Synthesis of N-[(3S)-2,6-dioxo-1-(2-phenylethyl)-3-piperidinyl]-(2S)-2-methylbutanamide ((-)-julocrotine)

The total synthesis of (-)-julocrotine (1) starting from l-glutamic acid in 41% overall yield is described. The methodology utilizes protection, deprotection, and regioselection (carbonyl differentiation via oxazolidinone) protocols, and glutarimide ring formation is the key step.     

Efficient total synthesis of (+)-dihydropinidine, (-)-epidihydropinidine, and (-)-pinidinone

The 2,6-disubstituted piperidine alkaloids (+)-dihydropinidine (1), (-)-epidihydropinidine (2) (as HCl salts), and (-)-pinidinone (3) were efficiently synthesized from (S)-epichlorohydrin (7) as common substrate using regioselective Wacker-Tsuji oxidation of alkenylazides 10 and 14 as well as a highly diastereoselective reduction of cyclic imine 11 as key steps. The protecting group free total syntheses represent the up to date shortest routes with highest overall yields for all three naturally occurring alkaloids (1-3). The first single-crystal X-ray analysis of (-)-epidihydropinidine hydrochloride (2·HCl) confirmed its proposed absolute configuration to be (2S,6S), corresponding to that of the isolated natural product.     

Expedient synthesis of (S)- and (R)-norcoclaurine from (S)- and (R)-norarmepavine [corrected] prepared by the 1-phenylethylurea method

(+/-)-Norarmepavine [3] [corrected] prepared by Bischler-Napieralski synthesis afforded, on reaction with (S)-(-)-1-phenylethylisocyanate, ureas 4 and 5 which were separated and purified by crystallization from EtOH and 70% HOAc. Alcoholysis of 4 and 5 with sodium butoxide in n-BuOH afforded (S)-norarmepavine [3a] and (R)-norarmepavine [3b] [corrected], respectively. Hplc analysis of ureas prepared from 3a and 3b with (S)-(-)-1-phenylethylisocyanate showed them to be optically pure alkaloids. Refluxing 3a and 3b with 48% HBr afforded the hydrobromide salts of (S)-norcoclaurine [1a] and its (R)-isomer 1b, respectively.     

Effect of phytochemicals on the mutagenicity of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in Salmonella typhimurium strain TA1535

Five phytochemicals with potential chemopreventive activity were tested to determine their antimutagenic effects toward the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in Salmonella typhimurium strain TA1535. NNK at a concentration of 80 mM was metabolically activated by hamster liver microsomes. Three phytochemicals; capsaicin, diallyl sulphide and silymarin, exhibited antimutagenic activity toward NNK in a dose-dependent manner. At the highest nontoxic concentration tested (0.5 mmole/plate), the inhibitory effect of capsaicin, diallyl sulphide and silymarin was 85%, 23% and 48%, respectively. D-limonene and tannic acid were also tested but did not show antimutagenic activity toward NNK in TA1535. These results suggest that capsaicin, diallyl sulphide and silymarin inhibited the activation of NNK and indicate that further studies of the efficacy of these phytochemicals in the chemoprevention of NNK-induced carcinogenesis are warranted.     

Effect of (+/-)-, (+)- and (-)-gossypol on the lactate dehydrogenase-X activity of rat testis

The effect of (+/-)-, (+)- and (-)-gossypol on testicular lactate dehydrogenase-X (LDH-X) was studied in vitro and in vivo. It was found that racemic gossypol and the two optical enantiomers had similar inhibitory effects on rat testicular LDH-X in vitro. However, neither racemic gossypol nor the enantiomers exhibited an inhibitory effect on testicular LDH-X in vivo. It is concluded that inhibition of testicular LDH-X is not likely to be the mechanism of the antifertility action of gossypol. The inhibition of testicular LDH-X in vitro by all three preparations of gossypol is probably non-specific.     

