methyl)-piperidinyl]-4H-1-benzopyran-4-one], a known compound that has anti-inflammatory and immunomodulatory activities. Compound 2 is a new alkaloid, named rohitukine N-oxide, the structure of which was elucidated on the basis of spectral evidences and comparison with the 1H NMR data of rohitukine.     

Synthesis and antioxidant evaluation of some new 3-substituted coumarins

3-Acetylcoumarin (1) was utilized as a key intermediate for the synthesis of 2-aminothiazole derivative 3 via bromination of 1 to afford acetylbromide 2 followed by treatment with thiourea or via Biginelli reaction of 1. Treatment of 3 with 5-chloro-3-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde, 2-methyl-4H-benzo[d][1,3]oxazin-4-one, furo[3,4-b]pyrazine-5,7-dione or 2-methyl-5,6,7,8-tetrahydro-4H-benzothieno[2,3-d][1,3]oxazin-4-one afforded diazine derivatives 4-7. Also, pyridopyrimidine 8 was obtained via a one pot reaction of 6-aminothiouracil, p-chlorobenzaldehyde and 3-acetylcoumarin. Moreover, refluxing of 6-aminothiouracil with one equivalent amount of 2 afforded the thiazolopyrimidine 9, while the pyrrolothiazolopyrimidine 10 was revealed when two equivalent amounts of 2 was used. Furthermore, treatment of enamine 11 with 2-aminobenzothiazole or 6-aminothiouracil afforded the pyrimidine derivatives 12 and 13, respectively. Transamination of enamine 11 with m-anisidine followed by cyclization of the resulting enaminone 14 gave the desired quinoline 15. Also, treatment of 11 with thiophenol in dioxane gave the mercapto derivative 16. Moreover, coupling of 11 with 4,6-dimethyl-1H-pyrazolo[3,4-b]pyridin-3-yl-diazonium chloride, followed by complete cyclization of the resulting product afforded the pyridopyrazolothiazine 19 via the intermediate 18. Furthermore, the pyrazolopyrimidine 20 was revealed via a one pot condensation of 11, 3-methyl-1-phenyl-1H-pyrazol-5(4H)-one and ammonium acetate. The thiadiazine derivatives 21-23 were obtained via treatment of 2 with the corresponding o-aminothiols. Desulphonation of 23 afforded the pyrazolotriazine 24. Finally, reaction of 2 with 2-hydroxybenzaldehyde gave benzofuran derivative 25. Representative compounds of the synthesized products were evaluated as antioxidant agents.     

Studies in the synthesis of furocoumarins. Part 29: Synthesis of aminomethyl psoralen and angelicin derivatives as potential photo-chemotherapeutic agents.

Bromination of 2,7-dimethylfuro[2,3-h]benzopyran-5[H]-one (1a) and 2,5-dimethylfuro[3,2-g]benzopyran-7[H]-one (2a) with N-bromosuccinimide gave 2-bromomethyl-7-methylfuro[2,3-h]benzopyran-5[H]-one (1b) and 2-bromomethyl-5-methylfuro[3,2-g]benzopyran-7[H]-one (2b), respectively. The derivatives 1b and 2b were converted to 2-aminomethyl derivatives 1 c-h and 2 c-f by treatment with the appropriate secondary amine. The structures of 2-bromomethyl derivatives 1b and 2b have been confirmed by 13C-NMR spectra.     

5-HT and benzodiazepine receptor ligands. III. Synthesis and receptor affinities of 1,2,4-triazolo[4',3':1,6]pyridazino[4,5-b]quinoline and 2,3-dihydro-9-phenyl-1H-pyrrolo[3,4-b]quinoline-1-one derivatives

The syntheses as well as 5-HT and Benzodiazepine receptor binding studies of some 1,2,4-Triazolo[4',3':1,6]piridazino[4,5-b]quinoline and 2,3-Dihydro-9-phenyl-1H-pyrrolo[3,4-b]quinoline-1-one derivatives are reported. While the triazole-containing heterocycles are devoid of any biological activity, 2-benzyl-2,3-dihydro-9-phenyl-1H-pyrrolo[3,4-b]quinoline-1-one shows some affinity for the central type of benzodiazepine receptors.     

