Fmc，镰刀菌来源的多巴胺1受体抑制剂

应用以中枢神经系统为主的八个体外受体筛选系统,从15株真菌和12株放线菌中筛选出能产生具有与多巴胺1受体竞争性结合活性的镰刀菌Fusarium moniliflore;从其菌体中分离出活性成分Fmc。通过元素分析和质谱,确定其分子式为C10H13O2N。综合紫外光谱、红外光谱、^1H-NMR和^13C-NMR等图谱数据的解析,确定Fmc的结构与镰刀属真菌（Fusarium moniliflore)发酵液分离出来的夫西地酸（fusaric acid)一致,化学命名为：5－正丁基吡啶酸。但关于其作用于中枢神经系统多巴胺1受体的活性未见报道。     

化合物wortmannilactones产生菌F01-195的鉴定及发酵条件研究

对自云南土壤分离得到的真菌F01-195从形态特征、培养特性等方面进行了分类鉴定，认为该菌株属于邬氏黄丝曲霉（Talaromyces wortmannil），该菌可以产生新的22元环macrolactin类大环内酯类化合物wortmannilactones A、B、C、D。此外，对该菌株的发酵条件的研究结果表明只有在固体培养条件下该菌株才能产生wortmannilactones。     

大杯香菇化学成分的分离与鉴定

目的对真菌大杯香菇（Lentinus giganteus Berk）的化学成分进行研究。方法用多种色谱技术对化合物进行分离纯化。并用光谱技术和理化性质鉴定化合物的结构。结果从大杯香菇乙醇提取物中分离得到4个化合物，分别鉴定为ergosterol peroxide（1）、（3β，5α，8α，22E，24R）-5，8-epidioxyergosta-6，9（11），22-tfien-3-ol（2）、stellasterol（3）、glycerol 1-（9Z，12Z—octadecadienoate）-3-nonadecanoate（4）。结论化合物2～4为首次从该属真菌中分离得到，经MTT法进行体外抗肿瘤活性测试，3个化合物对小鼠B16细胞和人肝癌细胞SMMC-7721均无生长抑制活性。     

链霉菌JXJ-402产生的抗生素JXJ-402-1的研究

在筛选微生物来源抗生素的过程中，从500余株链霉菌中发现十余株抗真菌阳性菌株，其中JXJ-402菌株显示出较强的抗稻瘟病菌活性。从该菌株固体发酵粗提取物中分离纯化到化合物JXJ-402-1。经^13C-NMR数据分析，确定其化学结构与文献报道的尼日利亚菌素（nigericin）结构一致。生物学活性研究发现，化合物JXJ-402-1具有抗稻瘟病菌、赤星病菌、白念珠菌、藤黄微球菌和枯草芽孢杆菌等真菌和细菌活性，其中抗稻瘟病菌和赤星病菌活性未见文献报道。     

南海海绵Clathria fasciculate化学成分的研究(Ⅱ)

从中国南海海绵Clathria fasciculate的乙酸乙酯相分离鉴定出4个有机化合物，经GC-MS，FAB，IR，^1HNMR,^13CNMR和COSY等波谱技术确定它们分别是：胆甾-4-烯-3-酮（Ⅰ）；豆甾-4-烯-3-酮（Ⅱ）；（Z）-17-二十四碳烯-1-醇（Ⅲ）和1-（17Z-二十四碳烯基）-甘油醚（Ⅳ），为首次有关该种属海绵化学成分研究系列的第二次报道。     

1-(1H-1,2,4-三唑-1-基)-2-叔丁基-3-[(4-取代苄基)-哌嗪-1-基]-2-丙醇的合成及其抗真菌活性的研究

目的研究具有叔丁基结构的三唑醇类化合物的抗真菌活性以及各种4-（取代苄基）哌嗪侧链的引入对该类化合物抗真菌活性的影响。方法设计合成了13个未见文献报道的目标化合物，所有化合物结构均经^1H-NMR谱确证，部分经过IR、MS确证；选择8种真菌为实验菌株，测定其体外抗真菌活性。结果所有化合物对8种真菌均有一定的抑制作用。其中，Ⅲ7的抑菌活性优于氟康唑。结论引入叔丁基和哌嗪侧链设计的目标化合物都具有抗真菌活性，侧链取代基的电性效应和立体化学特征的改变对该类化合物的抑菌活性有一定的影响。     

