Studies on analgesic oligopeptides. VI. Further studies of synthesis and biological properties of tripeptide alkylamides, Tyr-D-Arg-Phe-X

Nine analogs based on a structure of Tyr-D-Arg-Phe-X (X = alkylamides or alkylhydrazide containing electron-withdrawing atoms or groups) were newly synthesized and their biological properties were examined by the opioid receptor binding properties of mu-, delta- and kappa-receptors, guinea-pig ileum (GPI) assay and analgesic activity in the tail pinch test after subcutaneous administration in mice. Analogs with X = NHCF2CF3, Sar-ol, or NH(CH2)2CN showed potent activities in the GPI and analgesic assays and high affinity for mu-receptor. An analog with X = taurinamide was found to possess 4-fold higher mu-receptor selectivity than that of [D-Ala2, MePhe4, Gly-ol5]enkephalin (DAGO). The receptor binding properties of previously reported analogs [Chem. Pharm. Bull., 33, 1528 (1985); ibid., 33, 4865 (1985); ibid., 36, 4834 (1988)] were also examined for overall discussion of the structure-activity relationships of this series of tripeptide amides.     

Geometries and rotational barriers of alkylamides and lithium alkylamides.

The barriers to rotation of methylamide, ethylamide and the corresponding lithium amides have been computed at the $\text{ab}$$\text{initio}$ 4-31G level. The barriers to rotation about the CN bond are higher for amides than for amines, but are lowered by coordination with Li⁺.     

Studies on analgesic oligopeptides. VII. Solid phase synthesis and biological properties of Tyr-D-Arg-Phe-beta Ala-NH2 and its fluorinated aromatic amino acid derivatives.

Tyr-D-Arg-Phe-beta Ala-NH2 (I) and its six fluorinated analogs were synthesized. Their opioid receptor binding properties were examined in vitro and their analgesic activity in vivo using the mouse writhing test. It was found that I was one of the most selective and potent mu-receptor agonists reported to date. [Tyr(2F)1](VI) and [Tyr(3F)1](V) derivatives of I showed similar biological properties to those of I. Since these peptides resist enzymatic degradation, it is expected that they are excellent reagents for the studies of function of mu-receptor-mediated biological properties in vivo and in vitro.     

酶促合成肽的研究I.亮-脑啡肽色氨酸类似物的酶促合成

在先后以α-胰凝乳蛋白酶和和木瓜酶作催化剂的作用下,从C端的LeuNH2的氨基开始,逐个与N保护的氨基酸或其衍射生物缩合,合成了亮-脑啡肽色氨酸类似物-TyrGlyGly Trp LeuNH2.对酶的专一性、有机溶剂的选择和合成条件等进行了研究,在Z-TyrOMe和GlyGlyTrp LeuNH2的缩合反应中,比较了相转移法和均相法。上述两种酶的酶促接肽的供体以N-酰基氨基酸酯为好,比相相应的游离酸反应速度快,副反应少,如用嗜热菌蛋白酶,则以N-酰基氨基酸为好,酶促合成与从有机合成所得的产物相同。初步的体外实验表明合成的TyrGlyGlyTrpLeuNH2和天然的亮-脑啡肽对豚鼠回肠的收缩显示相同程度的鸦片样的抑制作用。     

4-Hydroxy-2-quinolones. 180*. Synthesis,chemical reactions,and analgesic activity of 1-allyl-4-hydroxy-6,7-dimethoxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acid alkylamides

A targeted synthesis was carried out of a series of 1-allyl-4-hydroxy-6,7-dimethoxy-2-oxo-1,2-di-hydroquinoline-3-carboxylic acid alkylamides which show interest for biological study as potential analgesics. It was found that, in the presence of one equivalent of bromine, the compounds indicated undergo halocyclization to the corresponding 2-bromomethyl-7,8-dimethoxy-5-oxo-1,2-dihydro-5H-oxa-zolo[3,2-a]quinoline-4-carboxylic acid alkylamides. However, with an excess of bromine the reaction occurs somewhat differently and concludes with the formation of complexes of bromine with 4-alkyl-carbamoyl-2-bromomethyl-5-hydroxy-7,8-dimethoxy-1,2-dihydrooxazolo[3,2-a]quinolinium ditri- bromides. According to the results of pharmacological screening there are found compounds within the substances discovered with high analgesic activity.     

