氯胺酮

Part 2. Annulation reaction of 3, 4-dichlorocoumarin (1) and 3, 4-dichloromaleimide (8) by a new general annulation strategy developed in this group with 2-phenylbenzofuran (15), 3-phenylbenzofuran (16), 2, 5-diphenyloxazole (17), 2, 5-diphenylthiazole (18), 2-methyl-4-phenylthiazole (19) and 2, 3-dimethoxy-1, 3-butadiene (40) were investigated.

二。在本课题组前一阶段提出的从二氯代环烯酮与1，1-二芳基乙烯的光化反应以及光化反应中得到的环丁烷产物的连续电环化反应对3，4-二氯马来酰亚胺以及3，4-二氯香豆素进行增环反应的工作基础上，研究了3，4-二氯香豆素（1）和3，4-二氯马来酰亚胺（8）与5个α-苯基取代的环烯烃2-苯基苯并呋喃（15），3-苯基苯并呋喃（16），2，5-二苯基噁唑（17），2，5-二苯基噻唑（18），2-甲基-4-苯基噻唑（19），以及一个丁二烯——2，3-二甲氧基丁二烯（40）进行的芳香族增环反应。

They are 4-(2- hydroxy-3-butynlenoxy) benzoic acid (1, WA), 5-chloro-7, 8-dihydroxy-7-methyl- 6-oxo-3- [ -3, 4-dihydroxy-3, 5-dimethyl-l-heptylene] -1H-8, 8a-dihydrobenzo [2, 3-c] pyran (2, WB),-2-(2-methyl-2-dibutene diamido)-2-butenoic acid (3, B5262), 3, 4-dihydro-9, 10-dihydroxy-7-methoxy-3-methyl-1H-naphtho [2, 3- c] pyran-1-one (4, A73 semi-Vioxanthin), 8, 8'-bis (6, 9-dioxo-3,4-dihydro-10- hydroxy-7-methoxy-3-methyl-1H-naphtho [2, 3-c] pyran-1-one)(5, A122 Xanthomegnin), 2, 5-dioxo-3a-hydroxymethyl-3, 3a, 6, 6a-tetrahydro-furo [2, 3-b] furan (6, 1003-2), 7-acety1-5-chloro-6, 8-dioxo-7-methyl-3- [ -3, 5-dimethyl-1, 3- diheptylene] -4aH-benzo [2, 3-c] pyran (7, M2-2 sclerotiorin), respectively.

它们分别被命名为4-（2-羟基-3-丁炔氧基）苯甲酸（1，WA）、5-氯-7，8-二羟基-7-甲基-6-氧代-3-[-3，4-二羟基-3，5-二甲基-1-庚烯基]-1H-8，8a-二氢苯并[2，3-c]吡喃（2，WB）、-2-（2-甲基-2-丁烯二酰亚胺基）-2-丁烯酸（3，B5262）、3，4-氢-9，10-二羟基-7-甲氧基-3-甲基-1H-萘并［2，3-c］吡喃-1-酮（semi-Vioxanthin，4，A73）、8，8'-双（6，9-二氧代-3，4-二氢-10-羟基-7-甲氧基-3-甲基-1H-萘并［2，3-c］吡喃-1-酮）（Xanthomegnin，5，A122）、2，5-二氧代-3a-羟甲基-3，3a，6，6a-四氢-呋喃并［2，3-b］呋喃（6，1003-2），7-乙酰基-5-氯-6，8-二氧代-7-甲基-3-［-3，5-二甲基-1，3-庚二烯基］-4aH-苯并2，3-c］吡喃（Sclerotiorin，7，M2-2）。

When the catalyst was triethylamine, the water produced in condensation of isopropanolamine or ethanolamine and butanone was removed with benzene by water segregator, then the dichloroacetyl chloride was dropped.

利用异丙醇胺、乙醇胺、丁酮和二氯乙酰氯为原料，分别合成了两种除草剂安全剂Ⅰ∶3-二氯乙酰基-2，5-二甲基-2-乙基-1，3-噁唑烷和Ⅱ∶3-二氯乙酰基-2-甲基-2-乙基-1，3-噁唑烷。

Using a phase equilibrium apparatus, the solubilities of anthracene and carbazole in dimethyformamide, N-methylpyrrolidinone, cyclohexanone, xylene, dichloroethane and tetrachloroethylene were determined and solubility curves were drawn, providing useful data for crude anthracene processing.

