巯基丙氨酸

Then Doripenem came into the market in the July ,2005. We studied the synthesis of Doripemen.Firstly, we synthesized the chemical 2 from the starting material------o-hydroxylphenylacylamine through Reformastky reaction, alkylation, Diekmann reaction, enolization, esterification and etc. Secondly, we synthesized the chemical 3 from L — hydroxylproline through the protection of carboxyl, amidogen and hydroxyl group, reduction by NaBr, SN_2 substitution and Mitsumobu reaction.

我们以水杨酰胺为起始原料，经Reformatsky反应、烷基化、Diekmann环合、烯醇化、酯化等反应合成双环母核2；再从L-羟基脯氨酸出发，经酯化保护羧基、保护氨基、保护羟基、硼氢化还原酯得醇、Sn2取代和Mitsumobu反应等合成巯基侧链3；最后由化合物3经脱保护、水解得硫醇，和化合物2在二异丙基乙基胺的作用下缩合，最后Pd／C催化脱保护，历经16步反应最终得到产物多尼培南。

E. 3-allyloxyisothiazole and N-allylisothiazolone, were synthesized with 3-mercaptopropionate as the starting material through ammonolysis, cyclization and allylation reactions.

以3-巯基丙酸甲酯为原料，经氨解、关环、烯丙基化合成了2种含有不饱和侧链的异噻唑类化合物，分别为3-烯丙氧基异噻唑和N-烯丙基异噻唑啉酮。

Ophenyl phenol,ophenyl phenol sodium salt tetrahydrate,7ADCA,2ethyl phenyl hydrazine hydrochloride,2,3dihydrofuran,7ethyl3(2hydroxy ethyl)indole,methyl ester of etodolac; 1,8diethyl1,3,4,9tetrahydropyrano[3.4b] indole1acetic acid methyl ester,5chloro2methoxy benzoic acid,4(2aminoethyl)benzene sulfonamide,5cyano phthalide,phthalhydrazide,9thioxanthenone,n[(1,4benzodioxane2yl)carboxyl]piperazine HCL,2chloro4amino6,7dimethoxyquinazoline,2chloro benzimidazole,1(4fluorobenzyl)2chlorobenzimidazole,2methylthio4pyrimidone,5amino4imidazole carboxamide HCL,6chloro2hexanone,11oxo6.11hydrodibenzothiepin,6,11dihydrodibenzooxepin11one,10,11dihydrodibenzocyclohepten5one;dibenzosuberone,dibenzo cyclohepten5one;dibenzosuberenone,3,5dihydroxy benzoic acid,3,5dihydroxy benzyl alcohol,2mercapto benzimidazole,3,4dihydroxy benzaldehyde,3,4dihydroxy benzonitrile,2amino5chloro benzonitrile,2(4chlorophenoxy)ethyl chloride,2(4chloro phenoxy)tert,butane,ditrimethylol propane;DTMP,2,2bis(4hydroxyphenyl)butane; bisphenol B,1,1'bis(4hydroxyphenyl)cyclohexane;bisphenol Z,tetrabromobisphenolS,3,5ditertbutyl salicylic acid,3,4,5trihydroxy benzoic acid stearyl ester,1,2,4trimethoxybenzene.

华业公司产品：邻苯基苯酚，邻苯基苯酚钠盐，7氨基3去乙酰氧基头孢烷酸，邻乙基苯肼盐酸盐，2，3二氢呋喃，7乙基色氨醇，依托度酸甲酯，5氯2甲氧基苯甲酸，4(2氨乙基)苯磺酰胺，5氰基苯酞，双酮酞嗪，9噻吨酮，N〔(1，4苯并二恶烷2基)羰基〕哌嗪盐酸盐，2氯4氨基6，7一二甲氧基喹唑啉，2氯苯并咪唑，1(4氟苄基)2氯苯并咪唑，2甲硫基4嘧啶酮，5氨基咪唑4 甲酰胺盐酸盐，6氯2已酮，11氧6.11二氢苯并〔b.c〕虑平，11氧代6，11二氢二苯并氧杂卓，10，11二氢二苯并环庚烯5酮，二苯并环庚烯5酮，3，5二羟基苯甲酸，3，5二羟基苯甲醇，2巯基苯并咪唑，3，4二羟基苯甲醛，3，4二羟基苯腈，2氨基5氯苯腈，2(4氯苯氧基)1氯乙烷，2(4氯苯氧基)叔丁烷，双丙烷，2，2二(4羟基苯基)丁烷；双酚B，1，1'双(4羟基苯基)环己烷；双酚Z，2[3，5二溴4(2，3二溴丙氧基)]苯砜，3，5二叔丁基水杨酸，3，4，5三羟基苯甲酸十八烷基脂，1，2，4三甲基氧基苯。

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。

The simple and fast determination method presented is based on initial chelation of Sn4+, Cu2+, Pb2+ and other metal ions with EDTA and its subsequent decomposition with trihydroxybenzoic acid, mercaptosuccinic acid and dithiocarbamic propanoic acid.

本文提出的简易、快速测定方法是用EDTA螯合锡、铜、铅和其它金属离子，然后分别用三羟基甲酸、巯基丁二酸和氨荒丙酸解蔽。

The MICs of isoniazid, L-canavanine, L-azetidine-2-carboxylic acid and mercaptopurine for D. salina in liquid medium were over 200mg·L-1, while the MIC of ρ-Fluorophenylalanine was only 180mg·L-1.D.

液体培养中刀豆氨酸、异烟肼、玲蓝氨酸和6-巯基嘌呤对盐藻的最低抑制浓度均超过200mg·L-1，而ρ-氟苯丙氨酸最低抑制浓度则为180mg·L-1。

Plunder melds and run with this jewel!

掠夺melds和运行与此宝石！

My dream is to be a crazy growing tree and extend at the edge between the city and the forest.

此刻，也许正是在通往天国的路上，我体验着这白色的晕旋。