康氏霉素C的结构测定

新抗生素康氏霉素Ｃ已从Ｎｏｃａｒｄｉａ ｍｅｄｉｔｅｒｒａｎｅｉ ｖａｒ．ｋａｎｇｌｅｎｓｉｓ １７４７－６４的发酵液中分离出来。它对革兰氏阳性菌有弱抗菌活性，但具有很强的免疫抑制作用。康氏霉素Ｃ具有苯骈［ａ］蒽的碳架，本文根据光谱分析和单晶Ｘ－衍射分析来阐明康氏霉素Ｃ的结构，确定为：［４ａＲ，６ａＲ，１２ａＲ，１２ｂＳ］ｏｒ［４ａＳ，６ａＳ，１２ａＳ，１２ｂＲ］－４ａ，５，６，６ａ，１２ａ，１２     

新免疫抑制剂─—康乐霉素C的发酵、分离、理化性质和生物学性质

从我所提供的Ｎｏｃａｒｄｉａｍｅｄｉｔｅｒｒａｎｅｉｖａｒ．ｋａｎｇｌｅｎｓｉｓ１７６７－６４已分离出了３种确定了经构的新抗生素，即康乐霉素Ａ［１］、康乐霉素Ｃ［２］和３１－ｈｏｍｏｒｉｆａｍｙｃｉｎＷ［３］。由于康乐霉素Ｃ具有很强的免疫抑制作用，在体外其活性如环孢菌素Ａ，具有很好的抗肿瘤活性。本文报道康乐霉素Ｃ的发酵、分离、理化性质和生物学性质。     

得自小根蒜及薤中的几种含氮化合物

从中药薤白的主要基源植物小根蒜（ＡｌｌｉｕｍｍａｃｒｏｓｔｅｍｏｎＢｕｎｇｅ）鳞茎中首次分得５种化合物。它们是腺苷（Ａｄｅｎｏｓｉｎｅ，１）、胸苷（Ｔｈｙｍｉｄｉｎｅ，２）、２，３，４，９－四氢－１－甲基－１Ｈ－吡啶骈［３，４－ｂ］吲哚－３－羧酸（２，３，４，９－ｔｅｔｒａｈｙｄｒｏ－１－ｍｅｔｈｙｌ－１Ｈ－ｐｙｒｉｄｏ［３，４－ｂ］ｉｎｄｏｌｅ－３－ｃａｒｂｏｘｙｌｉｃａｃｉｄ，３）、２，３，４，９－四氢－１Ｈ－吡啶骈［３，４－ｂ］吲哚－３－羧酸（２，３，４，９－ｔｅｔｒａｈｙｄｒｏ－１Ｈ－ｐｙｒｉｄｏ［３，４－ｂ］ｉｎｄｏｌｅ－３－ｃａｒｂｏｘｙｌｉｃａｃｉｄ，４）和丁香甙（Ｓｙｒｉｎｇｉｎ，５）．从另一种基源植物薤（Ａ．ｃｈｉｎｅｎｓｅＧ．Ｄｏｎ）鳞茎中分得腺苷（１）、色氨酸（Ｔｒｙｐｔｏｐｈａｎ，６）和化合物（４）．     

3－芳基丙酸的制备

３－芳基丙酸的制备Ｔｏｔｈ６等［ＳｙｎＣｏｍｍｕｎ，１９９５；２５：８０６７］芳香醛、２，２－二甲基１，３－二烷－４，６－二酮（Ｍｅｌ－ｄｒｕｍ＇ｓａｃｉｄ，ＪＡｍＣｈｅｍＳｏｃ１９４８，７０：３４２６）和三乙胺甲酸盐在２０～５０℃反应，可得５－芳甲...     