1-(1H-1,2,4-三唑-1-基)-(2,4-二氟苯基)-3-(N-异丙基-N-取代氨基)-2-丙醇的合成及抗真菌活性

目的：以氟康唑为先导化合物,设计合成新的三唑醇类化合物,并研究其抗真菌活性。方法：引入异丙基及取代氨基侧链结构,合成一系列目标化合物,所有化合物结构均经MS、^1H—NMR等谱确证;选择8种真菌为实验菌株,测定其体外抗真菌活性。结果：合成了15个目标化合物;所有化合物对所选真菌均表现出了一定的抑菌活性,其中化合物（6c）,（6d）,（6e）,（6f）和（6g）对除薰烟曲霉菌外的7种菌株都表现出了较好的抑菌活性。结论：取代氨基侧链结构的引入对目标化合物的抗菌活性有一定的影响,侧链为取代苄基活性较好,且取代苄基侧链越短,抑菌活性越好。     

一株海南三亚红树林真菌Alternaria alternate次级代谢产物的研究

目的 对1株来源于海南三亚红树林淤泥中的链格孢霉属真菌Alternaria alternate SY5-1-1次级代谢产物进行研究。方法 通过减压硅胶柱层析、Sephadex LH-20凝胶柱层析、反相中压以及半制备HPLC等色谱技术对其次级代谢产物进行分离纯化。通过MS和NMR等波谱方法以及对比文献,确定化合物的结构。结果 从真菌Alternaria alternate SY5-1-1乙酸乙酯提取物中分离得到11个化合物分别为secalonic acid A（1）、altertoxin I（2）、N-[(Z)-2-(4-hydroxyphenyl) ethenyl]-formamide（3）、5-hydroxymethyl-2-furoic acid（4）、dibutyl phthalate（5）、cyclotryprostatin A（6）、dihydrovermistatin（7）、verruculogen TR-2（8）、cyclo-(L-4-OH-Pro-L-Leu)（9）、cyclo-(trans-4-OH-D-Pro-D-Phe)（10）和cyclo-(D-Pro-D-Phe)（11）。结论 化合物secalonic acid A（1）、N-[(Z)-2-(4-hydroxyphenyl) ethenyl]-formamide（3）、5-hydroxymethyl-2-furoic acid（4）、cyclotryprostatin A（6）、dihydrovermistatin（7）、verruculogen TR-2（8）均首次在链格孢霉属真菌中发现。     

1-(1H-1,2,4-三唑-1-基)-(2,4-二氟苯基)-3-[N-环丙基-N-(4-取代苄基)]-2-丙醇的合成及抗真菌活性

目的：以氟康唑为先导化合物,设计合成新的三唑醇类化合物,并研究其抗真菌活性。方法：引入4位羧酸酯取代的苄基侧链结构,合成一系列目标化合物,所有化合物结构均经MS、^1H-NMR等谱确证;选择8种真菌为实验菌株,测定其体外抗真菌活性。结果：合成了15个未见文献报道的目标化合物;所有化合物对所选真菌均表现出了一定的抑菌活性,其中化合物（1）,（2）和（3）对除薰烟曲霉菌外的7种菌都表现出了较好的抑菌活性。结论：4位羧酸酯取代的苄基侧链结构的引入对目标化合物的抗菌活性有一定的影响,侧链越短．抑菌活性越好.     

