Structure-activity relationships of cyclic acetylcholine analogues of the piperidinol and thiacyclohexanol series

Summary The hydrochlorides and methiodides of 1-methyl-3- and 4-acetoxypiperidine and their sulphonium analogues are cholinergic agonists. They are substrates for acetylcholinesterase. The sulphonium compounds have a 78(-524)-fold higher activity than its nitrogen analogues.We thank the German Research Association for support of this work, and MissChristiane Roth for her valuable assistance in carrying out the investigations.     

Peptolide

Summary A summary is given on the occurrence, isolation, biological activity and structural details of peptolides, a special group of the heteromere peptides. The structure is generally evaluated by identification of the amino- and hydroxyacids, isolated after total acid hydrolysis, and by isolation of the hydroxyacylaminoacids to be found after partial alkaline hydrolysis.In addition, the methods known for the synthesis of these compounds are described. For the building up of the ester bond between amino- and hydroxyacid, the methods via benzenesulfonyl chloride, mixed anhydrides, and carbonyldiimidazol are well to the fore. Activated esters, the azide method or, in the case of O-protected hydroxyacid, the acid chloride method are described for the building up of the amide bond between hydroxy- and aminoacid. The further synthesis of peptolides is chiefly ensued originating from the aminoacyl-hydroxyacid type according to the usual methods of the peptide synthesis. The possible combination of protecting groups for the blocking of the amino and carboxyl function is discussed. The synthesis of higher compounds is explained with the assistance of two reaction schemes. A cyclization and hence the synthesis of the natural material can be done according to the acid chloride or mixed anhydride method.

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Hauptlaboratorium derSchering AG, Berlin-West (Dentschland). Für Anregungen, wertvolle Diskussionen und das rege Interesse an unserer Arbeit sind wir Herrn Dr.H. Gibian zu Dank verpflichtet.     

Becquerel and the choice of uranium compounds

Conclusion The common assumption that Becquerel had no special reason to study uranium compounds in his search for substances emitting penetrating radiation cannot explain (a) Becquerel's own accounts, which refer to his choice as due to the peculiar harmonic series of bands; (b) Becquerel's systematic test of all uranium compounds (and metallic uranium), in contrast to his neglect of other substances; and (c) Becquerel's belief in invisible phosphorescence as an explanation of the radiation emitted by uranium compounds, even after his discovery that non-luminescent and metallic uranium also emit penetrating radiation.By comparing Becquerel's older studies of uranium to his radioactivity research, this paper has presented a reconstruction that can explain all of these points above. According to the historical evidence presented here, it is likely that Becquerel concentrated his attention on uranium and its compounds because the mechanical theory of luminescence opened up the possibility that, precisely in the case of uranium and its compounds, a violation of Stokes's law could occur, and penetrating short-wavelength radiation could be emitted through a special type of phosphorescence.     

Effets d'analogues du chloramphénicol sur la différenciation de l'∄uf de l'oursinParacentrotus lividus

Summary The effects ofl-threo-chloramphenicol and thiophenicol on the differentiation of sea-urchin eggs are compared with those exerted byd-threo-chloramphenicol. Onlyd-threo-chloramphenicol caused vegetalization;l-threo-chloramphenicol inhibited development. These effects resemble those of nitrobenzene. Thiophenicol, differing fromd-threo-chloramphenicol by replacing the nitro group with a methylsulphonyl group, slows down development at high concentrations. The effects of chloramphenicol on oxidative phosphorylation and synthesis of proteins are discussed. It is suggested that both the steric configuration typed-threo of the side chain and the presence of a nitro group are necessary for the vegetalizing activity.     

Apparent arylsulfatase A activity in excretory fluids

Summary Arylsulfatase activity has been demonstrated in rat and human parotid and submandibular saliva indicating that oral bacteria are not the only source of salivary sulfatase activity. Activity was also observed in human sweat, tears and in snake venom.Acknowledgments. We extent appreciation to Drs.C. Dawes andK. Abe for assistance in saliva collection, to Dr.K. W. Stewart who provided fresh snake venoms and to Dr.E. T. Pritchard in whose laboratory this study was conducted. Supported by grant Nr. MT 3536 from MRC of Canada.     