早开堇菜的有效成分(英文)

首次报道了自堇菜科植物早开堇菜（ＶｉｏｌａｐｒｉｏｎａｎｔｈａＢｇｅ．）全草中分离到三个香豆素类化合物。根据理化性质与光谱数据（ＩＲ．ＭＳ．１ＨＮＭＲ．１３ＣＮＭＲ．２ＤＮＭＲ）推定，化合物Ⅲ的结构为６－羟基，７－［（６－Ｏ－乙酰基－β－Ｄ－葡萄糖基）－Ｏ－］－香豆素［６－ｈｙｄｒｏｘｙ，７－［（６’－Ｏ－ａｃｅｔｙｌ－β－Ｄ－ｇｌｕｃｏｐｙｒａｎｏｓｙｌ）－ｏｘｙ－］－ｃｏｕｍａｒｉｎ］是新化合物，命名为早开堇菜甙（ｐｒｉｏｎａｎｔｈｏｓｉｄｅ）。化合物Ⅰ、Ⅱ分别为已知化合物七叶内酯（ｅｓｃｕｌｅｔｉｎ）和菊艺甙（ｃｉｃｈｏｒｉｉｎ）。     

青蒿素类 抗疟药artemotil

１商品名 Ａｒｔｅｃｅｆ２化学名 （３Ｒ,５ａＳ,６Ｒ,８ａＳ,ｇＲ,１０Ｓ,１２Ｒ,１２ａＲ）－十氢－１０－乙氧基－３,６,９－三甲基－３,１２－环氧－１２Ｈ－吡喃并［４,３－ｊ］－１,２－苯并二氧杂草３开发与上市厂商 （荷兰）Ｂｒｏｃａｃｅｆ公司研制,２０００年５月首次上市。４适应证 １６岁以下青少年严重恶性疟原虫感染性疟疾的治疗。５药理 本品是从中国多年生草药菊科黄花蒿中分离出来的青蒿素的半合成衍生物,为ＤＮＡ合成抑制剂。 本品是抗原虫感染药物,可杀灭血液中的恶性疟原虫疟疾裂殖体。本品可在血液早…     

新苯骈蒽醌类抗生素康乐霉素M的分离和结构测定

从Ｎｏｃａｒｄｉａｍｅｄｉｔｅｒｒａｎｅｉｖａｒ．ｋａｎｇｌｅｎｓｉｓ１７４７－６４的发酵液中分离到１个新的苯骈蒽醌类抗生素康乐霉素Ｍ。它对革兰氏阳性菌有一定的抑制作用。基于质谱和核磁共振氢谱分析，以及与已知苯骈蒽醌类抗生素的比较，阐明其结构为１，８－ｄｉｈｙｄｒｏｘｙ－３－ｈｙｄｒｏｘｙｍｅｔｈｙｌ－Ｂｅｎｚ［ａ］ａｎｔｈｒａｃｅｎｅ－７，１２－ｄｉｏｎｅ。     

新的高强度高选择性阿片μ受体激动剂［~11C］－羟甲芬太尼的合成

羟甲芬太尼（Ｉ）是一个新的高强度高选择性阿片μ受体激动剂。本文用ｃｉｓ－Ａ－Ｎ－［１－（２－羟基－２－苯乙基）－３－甲基－４－哌啶基］－苯胺（ＩＩ）或ｃｉｓ－Ｎ－［１－（苯甲酰甲基）－３－甲基－４－哌啶基］－苯胺（ＩＩＩ）作为前体合成了［１１Ｃ］－羟甲芬太尼，以便用正电子发射断层扫描（ＰＥＴ）来观察μ受体。通过水解ｃｉｓ－Ａ－羟甲芬太尼（Ｉ）和ｃｉｓ－Ｎ－［１－（苯甲酰甲基）－３－甲基－４－哌啶］－Ｎ－苯基丙酰胺（ｃｉｓ－ＩＶ）的４－Ｎ－丙酰基分别获得ＩＩ和ＩＩＩ。溴乙烷的格氏试剂与回旋加速器产生的［１１Ｃ］－二氧化碳反应后继而直接加入邻苯二甲酸二酰氯和２，６－二叔丁基吡啶生成同位素标记中间体［１１Ｃ］－丙酰氯。［１１Ｃ］－丙酰氯与ＯＨ－前体（ＩＩ）反应后再经ＨＰＬＣ分离纯化直接得［１１Ｃ］－羟甲芬太尼；［１１Ｃ］－丙酰氯与酮－前体（ＩＩＩ）反应后，再用硼氢化钠甲醇溶液处理，然后进行ＨＰＬＣ分离纯化得［１１Ｃ］－羟甲芬太尼。两种方法均可获得ｌｌ．１～１４．８ＧＢｑ／μｍｏｌ的特异性放射化学纯［１１Ｃ］－羟甲芬太尼。总共耗时为４０～５０ｍｉｎ（ＥＯＢ）。     

