Synthesis of esters of phosphonoformic acid and their antiherpes activity

Aliphatic and aromatic mono-, di-, and triesters of phosphonoformic acid (foscarnet) were synthesized. The triesters were prepared by the Michaelis-Arbuzov reaction and were hydrolyzed to di- and monoesters. The compounds were tested for antiviral activity on isolated herpes simplex virus type 1 (HSV-1) DNA polymerase, in a HSV-1 plaque reduction assay, and on a cutaneous HSV-1 infection in guinea pigs. None of the esters inhibited the activity of isolated HSV-1 polymerases. Monoesters with a free carboxylic group and diesters with an aromatic carboxylic ester function were active against the cutaneous herpes infection. Mono- and diesters with an aromatic phosphonic ester group also showed activity in the plaque-reduction assay. However, mono- and diesters with an aromatic phosphonic ester group also showed activity in the plaque-reduction assay. However, mono- and diesters with aliphatic carboxylic ester groups were inactive in all test systems. The results show that all three acidic groups of phosphonoformic acid must be free in order to get antiviral activity at the enzyme level. However, certain esters of this acid may be biotransformed to the acid itself to give antiherpes activity.     

Two new constituents from mangrove Bruguiera gymnorrhiza

A lignan and two aromatic compounds were isolated from the branches of the mangrove plant, Bruguiera gymnorrhiza. They were brugunin A (1), bruguierol D (2) and 2,3-dimethoxy-5-propylphenol (3). Among them, 1 and 2 were new compounds; 3 was isolated from a natural source for the first time. The structures of these compounds were determined by NMR spectroscopic studies as well as chemical evidence.     

Two novel aromatic glucosides,marylaurencinosides D and E,from the fresh flowers of Cymbidium Great Flower ‘Marylaurencin’

Two novel aromatic glucosides, named marylaurencinosides D (1) and E (2), were isolated from the fresh flowers of Cymbidium Great Flower ‘Marylaurencin’. In addition, eight known aromatic compounds (3–10) were isolated. These structures were determined on the basis of NMR experiments as well as chemical evidence.     

Two new aromatic compounds from the resin of Styrax tonkinensis (Pier.) Craib

Two new aromatic compounds, trans-(tetrahydro-2-(4-hydroxy-3-methoxyphenyl)-5-oxofuran-3-yl)methyl benzoate (1), 3-(4-hydroxy-3-methoxyphenyl)-2-oxopropyl benzoate (2) and one new natural product, 4-((E)-3-ethoxyprop-1-enyl)-2-methoxyphenol (3) together with five known aromatic compounds have been isolated from the resin of Styrax tonkinensis (Pier.) Craib. Their structures were determined by physical and spectroscopic methods.     

Three new aromatic glycosides from the ripe fruit of cherry tomato

Three new aromatic glycosides were isolated from the ripe fruit of cherry tomato [Lycopersicon esculentum var. cerasiforme (Dunal) Alef. (Solanaceae)] along with six known aromatic glycosides and one known steroidal alkaloid glycoside. Their chemical structures were determined on the basis of spectroscopic data as well as chemical evidence.     

Biotransformation of 5-phenyl-1,3,4-benzotriazepines

After administration of three 2-aminosubstituted 5-phenyl-1,3,4-benzotriazepines with hypoglycemic effects to rats 10 metabolites were isolated from urine and feces besides traces of the unchanged drugs. N-Dealkylation, aromatic hydroxylation, N-acetylation and ring contraction by hydrolytic processes beginning in the stomach occurred. The main excretion route is with the feces.     

Synthesis, enantioseparation and pharmacological activity of 4-aryl-7,7-dimethyl-5-oxo-1,2,3,4,5,6,7,8-octahydroquinazoline-2-thiones

4-Aryl-7,7-dimethyl-5-oxo-1,2,3,4,5,6,7,8-octahydroquinazoline-2-thione derivatives (1-8) have been prepared by modified Biginelli reaction from 5,5-dimethyl-1,3-cyclohexanedione, the aromatic aldehydes and thiourea. The structures of the compounds were confirmed by spectroscopic and elemental analysis. Racemic compounds were resolved into their enantiomers by HPLC using an amylose tris-(3,5-dimethylphenylcarbamate) chiral stationary phase in the normal phase mode. The calcium antagonist activities of the compounds were determined by the tests performed on isolated rat ileum and lamb carotid artery. Compounds 2, 3, 4 and 6 were the most active compounds on isolated rat ileum. Compounds 2 and 3 were significantly active on lamb carotid artery.     

Two new constituents from mangrove Bruguiera gymnorrhiza

A lignan and two aromatic compounds were isolated from the branches of the mangrove plant, Bruguiera gymnorrhiza. They were brugunin A (1), bruguierol D (2) and 2,3-dimethoxy-5-propylphenol (3). Among them, 1 and 2 were new compounds; 3 was isolated from a natural source for the first time. The structures of these compounds were determined by NMR spectroscopic studies as well as chemical evidence.     