Synthesis of new N,N-disubstituted 4-amino-5,6-dihydro-3-phenyl-2H-thieno[2,3-h]-1-benzopyran-2-ones

The synthesis of some N,N-disubstituted 4-amino-5,6-dihydro-3-phenyl-2H-thieno[2,3-h]-1-benzopyran-2-ones (4a-f), by reaction of phenylchloroketene with a series of N,N-disubstituted (E)-5-aminomethylene-6,7-dihydrobenzo[b]thiophen-4(5)-ones, followed by dehydrochlorination in situ of the primary adducts with DBN, is described. A moderate local anaesthetic activity was observed in the title compounds, particularly in 4e.     

Characterization of 1,2,3,4-diepoxybutane-2'-deoxyguanosine cross-linking products formed at physiological and nonphysiological conditions

1,2,3,4-Diepoxybutane (DEB), an in vivo metabolite of 1,3-butadiene (BD), is a carcinogen and mutagen. The strong carcinogenicity/mutagenicity of DEB has been attributed to its high DNA reactivity and cross-linking ability. Recently, we have demonstrated that under in vitro physiological conditions (pH 7.4, 37 degrees C), the reaction of DEB with 2'-deoxyguanosine (dG) produced two diastereomeric pairs of the major nucleoside adducts resulting from alkylation at the N1- and N7-positions of dG, that is, 2'-deoxy-1-(2-hydroxy-2-oxiranylethyl)guanosine and 2'-deoxy-7-(2-hydroxy-2-oxiranylethyl)guanosine, respectively [Zhang, X.-Y., and Elfarra, A. A. (2005) Chem. Res. Toxicol. 18, 1316]. As each of these adducts contains an oxirane ring, the abilities of these adducts to form cross-linking products with dG under physiological conditions were investigated. Incubation of the N7 nucleoside adducts and their corresponding guanine product with dG led to formation of 7,7'-(2,3-dihydroxy-1,4-butanediyl)bis[2-amino-1,7-dihydro-6H-purin-6-one] (bis-N7G-BD), a known DEB cross-linking product. Incubation of the N1 nucleoside adducts with dG led to formation of a pair of diastereomers of 2'-deoxy-1-[4-(2-amino-1,7-dihydro-6H-purin-6-on-7-yl)-2,3-dihydroxybutyl]-guanosine (N7G-N1dG-BD), which are novel cross-linking products. Interestingly, the reaction of DEB with dG in glacial acetic acid at 60 degrees C yielded different cross-linking products, which were characterized as 2-amino-9-hydroxymethyl-4-{4-[2-amino-9- or 7-(4-acetyloxy-2,3-dihydroxybutyl)-1,7-dihydro-6H-purin-6-on-7- or 9-yl]-2,3-dihydroxybutyl}-8,9-dihydro-7H-[1,4]oxazepino[4,3,2-gh]purin-8-ol (PA2) and 9,9'-bis(4-acetyloxy-2,3-dihydroxybutyl)-7,7'-(2,3-dihydroxy-1,4-butanediyl)bis[2-amino-1,7-dihydro-6H-purin-6-one] (PA4). Collectively, these results increase our understanding of the chemical reactivity and cross-linking ability of DEB under both physiological and nonphysiological conditions.     