利哌利酮

利哌利酮（Ｒｉｓｐｅｒｉｄｏｎｅ）３－［２－［４－（６－氟－１，２－苯并异唑－３－基）－１－哌啶基］乙基］－６，７，８，９－四氢－２－甲基－４Ｈ－吡啶并［１，２－ａ］嘧啶－４－酮Ｃ２２Ｈ２７Ｎ４Ｏ２Ｆ（３９５．５）ｍｐ１７０．０℃抗精神病药，对急、慢...     

HEK293细胞—— 一种研究受体Ca~(2+)调控功能的理想模型

目的了解ＨＥＫ２９３细胞Ｃａ２＋代谢的生物学特性。方法用Ｆｕｒａ－２荧光探针双波长测定细胞胞浆游离Ｃａ２＋浓度（［Ｃａ２＋］ｉ）方法，观察多种能改变细胞内Ｃａ２＋代谢的药物对天然的和转染了α１Ｂ肾上腺素受体ｃＤＮＡ的ＨＥＫ２９３细胞［Ｃａ２＋］ｉ的影响。结果在含１．５ｍｍｏｌＬ－１ＣａＣｌ２的缓冲液中，ＫＣｌ５０ｍｍｏｌＬ－１和ＢａｙＫ８６４４１０μｍｏｌＬ－１不影响ＨＥＫ２９３细胞的［Ｃａ２＋］ｉ；ｃｙｃｌｏｐｉａｚｏｎｉｃａｃｉｄ（ＣＰＡ０．０１，０．１，１０μｍｏｌＬ－１）能浓度依赖性地引起ＨＥＫ２９３细胞的［Ｃａ２＋］ｉ呈双相升高，其中的Ｃａ２＋内流相不受ｎｉｆｅｄｉｐｉｎｅ（１０μｍｏｌＬ－１）的影响；但可被１ｍｍｏｌＬ－１ＮｉＳＯ４完全抑制。在无Ｃａ２＋的缓冲液中，咖啡因２０ｍｍｏｌＬ－１和ｒｙａｎｏｄｉｎｅ１μｍｏｌＬ－１均不影响ＨＥＫ２９３细胞的［Ｃａ２＋］ｉ。先用ＣＰＡ（３０μｍｏｌＬ－１）耗竭ＨＥＫα１Ｂ细胞内Ｃａ２＋贮存池后，肾上腺素１０μｍｏｌＬ－１能进一步升高［Ｃａ２＋］ｉ。在有Ｃａ２＋或无Ｃａ２＋的缓冲液中，肾上腺素均可引起ＨＥＫα１Ｂ细胞［Ｃａ２＋］ｉ升高。结论ＨＥＫ２９３细胞?     

Sesquiterpenes from the aerial parts of Artemisia vestita Wall.