Anti-inflammatory activity of coumarins from Decatropis bicolor on TPA ear mice model

From the aerial parts of Decatropis bicolor, heraclenin (1), seselin (2), psoralen (3), imperatorin (4), skimmianine (5), and heraclenol (6), were isolated. This is the first time that coumarin-like compounds are isolated from Decatropis genus. The anti-inflammatory properties of compounds 1-6 were examined against the ear edema in mice produced by TPA. The results suggest that the anti-inflammatory activity of each compound depends of its individual substitution on the aromatic ring rather than the coumarin skeleton itself.     

Identification of etretinate metabolites in human blood

Five metabolites were isolated from the blood of psoriatic patients on chronic therapy with etretinate (Tegison). The two major metabolites were the all-trans acid (acitretin) and the 13-cis acid (isoacitretin), both of which had been previously identified as major metabolites of etretinate in human blood. The other three metabolites had not been previously reported in human blood. One metabolite corresponded to isoacitretin with a hydroxy group on an aromatic methyl group. The other two metabolites had acid side chains shortened by one carbon and a reduced 11, 12-double bond. One of the two metabolites retained the aromatic methoxy group, whereas the other was the phenolic analog.     

Urinary metabolites of a novel quinoxaline non-nucleoside reverse transcriptase inhibitor in rabbit, mouse and human: identification of fluorine NIH shift metabolites using NMR and tandem MS

1. The urinary metabolites of (S)-2-ethyl-7-fluoro-3-oxo-3,4-dihydro-2H-quinoxaline-carboxylic acid isopropylester (GW420867X) have been investigated in samples obtained following oral administration to rabbit, mouse and human. GW420867X underwent extensive biotransformation to form hydroxylated metabolites and glucuronide conjugates on the aromatic ring, and on the ethyl and isopropyl side-chains in all species. In rabbit urine, a minor metabolite was detected and characterized as a cysteine adduct that was not observed in mouse or man. 2. The hydroxylated metabolites and corresponding glucuronide conjugates were isolated by semi-preparative HPLC and characterized using NMR, LC-NMR and LC-MS/MS. The relative proportions of fluorine-containing metabolites were determined in animal species by 19F-NMR signal integration. 3. The fluorine atom of the aromatic ring underwent NIH shift rearrangement in the metabolites isolated and characterized in rabbit, mouse and human urine. 4. The characterization of the NIH shift metabolites in urine enabled the detection and confirmation of the presence of these metabolites in human plasma.     

Protection by uridine diphosphoglucuronic acid and DT-diaphorase against the cytotoxicity of polycyclic aromatic hydrocarbons isolated from a complex coal gasification condensate

The cytotoxicities of polycyclic aromatic hydrocarbon (PAH) subclasses isolated from a complex organic mixture (coal gasification condensate) were studied in vitro in Chinese hamster ovary cells, in the presence of rat liver microsomes from animals pretreated with Aroclor. Toxicity was enhanced by microsomal metabolism and was inversely related to aromatic ring number. Rat liver cytosol, semipurified DT-diaphorase, and uridine diphosphoglucuronic acid decreased the cytotoxicity of a variety of PAH mixtures and representative PAH, as well as individual PAH metabolites. The results indicate that the in vitro toxicity of complex PAH mixtures is caused primarily by hydroxy-PAH and quinone metabolites of the predominant, nonmutagenic two- and three-ring PAHs.     

深海链霉菌SCSIO 03032芳酰胺类代谢产物的研究

目的 对从印度洋深海沉积物中分离到的一株深海来源的放线菌Streptomyces sp. SCSIO 03032进行次级代谢产物分析及其活性研究。方法 对深海来源放线菌Streptomyces sp. SCSIO 03032的发酵产物进行有机溶剂萃取,利用正、反向硅胶层析、硅胶柱层析、凝胶柱层析、薄层层析等分离手段进行纯化,通过ESI-MS、₁H NMR、₁₃C NMR分析及文献查阅鉴定化合物结构,并对化合物进行抗菌及抗氧化活性研究。结果 从深海来源放线菌Streptomyces sp. SCSIO 03032的发酵产物中分离得到3个芳酰胺类化合物,其结构分别鉴定为4-甲基苯-1, 3-二氨基甲酸甲酯(1)、2-甲基苯-1, 3-二氨基甲酸甲酯(2)、羰基亚氨基4-甲基-3, 1-亚苯基双[氨基甲酸]甲酯(3);活性结果显示三个化合物均无明显的抑菌活性或抗氧化活性。结论 得到了一株能够产生3个不同芳酰胺类化合物的深海链霉菌SCSIO 03032。     

Aromatic constituents of Cymbidium Great Flower Marie Laurencin and their antioxidative activity

Two novel aromatic glucosides, named marylaurecinosides B (1) and C (2), were isolated from Cymbidium Great Flower Marie Laurencin, together with six known aromatic compounds (3–8). These structures were determined on the basis of NMR experiments as well as chemical evidence. All of the isolated compounds (1–8) were tested for antioxidative activity using a superoxide dismutase-like assay.     