(E)-2-[2-(4-甲氧苄基)肼基]-4-苯基噻唑与人血清蛋白的相互作用

目的: 研究(E)-2-[2-(4-甲氧苄基)肼基]-4-苯基噻唑(MHP)与人血清蛋白(HSA)之间的相互作用,为揭示噻唑类衍生物与DNA作用的机制提供实验依据. 方法: 根据MHP与HSA相互作用的荧光敏化作用,利用Stern-Volmer方程,及非辐射能量转移理论处理实验数据,采用同步荧光光谱探讨了MHP对HSA构象的影响. 结果: 实验发现MHP可以使HSA的荧光增强,表明两者之间发生了能量转移,能量转移的机理是MHP与HSA结合形成了复合物.荧光增强(敏化)效应主要源于给体-受体间的偶极-偶极作用的能量转移. 结论: 能量转移的结果为内原发色基团的荧光被猝灭和外源发色基团荧光被敏化,计算得到其敏化常数为-2.620 8×10⁴.同步荧光光谱表明,相互作用引起HSA构象变化,提示结合位点更接近于色氨酸.     

Enantioselective synthesis of the tetrahydrofuran lignans (-)- and (+)-magnolone

The optically pure trisubstituted 7'-oxotetrahydrofuran lignans (-)- and (+)-magnolone ( 1) were synthesized by employing stereoselective S N1 intramolecular cyclization as a key reaction. The absolute configuration of naturally occurring (-)-magnolone was determined as (7 S,8 R,8' S).     

Stereoselective synthesis of (+)-11betaH,13-dihydroestafiatin, (+)-11betaH,13-dihydroludartin, (-)-compressanolide,and (-)-11betaH,13-dihydromicheliolide from santonin

Starting from 2 and 3, obtained from santonin (1), we have synthesized natural guaianolides 4-7. Chemoselective epoxidation of 2 gave (+)-11betaH,13-dihydroestafiatin (4), and epoxidation of 3 followed by regioselective elimination of the hydroxyl group afforded (+)-11betaH,13-dihydroludartin (5). Sharpless' mild regioselective ring-opening of 4 and 5 followed by hydrogenolysis yielded (-)-compressanolide (6) and (-)-11betaH,13-dihydromicheliolide (7), respectively.     

没食子儿茶素促进脂肪细胞吸收葡萄糖研究

目的探讨没食子儿茶素对脂肪细胞在高浓度葡萄糖条件下吸收葡萄糖的作用。方法应用3T3-L1前脂肪细胞分化模型,测定在脂肪细胞中没食子儿茶素对葡萄糖吸收的作用和对3T3-L1前脂肪细胞分化的影响。结果没食子儿茶素可促进脂肪细胞中高浓度葡萄糖(30 mmol/L)条件下由胰岛素刺激的葡萄糖吸收,加快3T3-L1前脂肪细胞的分化。结论没食子儿茶素可增加脂肪细胞葡萄糖吸收并促进3T3-L1前脂肪细胞分化,提示没食子儿茶素可有效改变血糖浓度和改善胰岛素抵抗。     

7-(香豆素-3-甲酰胺)-3-[1-(取代）吡啶基甲基]头孢菌素的合成

 目的：探讨3'-乙酰氧基被N-7亲核试剂取代的反应条件、分离精制方法和新头孢菌素的体外抗菌活性。方 法：7-(香豆素-3-甲酰胺)头孢菌素在Nal或KSCN的存在下与吡啶和β-甲基吡啶反应，产物用大孔吸附树脂及葡 聚糖凝胶柱层析分离。结果：合成的二个新头孢菌素化合物，由红外光谱、元素分析和核磁共振谱确证其化学结构。体外抗菌试验表明，对某些革兰阴性菌有一定的抑菌作用。结论：该反应中加入大量的Nal可缩短短反应时间并减少杂质。大孔吸附树脂可有效果将头孢菌素与无机盐分离。     