A chemical investigation of the aerial parts of Artemisia vestita Wall. led to the isolation of 12 known sesquiterpenes, including 2 furan-containing sesquiterpenoids and 10 eudesmane sesquiterpene lactones. Their structures were identified as negunfurol (1), schensianol A (2), artemine (3), erivanin (4), 1,5-diepi-artemin (5), acetylartemin (6), naphtho[1,2-b]furan-2(3H)-one, 6-(acetyloxy)decahydro-9a-hydroxy-3,5a-dimethyl-9-methylene-(3S,3aS,5aS,6S,9aS,9bS) (7), naphtho[1,2-b]furan-2(3H)-one, 6-(acetyloxy)-3a,4,5,5a,6,7,8,9b-octahydro-8-hydroxy-3,5a,9-trimethyl- (3S,3aS,5aR,6S,8S,9bS) (8), isoerivanin (9), barrelierin (10), (11S)-1-oxoeudesm-4(14)-eno-13,6α-lactone (11), 1-epi-dehydroisoeranin (12), respectively. All of these compounds were isolated from Artemisia vestita for the first time, and compounds 1 and 2 were isolated from the genus Artemisia for the first time.     

Axially chiral 1,7-naphthyridine-6-carboxamide derivatives as orally active tachykinin NK(1) receptor antagonists: synthesis, antagonistic activity, and effects on bladder functions.

Cyclic analogues of N-[3,5-bis(trifluoromethyl)benzyl]-7,8-dihydro-N, 7-dimethyl-5-(4-methylphenyl)-8-oxo-1,7-naphthyridine-6-carboxamide (1) having a 6-9-membered ring (6-9) were synthesized and evaluated for NK(1) antagonistic activities. The 8-membered ring compound with a beta-methyl group at the C((9))-position, (aR,9R)-7-[3, 5-bis(trifluoromethyl)benzyl]-8,9,10, 11-tetrahydro-9-methyl-5-(4-methylphenyl)-7H-[1,4]diazocino[2,1-g] [1, 7]naphthyridine-6,13-dione [(aR,9R)-8b], was atropodiastereoselectively synthesized by cyclization of a chiral intermediate, 10g. On the other hand, the 7-membered ring compound with a beta-methyl group at the C((9))-position [(9S)-7b] was obtained as an equilibrium mixture of atropisomers with a ratio of ca. 3:2 in solution at room temperature (measured by NMR in CDCl(3)). Compounds (9S)-7b and (aR,9R)-8b exhibited excellent antagonistic activities both in vitro [IC(50) (inhibition of [(125)I]BH-SP binding in human IM-9 cells) = 0.28 and 0.45 nM, respectively] and in vivo (iv and po). Significantly, the in vitro activity of (aR, 9R)-8b was ca. 750-fold higher than that of its enantiomer (aS, 9S)-8b, ca. 40-fold higher than its atropisomer (aS,9R)-8b, and ca. 20-fold higher than its diastereomer (aR,9S)-8b. The structure-activity relationships in this series, along with the X-ray analysis of (aR,9R)-8b, indicated that the stereochemistry around the -C((6))(=O)-N((7))-CH(2)Ar moiety is important for NK(1) receptor recognition. The NK(1) antagonists showed effects on bladder functions in guinea pigs upon intravenous injection: i.e., the antagonists increased the shutdown time of distension-induced rhythmic bladder contractions and the bladder volume threshold, and the effects on the shutdown time were found to correlate well with the NK(1) antagonistic activities. Compound (aR,9R)-8b has been identified as a potential clinical candidate for the treatment of bladder function disorders.     

Isolation and identification of chemical constituents from Taxus cuspidta Sibe et Zucc

Three compounds were isolated from the extract of Taxus cuspidta Sibe et Zucc with the column chromatography on silica gel and preparative HPLC methods. Their structures were identified according to the physicochemical properties and spectral analysis, and they were identified as (E)-1-methoxy-2-O-(p-coumaroyl)-myo-inositol (1), 2-deacetoxy-7beta, 9a, 10beta-trideacetyltaxinine J (2) and (3aS, 4aR, 6S, 8S, 8aS, 9R, 10R, 10aS)-benz[f]azulene-6, 8, 9, 10 (3H)-terol, 3a, 4, 4a, 5, 6, 7, 8, 8a, 9, 10-decahydro-10a-(1-hydroxyl-1-methylethyl)-1, 8a-dimethyl-5-methylene (3). Among them, compound 1 was a new compound, and compounds 2, 3 were two novel natural products.     