The role of the 5-HT1D receptor as a presynaptic autoreceptor in the guinea pig

The present study investigated the role of the 5-hydroxytryptamine (5-HT, serotonin)1D receptor as a presynaptic autoreceptor in the guinea pig. In keeping with the literature, the 5-HT1B selective antagonist, 1'-methyl-5-[[2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]carbonyl]-2,3,6,7-tetrahydrospiro [furo[2,3-f]indole-3,4'-piperidine]oxalate (SB224289) potentiated [3H]5-HT outflow from pre-labelled slices of guinea pig cerebral cortex confirming its role as a presynaptic autoreceptor in this species. In addition, the 5-HT1D receptor-preferring antagonists, 1-[2-[4-(6-fluoro-1H-indol-3-yl)-3,6-dihydro-2H-pyridin-1-yl]-ethyl]-3-pyridin-4-yl-methyl-tetrahydro-pyrimidin-2-one (LY367642), (R)-1-[2-(4-(6-fluoro-1H-indol-3-yl-)-3,6-dihydro-1(2H)-pyridinyl)ethyl]-3,4-dihydro-1H-2-benzopyran-6-carboxamide (LY456219), (S)-1-[2-(4-(6-fluoro-1H-indol-3-yl-)-3,6-dihydro-1(2H)-pyridinyl)ethyl]-3,4-dihydro-1H-2-benzopyran-6-carboxamide (LY456220) and 1-[2-[4-(4-fluoro-benzoyl)-piperidin-1-yl]-ethyl]-3,3-dimethyl-1,2-dihydro-indol-2-one (LY310762), potentiated [3H]5-HT outflow from this preparation with potencies (EC50 values=31-140 nM) in the same range as their affinities for the guinea pig 5-HT1D receptor (Ki values=100-333 nM). The selective 5-HT1D receptor agonist, R-2-(4-fluoro-phenyl)-2-[1-[3-(5-[1,2,4]triazol-4-yl-1H-indol-3-yl)-propyl]-piperidin-4-ylamino]-ethanol dioxylate (L-772,405), inhibited [3H]5-HT outflow. In microdialysis studies, administration of either SB224289 or LY310762 at 10 mg/kg by the intraperitoneal (i.p.) route, potentiated the increase in extracellular 5-HT concentration produced by a maximally effective dose of the selective serotonin re-uptake inhibitor, fluoxetine (at 20 mg/kg i.p.). In addition, the 5-HT1D receptor-preferring antagonist and 5-HT transporter inhibitor, LY367642 (at 10 mg/kg i.p.), elevated extracellular 5-HT concentrations to a greater extent than a maximally effective dose of fluoxetine. It is concluded that the 5-HT1D receptor, like the 5-HT1B receptor, may be a presynaptic autoreceptor in the guinea pig.     

Characterization of the reaction products of 2'-deoxyguanosine and 1,2,3,4-diepoxybutane after acid hydrolysis: formation of novel guanine and pyrimidine adducts

1,2,3,4-diepoxybutane (DEB), an important in vivo metabolite of 1,3-butadiene (BD), is a potent mutagen and a known carcinogen. Recently, DEB has been shown to react with 2'-deoxyguanosine (dG) at 37 degrees C and pH 7.4 to yield a series of nucleoside adducts, resulting from alkylation at the 7-, 1-, and N(2)-positions of dG. In addition, adducts with fused ring systems are formed. In the present study, new adducts are characterized after DEB was allowed to react with dG at pH 7.4 and the reaction mixture was then subjected to acid hydrolysis. These adducts are 7-hydroxy-6-hydroxymethyl-5,6,7,8-tetrahydropyrimido[1,2-a]purin-10(1H)one (H2), 2-amino-1-(4-chloro-2,3-dihydroxybutyl)-1,7-dihydro-6H-purin-6-one (H4), 2-amino-1-(2,3,4-trihydroxybutyl)-1,7-dihydro-6H-purin-6-one (H1'/H5'), 7,8-dihydroxy-1,5,6,7,8,9-hexahydro-1,3-diazepino[1,2-a]purin-11(11H)one (H2'), and 5-(3,4-dihydroxy-1-pyrrolidinyl)-2,6-diamino-4(3H)pyrimidinone (H3'). The previously characterized guanine adducts, 2-amino-7-(3-chloro-2,4-dihydroxybutyl)-1,7-dihydro-6H-purin-6-one (H3) and 2-amino-7-(2,3,4-trihydroxybutyl)-1,7-dihydro-6H-purin-6-one (H4'), were also detected. Acid hydrolysis of purified dG-DEB adducts confirmed that H2, H3/H4', H2', and H4/H1'/H5' are the hydrolysis products of N-(2-hydroxy-1-oxiranylethyl)-2'-deoxyguanosine (P4-1 and P4-2), 6-oxo-2-amino-9-(2-deoxy-beta-d-erythro-pentofuranosyl)-7-(2-hydroxy-2-oxiranylethyl)-6,9-dihydro-1H-purinium ion (P5 and P5'), 7,8-dihydroxy-3-(2-deoxy-beta-d-erythro-pentofuranosyl)-3,5,6,7,8,9-hexahydro-1,3-diazepino[1,2-a]purin-11(11H)one (P6), and 1-(2-hydroxy-2-oxiranylethyl)-2'-deoxyguanosine (P8 and P9), respectively. On the other hand, the novel pyrimidine adduct H3' is formed by the decomposition of P5 and P5' during the incubation and hydrolysis. These results may facilitate the development of useful biomarkers of exposure to DEB and its precursor BD.     