利用液固相平衡实验装置，测定了蒽和咔唑在二甲基甲酰胺、N-甲基吡咯烷酮、环己酮、二甲苯、二氯乙烷和四氯乙烯中的溶解度，并作出溶解度曲线，为粗蒽的分离和精制提供了有用数据。

Amino-6-methoxy Benzothiazole 99%、2-Amino Benzothiazole 99%、Veratraldehyde 99%、Veratric Acid 99%、1,2- Dimethoxy Benzene 99%、6-Nitroveratric Acid 97%、2,5-Dichlorobenzoic Acid 99%、4-Chloro-3-Nitrobenzoic Acid 99%、 3-Nitrobenzole Acid 98%、p-Methoxybenzoie Acid 99%、Anisole 99.5%、p-Methoxyacetophenonc 99%、(2'-Chloroethyl) Benzene 99%、(2'-Bromoethyl) Benzene 99%、N,N-Diethyi-m-Toiuamide 99%、Aminoacetonitrile Hydrochloride 98%、 Alkyl Diphenyl Phosphate Estrel 98%、5-Chloro-2-benzothiazolone 99%、6-bromo-2-naphthol 98%、6-Nitro-Veretric Acid Estrel 97%、4-chloro phenoxyaeetic 99

2-氨基-6-甲氧基苯骈噻唑、2-氨基苯骈噻唑、藜芦醛、藜芦酸、藜芦醚、6-硝基藜芦酸、2，5-二氯苯甲酸、3-硝基-4-氯苯甲酸、3-硝基苯甲酸、对甲氧基苯甲酸、苯甲醚、对甲氧基苯乙酮、β-氯代苯乙烷、β-溴代苯乙烷、N，N-二乙基间甲苯甲酰胺、氨基乙腈盐酸盐、磷酸二苯月桂酯、5-氯-2-苯骈噻唑酮、6-溴-2-萘酚、6-硝基藜芦酸甲酯、4-氯苯氧乙酸

Our company supply raw materials and related intermediates as follows: Second dibutyryl cAMP calcium, voriconazole, terbinafine, vecuronium amines, cAMP, thiamphenicol, a chlorophenol hydrochloride esters, card network sodium phosphate tilmicosin, foscarnet, lornoxicam, Tilmicosin, Cephalosporium aspirin acid, ceftiofur hydrochloride, ceftiofur sodium, Ozagrel, ondansetron hydrochloride ketones, hydroxyurea, ticarcillin sodium, telmisartan, esmolol hydrochloride, hydrochloric acid Daguan Nikkomycin, adefovir dipivoxil, buflomedil hydrochloride, granisetron hydrochloride, warfarin sodium,-methyl gabexate acid, nicergoline, pantoprazole sodium,·, tegafur, cefepime hydrochloride, vecuronium bromide, hydrochloric acid meclofenoxate, sertraline hydrochloride, Cefonicid amine salt, aztreonam, ticarcillin, cefdinir, cefodizime sodium, sodium ferulate, colloidal pectin secretion, 2,3 - cyclopentene and pyridine, Piperacillin acid, cefetamet US-acid, hydrochloride Cefmenoxime ,3-TZ, 2 - deoxy-D-glucose, two-amidine urea benzene, sodium Cefonicid, Cefonicid intermediates, ester Cefamandole sodium, Cefalotin acid, intermediates cefpirome, cefepime sulphate, cefepime intermediate nucleus of cefepime, cefpirome nucleus, Cefamandole sodium, ceftriaxone new active ester, oxaliplatin, cyclophosphamide vary gland amines, polyene match him.