托吡酯的合成工艺改进

本研究发现在托吡酯(1)的合成过程中可生成杂质[(3aS,5aR,8aR,8bS)-2,2,7,7-四甲基四氢-3aH-双[[1,3]二氧戊环]-并[4,5-b:4',5'-d]吡喃-3a-基]甲基[(3aS,5aS,8aR,8bS)-2,2,7,7-四甲基四氢-3aH-双[[1,3]二氧杂戊环]并[4,5-b:4',5'-d]吡喃-3a-基)甲基]氨基磺酸酯(4),其结构经核磁和质谱鉴定确证,证明4是由油状物2,3:4,5-双-O-(1-甲基亚乙基)-β-D-吡喃果糖氯磺酸酯(2)中残余的2,3:4,5-双-O-(1-甲基亚乙基)-β-D-吡喃果糖苷(3)与1反应引起。因此,对2合成工艺进行了改进。将3与磺酰氯在二氯甲烷/甲苯混合溶剂中反应得油状物2,经异丙醚精制首次制得固体2,其中3的含量降至0.05%。将固体2与氨气反应得1,产品无需精制,纯度99.93%,总收率87%(以3计)。该工艺易于除去杂质,所得中间体2为固体,存储取样方便。     

Pyrrole and indole alkaloids from an endophytic Fusarium incarnatum (HKI00504) isolated from the mangrove plant Aegiceras corniculatum

Two new pyrrole alkaloids, N-[4-(2-formyl-5-hydroxymethyl-pyrrol-1-yl)-butyl]-acetamide (1) and N-[5-(2-formyl-5-hydroxymethyl-pyrrol-1-yl)-pentyl]-acetamide (2), and a new indole derivative (3aR,8aR)-3a-acetoxyl-1,2,3,3a,8,8a-hexahydropyrrolo-[2,3-b]indol (3) were isolated, together with ( - )-3a-hydroxyfuroindoline, (3aR,8aS)-1-acetyl-1,3,3a,8,8a-hexahydropyrrolo-[2,3-b]indol-3a-ol, and N-acetyltryptamine A, from an endophytic ascomycetous fungus, Fusarium incarnatum (HKI00504), which was isolated from the mangrove plant Aegiceras corniculatum. The structures of compounds 1-3 were determined on the basis of extensive spectroscopic data analyses.     

Pyrrole and indole alkaloids from an endophytic Fusarium incarnatum (HKI00504) isolated from the mangrove plant Aegiceras corniculatum

Two new pyrrole alkaloids, N-[4-(2-formyl-5-hydroxymethyl-pyrrol-1-yl)-butyl]-acetamide (1) and N-[5-(2-formyl-5-hydroxymethyl-pyrrol-1-yl)-pentyl]-acetamide (2), and a new indole derivative (3aR,8aR)-3a-acetoxyl-1,2,3,3a,8,8a-hexahydropyrrolo-[2,3-b]indol (3) were isolated, together with ( - )-3a-hydroxyfuroindoline, (3aR,8aS)-1-acetyl-1,3,3a,8,8a-hexahydropyrrolo-[2,3-b]indol-3a-ol, and N-acetyltryptamine A, from an endophytic ascomycetous fungus, Fusarium incarnatum (HKI00504), which was isolated from the mangrove plant Aegiceras corniculatum. The structures of compounds 1-3 were determined on the basis of extensive spectroscopic data analyses.     