一株高产抗寄生虫环肽emodepside前体产生菌的鉴定及其次级代谢产物PF1022A的结构分析

目的 抗寄生虫环肽emodepside前体产生菌的鉴定及其次级代谢产物PF1022A结构分析。方法 本实验室通过紫外诱变得到一株高产抗寄生虫环肽emodepside前体的突变株，采用形态观察、生理生化特征鉴定、ITS基因序列对比及系统发育学分析等相结合方法来确定该菌株的分离学地位，以及对该菌株经深层发酵，经LC-MS、1H NMR和13C NMR、DEPT 90和DEPT 135、1H-1H COSY、HMQC、HMBC分析测定来确定产生次级代谢产物X的分子结构。结果与结论 鉴定突变株CBR72-MCB-01呈现出座坚壳属(Rosellinia)菌株的形态学特征；经鉴定代谢产物结构与文献报道的抗寄生虫环肽PF1022A结构一致。     

Effects of (+/-)- (+)- and (-)-metoprolol, (+/-)- (+)- and (-)-pindolol, (+/-)-mepindolol and (+/-)-bopindolol on the rat left atria and portal vein.

1. The effects of (+/-)- (+)- and (-)-metoprolol, (+/-)- (+)- and (-)-pindolol, (+/-)-mepindolol and (+/-)-bopindolol on the beta 1-adrenoceptor mediated responses of the rat left atria and the beta 2-adrenoceptor mediated responses of the rat portal vein to isoprenaline have been determined. 2. Racemic and (-)-metoprolol were selective beta 1-adrenoceptor antagonists. (+)-Metoprolol was devoid of beta-adrenoceptor antagonistic activity. 3. Racemic and (-)-pindolol were potent and (+)-pindolol was a modest beta-adrenoceptor antagonist. 4. (+/-)-Mepindolol and (+/-)-bopindolol were apparently competitive antagonists of the isoprenaline beta 1-adrenoceptor mediated responses of the rat left atria but non-competitive antagonists of the isoprenaline beta 2-adrenoceptor mediated responses of the rat portal vein. 5. It is suggested that (+/-)-mepindolol and (+/-)-bopindolol are slowly dissociating beta-adrenoceptor antagonists and the non-competitive antagonism can only be detected on tissues with modest receptor reserves for maximum responses to isoprenaline.     

Synthesis of (R)-(-)- and (S)-(+)-4-fluorodeprenyl and (R)-(-)- and (S)-(+)-[N-11C-methyl]-4-fluorodeprenyl and positron emission tomography studies in baboon brain

(R)-(-)- and (S)-(+)-alpha-methyl-beta-4-(fluorophenyl)-N-methyl-N- propynylethylamine [R)-(-)- and (S)-(+)-4-fluorodeprenyl) were synthesized via the reaction of 4-fluorobenzaldehyde with nitroethane followed by reduction with lithium aluminum hydride to produce racemic 4-fluoroamphetamine, which was resolved by recrystallization with L- or D-N-acetylleucine to yield (R)-(-)-4-fluoroamphetamine or (S)-(+)-4-fluoroamphetamine in greater than 96% enantiomeric excesses and in yields of 42 and 39%, respectively. Alkylation with propargyl bromide gave (R)-(-)- or (S)-(+)-4-fluoronordeprenyl which was reductively methylated (Borch conditions) to produce (R)-(-)- or (S)-(+)-4-fluorodeprenyl. Alkylation of (R)-(-)- or (S)-(+)-4-fluoronordeprenyl with carbon-11 labeled methyl iodide gave (R)-(-)- or (S)-(+)-[N-11C-methyl]-4-fluorodeprenyl in a radiochemical yield of 30-40%. Comparative PET studies of the two labeled enantiomers in baboons showed a significantly lower retention of radioactivity in the striatum for the (S)-(+) enantiomer relative to the (R)-(-) enantiomer.     

Synthesis and dopamine agonist and antagonist effects of (R)-(-)- and (S)-(+)-11-hydroxy-N-n-propylnoraporphine

The R-(-) and S-(+) enantiomers of 11-hydroxy-N-n-propylnoraporphine, (R)-3 and (S)-3, were synthesized in six steps from 1-(3-methoxy-2-nitrobenzyl)isoquinoline. Neuropharmacological evaluation of the R and S isomers (by affinity to dopamine receptor sites in rat brain tissues, induction of stereotyped behavior, and interaction with motor arousal induced by (R)-apomorphine in the rat) indicated that, similar to the 10,11-dihydroxy congener 2, both enantiomers can bind to dopamine receptors but that only (R)-3 activates them, whereas (S)-3 shows activity as a dopaminergic antagonist.     