Studies on Agarofurans V. Studies on the Reductive Ring-Opening of 3,4-Epoxide of Agarofurans

The nature of reductive ring-opening of epoxide has been widely studied. But epoxides of agarofurans with rigid skeleton have their own specificity. Agarofurans have been found to be active on the nervous system in our institute. Reduction of epoxides may afford different types of agarofurans. This prompted us to investigate the reaction.Epoxides 1, 2, 3 were prepared by oxidation of their corresponding olefins1. Generally, the nature of the reduction of epoxides with LAH depends on the ster…     

CXN天然沸石的研究 V. 结构超稳化

以离子交换结合控制焙烧的方法分别制得结构超稳化高硅H-STI-I和H-STI-II沸石. EDX, ²⁹Si MAS NMR, ²⁷Al MAS NMR, FT-IR等表征证明, 其骨架硅铝原子比分别为4.43和10.62. 分段程序升温焙烧后的沸石样品经粉末XRD表征表明, 其结构热稳定性达到1000 ℃以上. 结构稳定化沸石呈现反映微孔特性的I型吸附等温线, 吸附孔道完美、开放. 经历过酸处理的H-STI-II沸石, 结构缺陷增多, 其热稳定性、比表面积及孔容积略低于H-STI-I.     

Studies in qualitative inorganic analysis. V

Summary The interference of borate ion in the group separation of inorganic cations has been examined. Contrary to statements often made in text books, alkaline earth borates do not precipitate in Group III because they are soluble in the ammonium chloride present; Group IV metals [Zn, Co], which form more insoluble borates co-precipitate extensively in Group III when borate is present. It is essential, therefore, to remove most of the borate before precipitating Group III metals. A convenient-method for this removal is described.

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Zusammenfassung Die störende Wirkung von Boration bei der Gruppentrennung anorganischer Kationen wurde untersucht. Im Gegensatz zu Feststellungen vieler Lehrbücher fallen Erdalkaliborate nicht in der 3. Gruppe aus, da sie in Ammoniumchlorid löslich sind. Metalle der 4. Gruppe (Zn, Co), die schwerer lösliche Borate bilden, fallen bei Gegenwart von Borat weitgehend in der 3. Gruppe aus. Es ist daher wichtig, Borat vor der Fällung der 3. Gruppe größtenteils zu entfernen. Eine dazu geeignete Methode wird beschrieben.

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Résumé L'effet perturbateur de l'ion borate dans la séparation par groupes des cations minéraux a été étudié. Contrairement à ce qu'on peut lire souvent dans les livres d'analyse les borates alcalino-terreux ne précipitent pas dans le groupe III car ils sont solubles dans le chlorure d'ammonium qui est présent; les métaux du groupe IV (Zn, Co), qui donnent lieu à formation de borates plus insolubles, coprécipitent abondamment avec le groupe III en présence de borate. En conséquence, il est nécessaire d'éliminer la plus grande partie du borate avant de précipiter les métaux du groupe III. Les auteurs décrivent une méthode commode permettant de procéder à cette élimination.

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Part IV: Mikrochim. Acta [Wien] 1957, 137.     

亚磺化脱卤研究 V. Rcel~3型化合物的亚磺化脱卤反应

本文报道RCCl3型化合物的亚磺化脱卤反应,在温和条件下,四氯化碳及1,1,1-三氯多氟烷烃RCCl3(R=Cl, F, CF3, Cl(CF2)n, n=2,4,6,8)与连二亚硫酸钠反应,得到亚磺化脱氯产物RCCl2SO2Na,产率最高达85%以上,反应在水-乙腈或水-乙醇溶剂中以及碳酸氢钠或碳酸钠存在下进行,反应的最佳温度为25℃左右,提高反应温度,则脱氯氢化成为主要反应, 三氯溴甲烷和三氯碘甲烷的亚磺化反应分别生成脱溴及脱碘产物,三氯甲基亚磺酸钠(CCl2SO2Na),产率80%左右. RCCl3型化合物的亚磺化脱卤反应,提供了合成三氯甲基亚磺酸、磺酸及其衍生物的一种新方法,并首次应用于合成α,α二氯多氟烷基亚磺酸、磺酸等类化合物。