Bioisosteric modification of salvinorin A, a potent and selective kappa-opioid receptor agonist

Salvinorin A ((2S,4aR,6aR,7R,9S,10aS, 10bR)-2H-naphtho[2,1-c]pyran-7-carboxylic acid, 9-(acetyloxy)-2-(3-furanyl)dodecahydro-6a,10b-dimethyl-4,10-dioxo methyl ester, 1, CAS 83729-01-5) has been shown to bind with high affinity and selectivity to the kappa-opioid receptor (KOR) as an agonist. Bioisosteres of 1 were developed and biologically evaluated in binding and functional assays. The C-2 thioacetate isoster produced comparable activity to 1, but nitrogen substitution had a diminishing effect. Intermediates, which lack a beta-carbonyl at C-2, displayed moderate affinity. The derivatives were tested against all opioid subtypes and were selective towards KOR.     

The alpha(1A)-adrenoceptor subtype mediates contraction in rat femoral resistance arteries.

In this study, alpha(1)-adrenoceptor subtypes were characterised in rat femoral resistance arteries mounted on a small vessel myograph. A-61603 was found to be more potent than noradrenaline and phenylephrine in these arteries. Brimonidine (UK 14304) could not evoke any contractile responses and the sensitivity to noradrenaline and phenylephrine was not affected by (8aR,12aS,13aS)-5,8,8a,9,10,11,12,12a,13a-decahydro-3-methoxy-12-(ethylsulphonyl)-6H-isoquino[2,1-g][1,6]-naphthyridine (RS 79948), ruling out the presence of alpha(2)-adrenoceptors. Prazosin, 5-methyl-urapidil and 2-([2,6-dimethoxyphenoxyethyl]aminomethyl)-1,4-benzodioxane (WB 4101) produced rightward shifts in the sensitivity to noradrenaline, giving pA(2) values of 9.6, 9.4 and 10.4, respectively, in agreement with the presence of alpha(1A)-adrenoceptors. (8-[2-[4-(2-Methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione (BMY 7378; 1 microM) produced a small shift in the sensitivity of noradrenaline giving a pK(B) of 7.2. In the presence of 300 nM 5-methyl-urapidil, sensitivity to noradrenaline was not further shifted by 1 microM BMY 7378. Responses to noradrenaline were unaffected by the alpha(1B)-adrenoceptor alkylating agent chloroethylclonidine (1 microM). These results suggest alpha(1A)-adrenoceptors mediate contractile responses to noradrenaline in rat femoral resistance arteries.     

西沙群岛软珊瑚Lemnalia sp.倍半萜类次级代谢产物研究

目的 对西沙群岛软珊瑚样品Lemnalia sp.进行萜类次级代谢产物的化学结构研究.方法 利用薄层色谱、硅胶柱层析、高效液相色谱和中压制备液相色谱等分离手段对软珊瑚提取物中的化合物进行分离、纯化;运用核磁共振、质谱等现代波谱学方法,通过与报道的数据进行对比,对化合物的化学结构进行鉴定.结果 从西沙群岛软珊瑚Lemna...     

Synthesis of optically active TAN-67, a highly selective delta opioid receptor agonist, and investigation of its pharmacological properties.

We have synthesized the nonpeptidic highly selective delta opioid receptor agonist, (+/-)-TAN-67, (4aS*, 12aR*)-4a-(3-hydroxyphenyl)-2-methyl-1,2,3,4,4a,5,12,12a-octahydropyrido [3,4-b] acridine. In spite of high potent agonist activity for the delta opioid receptor in in vitro assay, (+/-)-TAN-67 afforded no analgesic activity in the mouse warm-plate test. This result led us to separate (+/-)-TAN-67 into optically pure compounds. Each enantiomer of racemic TAN-67 was synthesized from the corresponding optically active 6-oxodecahydroisoquinoline which was obtained by fractional recrystallization of its optically pure di-p-toluoyl tartaric acid salt. In bioassay using mouse vas deferens, (-)-TAN-67 showed full agonist activity (IC50 = 3.65 nM). On the other hand, (+)-TAN-67 showed almost no agonist activity, but interestingly afforded hyperalgesic activity in vivo (i.t. injection).