Pharmacokinetics of (+)-, (-)- and (+/-)-verapamil after intravenous administration

The pharmacokinetics of (+)-, (-)-, and (+/-)-verapamil were studied in five healthy volunteers following i.v. administration of the drugs. Pronounced differences of the various pharmacokinetic parameters were observed between the (-)- and (+)-isomers. The values for CL, V, Vz, and Vss of the (-)-isomer were substantially higher as compared to the (+)-isomer, whereas terminal t 1/ 2Z was nearly identical for both isomers. No dose dependency of the pharmacokinetics could be observed in two subjects who received 5, 7.5 and 10 mg of (-)- and 5, 25 and 50 mg of (+)-verapamil. Protein binding for the two isomers was also different. The fu of (-)- (0.11) was almost twice as much as that of (+)-verapamil (0.064). Pharmacokinetic parameters of (+/-)-verapamil, which was administered to three subjects who had received (+)- and (-)-verapamil, were very similar to the averaged values of the isomers given separately. Due to the higher CL of (-)-verapamil the extraction ratio of the (-)-isomer is substantially higher. Thus, it can be anticipated that following oral administration of racemic verapamil bioavailability of (-)-verapamil will be substantially less. Since the (-)-isomer is more potent than the (+)-isomer, the present findings could explain the reported differences in the concentration-effect relationship after i.v. and oral administration of racemic verapamil.     

Antinociceptive effects of (+/-)-, (+)- and (-)-nefopam in mice

The antinociceptive activity of (+/-)-, (+)- and (-)-nefopam in mice has been examined using the hot-plate, formalin and tail-flick tests. Nefopam was administered by the intraperitoneal, intracerebroventricular (i.c.v.) and intrathecal (i.th.) routes. Intraperitoneal injection of (+/-)-nefopam (10-20 mg kg-1) had powerful analgesic effects in the hot-plate and formalin tests. In the tail-flick test it produced a weak, but significant elevation of the response latencies. In spinalized animals, however, the effect was abolished, indicating that nefopam prolonged the tail-flick latencies by activation of descending pain-modulating pathways. (+/-)-Nefopam (5-20 micrograms) elicited analgesia in the hot-plate test after i.c.v. or i.th. injection. These findings suggest that nefopam has both a spinal and a supraspinal site of action. (+)-Nefopam was significantly more potent than (-)-nefopam after both systemic and central administration.     

头孢曲松钠中残留的三嗪环的定性定量研究

目的:对头孢曲松钠中的三嗪环进行定性定量测定,可以控制其残留总量,减少过敏反应的发生,促进工艺改进。方法:本文采用质谱(MS)、红外吸收光谱(IR)与核磁共振谱(NMR),对获得的三嗪环参照品进行结构确认,然后用高效液相色谱法(HPLC)对其在头孢曲松钠中的残留进行定量测定。结果:表明所获得的三嗪环参照品纯度很高,能够对头孢曲松钠作定性定量分析。结论:头孢曲松钠中三嗪环的残留在安全限度之中。     

Synthesis and pharmacological properties of some 2-(3-aminopropionyl)- and 2-(3-aminopropyl)-1-(3-pyridyl)-1,2,3,4-tetrahydro-beta-carbolines

Five derivatives of 2-(3-aminopropionyl)-1-(3-pyridyl)-1,2,3,4-tetrahydro-beta-carboline (2a-e) were obtained, which yielded, as a result of reduction with LiAlH4, five respective 2-aminopropyl-derivatives (3a-e). Pharmacological studies revealed that phenylpiperazine-derivatives 2d, 2e, 3d and 3e have sedative and analgesic properties. All compounds are devoided of neuroleptic, antidepressant, anxiolytic and antiparkinsonic activity.