Über Pflanzenwachstumsregulatoren

Summary Experiments withColeus Blumei andTropaeolum showed that triazine compounds inhibit the photosynthesis, and, consequently, prevent the accumulation of starch. The chloroplasts of starchfree coleus leaves kept on a solution containing sugars and simazine are able to form starch again.

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Mitteilung (siehe auch die zwei folgenden ArbeitenExer undRoth).     

Effects of glycolytic metabolites on preservation of high energy phosphate level and synaptic transmission in the granule cells of guinea pig hippocampal slices

The present study was undertaken to investigate whether neural activity of hippocampal slices can be preserved after replacingd-glucose with glycolytic intermediate metabolites such as lactate, pyruvate and citrate or with other sugars such as fructose, mannose, maltose, glucosamine, sucrose and galactose. As an index of neural activity, population spikes (PS) were recorded in the granule cell layers after electrical stimulation to the perforant path of guinea pig hippocampal slices. In addition, we determined the levels of ATP and creatine phosphate (CrP) in each slice after the replacement ofd-glucose with these substrates, and correlated it with the neural activity. Substrates other thand-glucose could not maintain the PS for even 20 min although the slices perfused with medium containing lactate, pyruvate, galactose, fructose and maltose maintained similar levels of ATP and CrP as in slices incubated in thed-glucose-containing medium. These results indicate thatd-glucose is essential for the preservation of synaptic activity in addition to its main role as the substrate for energy production to maintain the levels of high energy phosphates.     

Trypsin activity in the midgut ofSarcophaga ruficornis andMusca domestica (Diptera: Insecta)

Summary The pH and temperature for the optimum activity of trypsin from the midgut ofSarcophaga ruficornis andMusca domestica was 7.5 and 8.0 respectively and 50°C. The enzymic activity increased with the increase in incubation period and enzyme concentration.Thanks are due to Prof.R. Rakshpal for guidance.     

Intestinal uptake of ouabain and digitoxin in the milkweed bug,Oncopeltus fasciatus

Summary The absorption of ouabain and digitoxin into the gut of the milkweed bug was studied by a tissue-accumulation technique. Uptake of both compounds obeyed diffusion kinetics, was Na⁺ sensitive, and for digitoxin, was concentrative.The authors express their appreciation to Dr.James A. Slater and Ms.Flavia O'Rourke, Biological Sciences Group, University of Connecticut, Storrs, Conn. (USA) for supplying milkweed bugs. This work was supported by the University of Maine Honors Program and the University of Maine Agricultural Experiment Station.     

Isolation of sodium-complexing polypeptides from mammalian blood and cardiac muscle

Summary Two distinct polypeptides have been isolated from rat heart and ox blood. They are both found to be effective in forming complexes with sodium ions, and it is suggested that they may have a function in stabilizing sodium ion activity.Acknowledgments. We are indebted to ProfessorG. A. Gilbert, F.R.S. and to Dr.C. J. Lote for helpful discussion, and to the Royal Society for a Grant-in-aid which in part supported the investigation.     

Die Entwicklung der Valenzlehre und Alfred Werner

Summary Surveying the various concepts of valency which have been put forward sinceDalton for the classification of chemical phenomena, it is found that the principles have been either dualistic (Berzelius, Blomstrand, Arrhenius, Kossel) or unitarian (Gerhard, Couper, Kekulé). The phenomena of inorganic chemistry can be classified only by using dualistic concepts, whereas unitarian systems proved to be superior for the phenomena of organic chemistry. In the conceptions of G. N.Lewis and N.Sidgwick, a combination of dualistic and unitarian concepts in one theory was achieved by distinguishing two types of bonds (mobile-immobile, polar-non-polar, ioniccovalent). With the octet rule, ions as well as molecules (uncharged and charged) may be derived and it is readily understood that bonds may vary from extreme polarity to non-polar links.The coordination theory ofWerner neither fits into the dualistic nor the unitarian class of valency principles.Werner derives the compounds by using principal and auxiliary valencies (Haupt- und Nebenvalenzen) and distinguishes addition and insertion compounds (Anlagerungs- und Einlagerungsverbindungen). However, he avoids making any statement concerning the nature of the bonds, which makes his system very adaptable but difficult to grasp. Today it is readily understood thatWerner's principal valency characterizes the stoichiometry and his coordination number characterizes the structure of the compound in question without making any statement about the nature of the bonds involved. Because of thatWerner's concepts have survived and are indispensable even today, in spite of the rise of atomic physics which has changed our views on the nature of the chemical bonds so drastically.