Antioxidative effects of 7-hydroxy-3-methoxy-cadalene extracted from Zelkova serrata on 4-(methylinitros amino)-1-(3-pyridyl)-1-butanone-induced oxidative stress in A/J mice

Effects of 7-hydroxy-3-methoxy-cadalene (cadalene) extracted from Zelkova serrata on 4-(methylinitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced oxidative stress were examined using A/J mice. NNK (65 microg/ml water) was orally administered to 20 mice for 7 weeks, followed by free feeding of a commercial diet, not containing cadalene, for 2 weeks. The control group was maintained without NNK and cadalene administration, and treatment groups with NNK and cadalene (6.25, 25, 100 mg/kg feed) feeding for 25 weeks. The glutathione concentration of cadalene-treated (65 microg/ml water) group was significantly higher than that of the group treated only with NNK (p < 0.05). The results of our study strongly indicate that cadalene exerts antioxidative effect on NNK-induced lung tumorigenesis in A/J mice.     

Biosynthesis of the defensive alkaloid (Z)-3-(2-methyl-1-butenyl)pyridine in Stenus similis beetles

Most rove beetles of the genus Stenus protect themselves against microorganisms and predators such as ants and spiders by producing the alkaloid stenusine (1) in their pygidial glands. The biosynthesis of 1 was previously investigated in S. bimaculatus, where L-lysine forms the piperidine ring, L-isoleucine the side chain, and acetate the N-ethyl group. In addition to 1, S. similis keeps the pyridine alkaloid (Z)-3-(2-methyl-1-butenyl)pyridine (2) in its pygidial glands. Feeding S. similis beetles with [D,15N]-labeled amino acids followed by GC/MS analysis showed that L-Lys yields the pyridine ring and L-Ile the 2-methyl-1-butenyl side chain. Thus the alkaloids 1 and 2 probably share two precursor molecules in their biosynthesis.     

(-)-delta-N-normethylskytanthine from Tecoma arequipensis

Bark of Tecoma arequipensis yielded the major alkaloidal component (-)-delta-N-normethylskytanthine whose structure was proven by X-ray diffraction analysis of the N-thiourea derivative. The stereochemistry of 1 at all four centers was enantiomeric with that of skytanthine previously reported from Tecoma stans and Skytanthus acutus. Gc-ms of the crude base fraction indicated the presence of several related alkaloids as very minor constituents.     

Active components from Artemisia iwayomogi displaying ONOO(-) scavenging activity

Peroxynitrite (ONOO(-)) is one of cytotoxic species produced by the reaction between superoxide (*O(2) (-)) and nitric oxide (NO). The main aim of this study was to identify ONOO(-) scavenging constituents from herbs. Methanolic extracts derived from one hundred thirty eight herbs were screened out for their ONOO(-) scavenging activities. Twenty herbs showed excellent ONOO(-) scavenging activity in a dose dependent manner. Of them, Artemisia iwayomogi, which showed the highest activity, was fractioned with several solvents. The ONOO(-) scavenging activity of fractions was in order of ethyl acetate (EtOAc) > n-butanol (BuOH) > dichloromethane (CH(2)Cl(2)) > water (H(2)O) fraction. The EtOAc and the n-BuOH fractions were further purified to isolate active principles by column chromatography. Apigenin 7-methylether (genkwanin), apigenin 7,4'-di-O methylether, jaceosidin, and scopoletin from the EtOAc fraction and chlorogenic acid, 2,4-dihydroxy 6-methoxy acetophenone 4-O-beta-D-glucoside, quebrachitol, and scopolin from the n-BuOH fraction were identified. The scavenging activities of chlorogenic acid (IC(50) = 0.52 +/- 0.04 microM), genkwanin (IC(50) = 1.01 +/- 0.10 microM), and scopoletin (IC(50) = 1.03 +/- 0.15 micro M) were higher than or comparable to a well-known ONOO(-) scavenger, penicillamine (IC(50) = 1.76 +/- 0.18 microM), suggesting that those compounds might be developed as effective ONOO(-) scavengers for, prevention of the ONOO(-)-involved diseases.     