我公司供应的原料药及相关中间体为：二丁酰环磷腺苷钙、伏立康唑、盐酸特比萘芬、维库溴胺、环磷腺苷、甲砜霉素、盐酸甲氯酚酯、卡络磺钠、磷酸替米考星、膦甲酸钠、氯诺昔康、替米考星、头孢匹胺酸、头孢噻呋盐酸盐、头孢噻呋钠、奥扎格雷、盐酸恩丹西酮、羟基脲、替卡西林钠、替米沙坦、盐酸艾司洛尔、盐酸大观霉素、阿德福韦酯、盐酸丁咯地尔、盐酸格拉司琼、华法林钠、甲磺酸加贝酯、尼麦角林、泮托拉唑钠、普拉洛芬、替加氟、盐酸头孢吡肟、维库溴铵、盐酸甲氯芬酯、盐酸舍曲林、头孢尼西胺盐、氨曲南、替卡西林、头孢地尼、头孢地嗪钠、阿魏酸钠、胶体果胶泌、2，3-环戊烯并吡啶、哌拉西林酸、头孢他美酸、头孢甲肟盐酸盐、3-TZ、2-脱氧-D-葡萄糖、双脒苯脲、头孢尼西钠、头孢尼西中间体、头孢孟多酯钠、头孢噻吩酸、头孢匹罗中间体、头孢吡肟硫酸盐、头孢吡肟中间体、头孢吡肟母核、头孢匹罗母核、头孢孟多钠、头孢曲松新型活性酯、奥沙利铂、异环磷腺胺，多烯他赛。

Firstly, 3-ethylthiobutanal was prepared from crotonaldehyde reacting with ethanehiol in triethylamine with high yield. Secondly, methyl acetoacetate was converted to 6-ethylthiohept-3-en-2-one by three steps via hydrolysis, condensation with 3-ethyltio-butanal and dehydration, then 6-ethylthiohept-3-en-2-one was cycloco ndensed with dimethyl malonate by Michael addition and Claisen condensation, followed by saponification and decarboxylation to give the intermediate of 5-(2-ethylthiopropyl)-cyclohexane-1,3-dione.

首先，以巴豆醛与乙硫醇为原料，在三乙胺的催化作用下高收率制得3-乙硫基丁醛；然后从乙酰乙酸甲酯出发，通过碱水解、与3-乙硫基丁醛缩合、脱水三步反应合成6-乙硫基-3-烯-2-庚酮，接着6-乙硫基-3-烯-2-庚酮与丙二酸二甲酯通过Michael加成和Claisen缩合成环，再通过皂化和脱羧反应生成中间体5-[2-丙基]-1，3-环己二酮；再与丙酸酐反应丙酰化，最后与0-3-氯-2-丙烯基羟胺肟化，得到目标化合物烯草酮。

Then sodium ethoxide was used as base,the nucleophilic substitution of 2-pyrrolidone with the intermediate provided nefiracetam.

以碳酸钠为缚酸剂，摩尔比为1︰1的2，6-二甲基苯胺与氯乙酰氯反应合成了中间体2-氯-N-(2，6-二甲基苯基)乙酰胺；在强碱乙醇钠作用下，2-吡咯烷酮再与2-氯-N-(2，6-二甲基苯基)乙酰胺经亲核取代合成了目标化合物奈非西坦。

A plausible process of this reaction is as following: Aldehyde was in equilibrium with the enol form, aldehyde reacted with aniline catalyzed by 2,2,2-trichloroacetic acid to afford imine, the generated imine immediately reacted with enol to form intermediate via intramolecular cyclization.

我们发现一分子芳基叠氮和一分子三苯基磷反应生成一分子磷亚胺，后者与由两分子取代的苯氧乙酰氯原位生成的烯酮反应生成4-亚烷基-β-烷基-内酰胺，其串联过程涉及烯酮亚胺的形成及其与烯酮的[2+2]的环加成反应。