Isolation, purification, and structure identification of glucuronic acid conjugates of propranolol and alprenolol and their ring-hydroxylated metabolites

The purpose of this study was to develop a procedure for the isolation, purification, and structure identification of glucuronic acid conjugates of propranolol and alprenolol and their active metabolites, 4-hydroxypropranolol and 4-hydroxyalprenolol. As both aliphatic and aromatic glucuronides may be formed from 4-hydroxypropranolol and 4-hydroxyalprenolol, the structure identification of these conjugates has to be based on the intact conjugates. Using DEAE-Sephadex anion-exchange chromatography, milligram quantities of these glucuronides were isolated from urine of dogs pretreated with propranolol and alprenolol, respectively. A high degree of purification was achieved by reversed-phase HPLC. Structure identification of the methyl ester-trimethylsilyl derivatives was accomplished by electron impact GC/MS. Only one 4-hydroxypropranolol glucuronide was found, having the glucuronic acid linked to the aromatic hydroxyl group. For 4-hydroxyalprenolol glucuronide, however, two structures were identified, one with the glucuronic acid linked to the aromatic hydroxyl group, and the other with the glucuronic acid linked to the aliphatic hydroxyl group of the side chain. Using this analytical approach, 4-hydroxypropranolol glucuronide was identified in the urine of patients on propranolol therapy. In man, as in the dog, only the aromatic glucuronide was found, i.e. containing an unsubstituted beta-blocking side chain.     

New aromatic esters from Galinsoga parviflora

Galinosoates A-C (1-3), new aromatic esters, have been isolated from the n-hexane soluble fraction of Galinsoga parviflora. Their structures were assigned from the spectral data including IR, HR-EI-MS, 1D and 2D NMR.     

Zur Darstellung von 5-Aryl-2-cyclohexenonen

Syntheses of 5-Aryl-2-cyclohexenones The 5-aryl-3-isopropyl-6,6-dimethyl-2-cyclohexenones 4a-f were synthesized by base-catalysed reactions of aromatic aldehydes with 3-methyl-2-butanone in ethanol/water at 70°C. Benzaldehyde and butanone react in the same way. Two of the four possible 5-aryl-2-cyclohexenones are formed in low yields and were isolated as their oximes.     

Constituents from Limonia Crenulata

A new indole alkaloid, crenulatine (1), along with twenty known compounds, was isolated from the stems of Limonia Crenulata. Their structures were identified by spectral means. Those compounds include four alkaloids, four coumarins, two flavanones, three tetranortriterpenoids, one triterpenoid, three steroids, two lignans and two aromatic compounds.     

Inhibition of rat platelet aggregation by a Prudhoe Bay crude oil and its aliphatic,aromatic, and heterocyclic fractions

Wasjed platelets isolated from rats 24 hr after oral treatment with a Prudhoe Bay crude oil (PBCO) showed a substantial inhibition of aggregation induced by ADP, arachidonic acid, or epinephrine. In vitro addition of a dimethyl sulfoxide extract of PBCO or its aliphatic, aromatic, or heterocyclic fractions to washed platelets also resulted in an inhibition of aggregation. ADP release was inhibited in platelets to which an extract of PBCO or its fractions were added in vitro or in platelets isolated from rats treated in vivo with PBCO. Thromboxane B₂ release was increased in platelets isolated from rats intubated with PBCO or in platelets to which a dimethyl sulfoxide extract of the aromatic or heterocyclic fraction was added. However, thromboxane B₂ release was inhibited in platelets to which PBCO or the aliphatic fraction extracts were added. The results indicate that PBCO inhibits platelet aggregation presumably by bringing about alterations in the platelet plasma membrane. Inhibition of ADP release could contribute to the inhibition of aggregation but thromboxane B₂ is believed not to play a significant role.     

Urinary metabolites of a novel quinoxaline non-nucleoside reverse transcriptase inhibitor in rabbit,mouse and human: identification of fluorine NIH shift metabolites using NMR and tandem MS

1. The urinary metabolites of (S)-2-ethyl-7-fluoro-3-oxo-3,4-dihydro-2H-quinoxaline-carboxylic acid isopropylester (GW420867X) have been investigated in samples obtained following oral administration to rabbit, mouse and human. GW420867X underwent extensive biotransformation to form hydroxylated metabolites and glucuronide conjugates on the aromatic ring, and on the ethyl and isopropyl side-chains in all species. In rabbit urine, a minor metabolite was detected and characterized as a cysteine adduct that was not observed in mouse or man. 2. The hydroxylated metabolites and corresponding glucuronide conjugates were isolated by semi-preparative HPLC and characterized using NMR, LC-NMR and LCMS/MS. The relative proportions of fluorine-containing metabolites were determined in animal species by ¹⁹F-NMR signal integration. 3. The fluorine atom of the aromatic ring underwent NIH shift rearrangement in the metabolites isolated and characterized in rabbit, mouse and human urine. 4. The characterization of the NIH shift metabolites in urine enabled the detection and confirmation of the presence of these metabolites in human plasma.