High-affinity, non-peptide agonists for the ORL1 (orphanin FQ/nociceptin) receptor

The discovery of 8-(5,8-dichloro-1,2,3,4-tetrahydro-naphthalen-2-yl)-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one, 1a, as a high-affinity ligand for the human ORL1 (orphanin FQ/nociceptin) receptor led to the synthesis of a series of optimized ligands. These compounds exhibit high affinity for the human ORL1 receptor, exhibit moderate to good selectivity versus opioid receptors, and behave as full agonists in biochemical assays. In this paper we present the synthesis, structure-activity relationship (SAR), and biochemical characterization of substituted 1-phenyl-1,3,8-triazaspiro[4.5]decan-4-ones culminating in the discovery of 8-(5-methyl-1,2,3,4-tetrahydro-naphthalen-1-yl)-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one, 1p, and 8-acenaphten-1-yl-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one 1q, two high-affinity, potent ORL1 receptor agonists with good to moderate selectivity versus the other opioid receptors.     

Synthesis, spectroscopy and alkylating properties of Pd(II) complexes of phosphorohydrazones of coumarin and chromone with potential antibacterial activity

Novel palladium(II) complexes (4-6) have been synthesized from the reaction of (E)-3{[(diethoxythiophosphoryl)-methylhydrazone]-methylene}-4-hydroxy-2H-1-benzopyran-2-one (1), E)-3-{[(dimethoxythiophosphoryl)-methylhydrazine]-methylidene}-3,4-dihydro-2H-1- benzopyran-2,4-dione (2) and (E)-3-{[(diethoxythiophosphoryl)-hydrazone]-methylene}- 4H-1-benzopyran-4-one (3), respectively, with PdCl2(PhCN)2. These complexes have been characterized by elemental analysis and spectroscopic studies. The alkylating activity of the complexes was examined in vitro toward 4-(4'-nitrobenzyl)pyridine (NBP test). The palladium(lI) complexes were found to possess alkylating activity. The compounds (4-6) have been screened for their antibacterial properties and displayed low activity.     

The Biotransformation of 8-Chloro-6-phenyl-4H-s-triazolo[4, 3-a][1,4] benzodiazepine (D-40TA), a New Central Depressant,in Man,Dog and Rat

1. Metabolic studies of 8-chloro-6-phenyl-4H-^s-triazolo [4,3-a] [1,4] benzodiazepine (D—40TA) in man, dog and rat led to identification of the following metabolites: six hydroxylation products; 8-chloro-2,4-dihydro-6-phenyl-1H-s-triazolo[4,3-a] [1,4]benzodiazepin-1-one (I), 8-chloro-6-(4-hydroxyphenyl)-4H-s -triazolo[4,3-a][1,4]benzodiazepine (II), 8-chloro-6- (3-hydroxyphenyl)-4H-s-triazolo[4,3-a] [1,4] benzodiazepine (III), 8-chloro-4-hydroxy-6-phenyl-4H-s- triazolo[4,3-a][1,4]benzodiazepine (IV), 8-chloro-2,4-dihydro-6- (4-hydroxy-phenyl)-1H-s-triazolo[4,3-a] [1,4] benzodiazepin-1-one (V) and 8-chloro-2,4-dihydro-6-(3-hydroxyphenyl)- 1H-s- triazolo[4,3-a][1,4]benzodiazepin-1-one (VI); five ring-opened metabolites; 5-chloro-2-(4H-1,2,4-triazol-4-yl) -benzophenone (VII), 5-chloro-2- (2,3-dihydro-3-oxo- 4H -1,2,4- triazol-4-yl)benzophenone (VIII), 5-chloro-2- (2,3-dihydro-3-oxo-4H - 1,2,4-triazol-4-yl)-2-hydroxybenzophenone (IX), 5-chloro-2- (2,3-dihydro-3-oxo-4H-1,2,4-triazol-4-yl)-4'-hydroxybenzophenone (X) and 5-chloro-2-(3,5-dioxo-2,3,4,5-tetrahydro-1H-1,2,4-triazol-4-yl) benzophenone(XI).

2. In man, metabolites I, IV, VII and VIII are present as the free form in the urine, and I, II, IV and VIII are present as conjugates. In the dog, all the metabolites are present. The rat transforms the compound mainly to metabolites I, II, IV and V. None of the ring-opened metabolites are observed in the rat.     