The effects and mechanism of GABAergic neurons, NOergic neurons, opioid peptide and cyclic adenosine monophosphate in the nucleus reticularis thalami on sleep-wakefulness cycle of rats and the effects and mechanism of the 5-HTergic nerve fibers project from the nucleus raphes dorsalis to RT on sleep-wakefulness cycle of rats were investigated with the methods of brain stereotaxic, nucleus spile, microinjection and polysomngraphy.1. The effects of GABAergic neurons in RT on sleep-wakefulness cycle of rats1.1 Microinjection of 3-mercaptopropionic acid (3-MP, a kind of glutamate decarboxylase inhibitor) into RT. On the day of microinjection, sleep only decreased a litter. On the second day, sleep marked decreased and wakefulness marked increased. On the third and fourth day, sleep and wakefulness stages resumed to normal.1.2 Microinjection of gamma-amino butyric acid (GABA 1.0μg) into RT enhanced sleep and reduced wakefulness compared with control; while microinjection of L-glutamate (L-Glu, 0.2μg) decreased sleep and increased wakefulness; microinjection of bicuculline (BIC, 1.0μg), a GABAA receptor antagonist, enhanced wakefulness and reduced sleep; microinjection of baclofen (BAC, 1.0μg), GABAB receptor agonist, had the same effects as GABA.2. The effects of NOergic neurons in RT on sleep-wakefulness cycle of rats2.1 Microinjection of L-arginine (L-Arg, 0.5μg) into RT decreased sleep compared with control, but there were on statistaical difference between L-Arg group and control; while microinjection of sodium nitroprusside (SNP, 0.2μg), a NO donor into RT, sleep marked decreased and wakefulness marked increased. Microinjection of nitric oxide synthase inhibitor, N-nitro-L-arginine (L-NNA, 2.0μg) into RT enhanced sleep and reduced wakefulness.2.2 After simultaneous microinjection of L-NNA (2.0μg) and SNP (0.2μg) into RT, SNP abolished the sleep-promoting effect of L-NNA compared with L-NNA group; after simultaneous microinjection of L-NNA (2.0μg) and L-Arg(0.5μg) into RT, we found that L-NNA could not blocked the wakefulness-promoting effect of L-Arg.3. The effects of opioid peptide in RT on sleep-wakefulness cycle of rats3.1 Microinjection of morphine sulfate (MOR, 1.0μg) into RT increased wakefulness and decreased sleep compared with control; while microinjection of naloxone hydrochloride (NAL, 1.0μg), the antagonist of opiate receptors, into RT, enhanced sleep and reduced wakefulness.3.2 After simultaneous microinjection of MOR (1.0μg) and NAL (1.0μg) into RT, the wakefulness-promoting effect of MOR and the sleep-promoting effect of NAL were not observed compared with control.4. The effects of cAMP in RT on sleep-wakefulness cycle of rats Microinjection of cAMP (1.0μg) into RT increased sleep and decreased wakefulness compared with control; microinjection of methylene blue (MB,1.0μg) into RT enhanced sleep and reduced wakefulness compared with control.5. The effects of the 5-HTergic nerve fibers project from DRN to RT on sleep-wakefulness cycle of rats5.1 When L-Glu (0.2μg) was microinjected into DRN and normal sodium (NS,1.0μg) was microinjected into bilateral RT. We found that sleep was decreased and wakefulness was increased compared with control; when L-Glu (0.2μg) was microinjected into DRN and methysergide (MS,1.0μg), a non-selective 5-HT antagonist, was microinjected into bilateral RT, We found that sleep was enhanced and wakefulness was reduced compared with L-Glu group.5.2 When p-chlorophenylalanine (PCPA, 10μg) was microinjected into DRN and NS (1.0μg) was microinjected into bilateral RT, We found that sleep was increased and wakefulness was decreased compared with control; microinjection of 5-hydroxytryptaphan (5-HTP, 1.0μg), which can convert to 5-HT by the enzyme tryptophane hydroxylase and enhance 5-HT into bilateral RT, could block the effect of microinjection of PCPA into DRN on sleep-wakefulness cycle.