Effect of (-)- and (+)-gossypol on fertility in male rats

(+)-Gossypol has neither antifertility effect nor toxicity at the dosage of 30 mg/kg orally for 14 days in male rats, but slight damage was found in the germinal epithelium of the testis in animals dosed for 4 weeks. (-)-Gossypol at 30 mg/kg orally for 7 days clearly had an antifertility effect in male rats. It appears that (-)-gossypol is the active stereoisomer of racemic gossypol.     

(+)- and (-)-syn-2-isobutyl-4-methylazetidine-2,4-dicarboxylic acids from the extract of Monascus pilosus-fermented rice (red-mold rice)

The structures of two enantiomeric azetidine-type amino acids isolated from the n-butanol-soluble fraction of the 70% ethanol extract of red-mold rice fermented with Monascus pilosus were established to be (+)- [1; (+)-monascumic acid] and (-)-syn-2-isobutyl-4-methylazetidine-2,4-dicarboxylic acids [2; (-)-monascumic acid] based on spectroscopic methods.     

Neuroprotective 2-(2-phenylethyl)chromones of Imperata cylindrica

Bioactivity-guided fractionation of the methanolic extract of the rhizomes of Imperata cylindrica afforded a new compound, 5-hydroxy-2-(2-phenylethyl)chromone (1), together with three known compounds, 5-hydroxy-2-[2-(2-hydroxyphenyl)ethyl]chromone (2), flidersiachromone (3), and 5-hydroxy-2-styrylchromone (4). Among these four compounds, 1 and 2 showed significant neuroprotective activity against glutamate-induced neurotoxicity in primary cultures of rat cortical cells.     

Absolute configuration of (-)-gambogic acid, an antitumor agent

(-)-Gambogic acid (1), a biologically active "caged xanthone" from gamboge, the dried resin of Garcinia hanburyi, is of interest as a potential anticancer agent. The planar structure of (-)-gambogic acid has been determined previously by analysis of its detailed NMR data and confirmed by single-crystal X-ray diffraction, with the absolute configuration at C-13 deduced as R through a series of chemical degradations. Using (-)-morellic acid (2), an analogue of (-)-gambogic acid, as a model compound, the 5R, 7S, 10aS, 13R, 27S absolute configuration of (-)-gambogic acid was determined for the first time by comparison of physical and spectroscopic data, especially experimental and calculated electronic circular dichroism.     

(-)-agelasidine C and (-)-agelasidine D, two new hypotaurocyamine diterpenoids from the Caribbean sea sponge Agelas clathrodes.

Two new diterpene derivatives of hypotaurocyamine, (-)-agelasidine C [3] and (-)-agelasidine D [5], have been isolated from the Caribbean sea sponge Agelas clathrodes. The structures of 3 and 5 have been established by interpretation and comparison of their spectral data to those of the known antipode (+)-agelasidine C [1].     

丹参素异丙酯对大鼠肺动脉平滑肌的作用

目的：研究丹参素异丙酯对离体血管平滑肌的作用。方法：制备大鼠肺动脉条，采用离体血管灌流方法，观察丹参素异丙酯对去甲肾上腺素(NE)预收缩动脉的舒张作用以及对多种血管收缩药量效曲线的影响。结果：丹参素异丙酯可浓度依赖性舒张NE预收缩的完整内皮血管，去内皮后该作用明显降低；对5-羟色胺(5-HT)、内皮素(ET-1)，U46619和KCl量效曲线均表现浓度依赖性抑制。结论：丹参素异丙酯可内皮依赖性地舒张大鼠肺动脉，机制可能与调节钙通道活动有关。