Reactions with 4-Bromo-3-methyl-1-phenyl-2-pyrazolin-5-one: New Fused Pyrazole Derivatives

New furo[2,3-c]pyrazoles and pyrano[2,3-c]pyrazoles were synthesized from 4-bromo-3-methyl-1-phenyl-2-pyrazolin-5-one and active methylenenitriles, ethyl acetoacetate or phenylhydrazine. The constitutions of the new heterocycles were established by elemental analyses and spectroscopic data.     

Synthesis and properties of amides of 1-benzyl-3-methyl- and 1-butyl-3-phenyl-7-methyl-4-oxo-2-thioxo (2,4-dioxo)-1,2,3,4-tetrahydropyrido-[2,3-d]pyrimidine-6-carboxy lic acids

Amides of 1-benzyl-3,7-dimethyl-4-oxo-2-thioxo-1,2,3,4- tetrahydropyrido[2,3]pyrimidine-6-carboxylic acid were obtained by the condensation of ammonia, primary and secondary cyclic amines with the corresponding acid chloride. As by - products amides of 1-benzyl-3,7-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyr imidine-6- carboxylic acid were isolated as a result of desulfuration. The same reaction performed with chloride of 1-butyl-7-methyl-3-phenyl-4-oxo-2-thioxo-1,2,3,4-tetrahydropyri do[2,3- d]pyrimidine-6-carboxylic acid gave mainly the corresponding 2,4-dioxo-amides.     

Synthesis and biological evaluation of 6-(alkyn-1-yl)furo[2,3-d]pyrimidin-2(3H)-one base and nucleoside derivatives

Derivatives of the 2'-deoxynucleoside of furo[2,3-d]pyrimidin-2(3H)-one with long-chain alkyl (or 4-alkylphenyl) substituents at C6 exhibit remarkable anti-VZV (varicella-zoster virus) potency and selectivity, and analogous 2',3'-dideoxynucleoside derivatives show anti-HCMV (human cytomegalovirus) activity. We now report a synthetic approach that enables the preparation of long-chain 6-(alkyn-1-yl)furo[2,3-d]pyrimidin-2(3H)-ones in which the rodlike acetylene spacer replaces the 4-substituted-phenyl ring at C6. Analogues with methyl, beta-d-ribofuranosyl, beta-d-arabinofuranosyl, and 2-deoxy-beta-d-erythro-pentofuranosyl substituents at N3 have been prepared. Long-chain derivatives at C6 in the 2'-deoxynucleoside series showed virus-encoded nucleoside kinase-sensitive anti-VZV activity. Surprisingly, 3-methyl-6-(octyn-1-yl)furo[2,3-d]pyrimidin-2(3H)-one (prepared as a negative anti-VZV test control) exhibited anti-HCMV activity, which supports the possibility of development of non-nucleoside anti-HCMV agents originating from uncomplicated derivatives of such bicyclic ring systems.     

Non-steroidal antiinflammatory agents. Synthesis of novel 2-pyrazolyl-4(3H)-quinazolinones

Four novel series of pyrazolyl-4(3H)-quinazolinones have been prepared through the reaction of 3-aryl-2-hydrazino-4(3H)-quinazolinones with antipyrylazo-derivatives of ethyl acetoacetate, acetylacetone or diethyl malonate. These series of compounds are 3-aryl-2-[1-ethoxycarbonyl-1-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H - pyrazol-4-yl)hydrazono-2-propylidene]hydrazino-4(3H)-quinazo linones; 3-aryl-2-[4-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl) hydrazono-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl]-4(3H)-quinaz olinones; 3-aryl-2-[4-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)azo -3,5- dimethyl-1H-pyrazol-1-yl]-4(3H)-quinazolinones and 3-aryl-2-[4-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl) hydrazono-3,5-dioxo-pyrazolidin-2-yl]-4(3H)-quinazolinones. The antiinflammatory activity of some representatives of the prepared compounds was studied.     