本研究采用脑立体定位、核团插管、微量注射、多导睡眠描记等方法，研究丘脑网状核(nucleus reticularis thalami，RT)中γ-氨基丁酸(gamma-amino butyric acid ，GABA)能神经元、一氧化氮(nitrogen monoxidum，NO)能神经元、阿片肽类神经递质、环一磷酸腺苷(cyclic adenosine monophosphate，cAMP)及中缝背核(nucleus raphes dorsalis，DRN)至RT的5-羟色胺(5-hydroxytryptamine，5-HT)能神经纤维投射对大鼠睡眠-觉醒周期的影响及其作用机制。1 RT内GABA能神经元对大鼠睡眠-觉醒周期的影响1.1大鼠RT内微量注射GABA合成关键酶抑制剂3-巯基丙酸(3-MP，5μg)，注射当天睡眠时间略有减少，第二日睡眠时间显著减少，觉醒时间明显增多，第三、四日睡眠和觉醒时间逐渐恢复至正常。1.2大鼠RT内微量注射GABA受体激动剂GABA( 1.0μg)后，与生理盐水组比较，睡眠时间增加，觉醒时间减少；而RT内微量注射L-谷氨酸(glutamic acid， L-Glu， 0.2μg)后，睡眠时间减少，觉醒时间增加；RT内微量注射GABAA受体阻断剂荷包牡丹碱(bicuculline，BIC，1.0μg)后，睡眠时间减少，觉醒时间增加；RT内微量注射GABAB受体激动剂氯苯氨丁酸(baclofen，BAC，1.0μg)后，产生了与GABA相似的促睡眠效果。2 RT内NO能神经元对大鼠睡眠-觉醒周期的影响2.1大鼠RT内微量注射NO的前体L-精氨酸(L-Arg，0.5μg)后，与生理盐水组对比，睡眠时间略有减少，但无显著性意义；而RT内微量注射NO的供体硝普钠(Sodium Nitroprusside，SNP，0.2μg)后可明显增加觉醒时间，缩短睡眠时间；微量注射一氧化氮合酶抑制剂L-硝基精氨酸(L-arginine，L-NNA，2.0μg)后，引起睡眠时间增多，觉醒时间减少。2.2大鼠RT内同时微量注射L-NNA(2.0μg)和SNP(0.2μg)后与L-NNA组比较发现SNP逆转了L-NNA的促睡眠作用；RT内同时微量注射L-NNA(2.0μg)和L-Arg(0.5μg)后，与L-NNA(2.0μg)组比较发现L-Arg可以增加觉醒而缩短睡眠，其促觉醒作用未能被NOS的抑制剂L-NNA所逆转。3 RT内阿片肽对大鼠睡眠-觉醒周期的影响3.1大鼠RT内微量注射硫酸吗啡(morphine sulfate，MOR，1.0μg)后与生理盐水组对比，睡眠时间减少而觉醒时间增加； RT内微量注射阿片肽受体拮抗剂盐酸纳洛酮(naloxone hydrochloride，NAL，1.0μg)后与生理盐水组比较，睡眠时间增加而觉醒时间减少。3.2大鼠RT内同时微量注射MOR(1.0μg)和NAL(1.0μg)后，与生理盐水组对比，原有的MOR促觉醒效果和NAL的促睡眠效果都没有表现。4 RT内环一磷酸腺苷信使对大鼠睡眠-觉醒周期的影响大鼠RT内微量注射cAMP(1.0μg)后与NS(1.0μg)组比较，睡眠时间增多而觉醒时间减少；RT内微量注射亚甲蓝(methylene blue，MB，1.0μg)后，与NS组比较，睡眠时间增多而觉醒时间减少。5中缝背核投射到丘脑网状核的5-羟色胺能神经纤维对大鼠睡眠-觉醒周期的影响5.1大鼠DRN内微量注射L-Glu(0.2μg)，同时在双侧RT内微量注射NS (1.0μg)后，与对照组(DRN和双侧RT注射NS， 0.2μg)比较，睡眠时间减少，觉醒时间增多；大鼠DRN内微量注射L-Glu(0.2μg)，同时在双侧RT内微量注射二甲基麦角新碱(methysergide， MS， 1.0μg )后，与对照组(DRN注射L-Glu 0.2μg，双侧RT注射NS 1.0μg)比较，睡眠时间增多，觉醒时间减少。5.2大鼠DRN内微量注射对氯苯丙氨酸(p-chlorophenylalanine，PCPA，10μg)，同时在双侧RT内微量注射NS (1.0μg)后，与对照组(DRN和双侧RT注射NS， 1.0μg)比较，睡眠时间增多，觉醒时间减少；大鼠DRN内微量注射PCPA(10μg)，产生睡眠增多效应后，在双侧RT内微量注射5-羟色胺酸(5-hydroxytryptaphan ， 5-HTP， 1.0μg )后，与对照组(DRN注射PCPA 10μg，双侧RT注射NS 1.0μg)比较，睡眠时间减少，觉醒时间增多。

I am accused of being overreligious," she said in her quiet, frank manner,"but that does not prevent me thinking the children very cruel who obstinately commit such suicide.""

客人们在卡罗利娜·埃凯家里，举止就文雅一些，因为卡罗利娜的母亲治家很严厉。

Designed by French fashion house Herm è s, this elegant uniform was manufactured in our home, Hong Kong, and was the first without a hat.

由著名品牌 Herm è s 设计，这件高贵的制服是香港本土制造，是我们第一套不配帽子的制服。