Effects of protein kinase C inhibitors on thromboxane production by thrombin-stimulated platelets

The purpose of these studies was to identify a possible role for protein kinase C in thromboxane production. The effects of four putative protein kinase C inhibitors were studied with platelet stimulation by thrombin (0.5-150 nM), Thrombin Quick I (1.5-500 nM) or a thrombin receptor (protease activated receptor-1) agonist peptide (TRAP) (5-120 microM). Thromboxane production was increased by the bisindolylmaleimide derivative, 2-[1-(3-dimethylaminopropyl)-1H-indol-3-yl]-3-(1H-indol-3-yl)-maleimi de (GF 109203X), unchanged by the inhibitors 12-(2-cyanoethyl)-6,7, 12,13-tetrahydro-13-methyl-5-oxo-5H-indolo (2,3-a) pyrrolo (3, 4-c)-carbazole (G? 6976) and 5,21:12,17-dimetheno-18H-dibenzo[i, o]pyrrolo[3,4-l][1,8]diazacyclohexadecine-18,20(19H)-dione, 8-[(dimethylamino)methyl]-6,7,8,9,10,11-hexahydro-, monomethanesulfonate (379196), the latter of which is protein kinase C beta-selective, and decreased by 1-[6-[(3-acetyl-2,4, 6-trihydroxy-5-methylphenyl)methyl]-5,7-dihydroxy-2, 2-dimethyl-2H-1-benzopyran-8-yl]-3-phenyl-2-propen-1-one (rottlerin), an inhibitor selective for protein kinase C delta. These results indicate complex regulation of thromboxane synthesis in human platelets including a probable role for protein kinase C delta. The results taken together further suggest that GF 109203X may suppress negative feedback resulting from an unidentified kinase and that the classical protein kinase C isoforms alpha and beta do not have a significant role in regulating thromboxane production by platelets.     

苯并吡喃-4-腙类化合物的合成及其血管舒张活性

目的寻找高效低毒并具有组织选择性的苯并吡喃类钾通道开放剂。方法以对氰基苯酚为原料,经酰化、Fries重排、环合、成腙和取代等反应合成了3个系列20个苯并吡喃-4-腙类新化合物,所有目标化合物结构均经IR,1HNMR,MS和元素分析确证,并测定其对低钾(30 mmol·L^-1 KCl)和高钾(80 mmol·L^-1 KCl)诱导的大鼠主动脉条收缩抑制作用。结果合成了20个新化合物(I_1～9,II_1～4和III_1～7)。离体扩血管活性实验表明,大部分化合物具有一定的血管舒张活性。结论化合物I₉,III₂和III₅对低钾诱导的血管收缩抑制活性在1×10^-6 mol·L^-1浓度下略低于对照药emakalim,但对高钾诱导的血管收缩抑制活性在浓度为1×10^-5 mol·L^-1下强于对照药emakalim,值得进一步研究。     

Sesquiterpenoids from Ferula fukanensis and their inhibitory effects on nitric oxide production

Six sesquiterpene derivatives, 2,3-dihydro-7-methoxy-2S*, 3R*-dimethyl-2-[4,8-dimethyl-3(E),7-nonadienyl]furo[3,2-c]coumarin (1) and 2,3-dihydro-7-methoxy-2R*,3R*-dimethyl-2-[4,8-dimethyl-3(E),7-nonadienyl]furo[3,2-c]coumarin (2), nerolidol (3), 1-(2,4-dihydroxyphenyl)-3,7,11-trimethyl-3-ninyl-6(E),10-dodecadien-1-one (4), 1-(2,4-dihydroxyphenyl)-3,7-dimethyl-3-vinyl-8-(4-methyl-2-furyl)-6(E)-octen-1-one (5) and dshamirone (6) were isolated from an 80% aqueous methanol extract of the roots of Ferula fukanensis. The sesquiterpenoids inhibited nitric oxide (NO) production and inducible NO synthase gene expression by a murine macrophage-like cell line (RAW 264.7) [1], which was activated by lipopolysaccharide and recombinant mouse interferon-.     

A NEW ALKALOID FROM DYSOXYLUM BINECTARIFERUM

Two compounds (1 and 2) have been isolated from the stem bark of Dysoxylum binectariferum (Roxb.) Hook. f. ex Bedd. Compound 1 is rohitukine {5,7-dihydroxy-2-methyl-8-[4-(3-hydroxy-1-methyl)-piperidinyl]-4H-1-benzopyran-4-one}, a known compound that has anti-inflammatory and immunomodulatory activities. Compound 2 is a new alkaloid, named rohitukine N-oxide, the structure of which was elucidated on the basis of spectral evidences and comparison with the ¹H NMR data of rohitukine.