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Paul-Karrer-Vorlesung, gehalten am 22. Juni 1966 zum Anlass der hundertsten Wiederkehr des Geburtstages vonAlfred Werner, dem Vorgänger von Professor Karrer auf dem Lehrstuhl für Allgemeine Chemie der Universität Zürich.     

Synthese und biologische Aktivität bradykininwirksamer Undeca-, Dodeca- und Tridecapeptide

Summary Several undeca-, dodeca- and tridecapeptides, analogues of the naturally occurring methionyllysyl-bradykinin, have been synthesized. The biological activities of the new compounds on the isolated rat uterus, guinea-pig ileum and rabbit blood pressure are presented.

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über Peptidsynthesen XXXIV. 7. Mitt. über Bradykinin- und Kallidin-Analoga. XXV. Mitt. über Peptidsynthesen, 6. Mitt. über Bradykinin- und Kallidin-Analoga:E. Schr?der, H.-S. Petras undE. Klieger, Liebigs Ann.679, 221 (1964).     

Nachweis von Corticosteroiden in menschlicher Placenta und Isolierung von 16α-Hydroxytestosteron

Summary The occurrence of cortisol, cortisone, 20-dihydrometabolites of cortisone and several other steroidlike compounds in fresh placental tissue is described. Neither aldosterone, corticosterone nor 11-dehydrocorticosterone has been found. One of the most abundant compounds present has been identified as 16-hydroxy-testosterone.

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184. Mitteilung über Steroide. 183. Mitteilung:E. H. Wehrli, M. Cereghetti, K. Schaffner, J. Urech undE. Vischer, Helv. chim. Acta44, im Druck (1961).     

9,10-Dihydroergotamine: Production of antibodies and radioimmunoassay

Summary Antibodies against 9,10-dihydroergotamine (DHE) were produced by immunizing rabbits with a conjugate of 6-nor-6-carboxymethyl-9,10-dihydroergotamine and bovine serum albumin. A highly specific and sensitive radioimmunoassay for DHE has been developed.We are greatly indebted to Dr.T. Fehr for the synthesis of 6-nor-6-carboxymethyl-9,10-dihydroergotamine, and to Dr.E. Schreier for providing us with 9,10-dihydroergotamine-[13-³H]-base of high specific activity.     

Central course of photic input in the ventral nerve cord of scorpion (Heterometrus fulvipes)

Summary The course of the photic input from the metasoma in the ventral nerve cord of scorpion was studied. The input was found to influence the activity in a large number of neurons in the nerve cord. The phenomenon of contralateral stimulation of units at various levels of the nerve cord has heen demonstrated.Acknowledgments. The electronic equipment used for the study was obtained with the help of Prof.T. H. Bullock and the late Prof.K. Pampapathi Rao who initiated me into this field of study, through a research grant from the USAFOSR to them. I am highly grateful to Prof.Bullock for permitting me to use the equipment. I am also grateful to Dr.A. R. Kasturi Bai for her kind encouragement and Dr.S. A. T. Venkatachari for his helpful comments.     

Immunpräzipitation Insulin-verwandter proteine mit ziegen-anti-insulinserum

Summary Bovine insulin, proinsulin, and intermediate form were prepared by Sephadex gelfiltration and chromatography on DEAE-cellulose. Using a goat anti-insulin serum, the cross-reactions of proinsulin and intermediate form could be shown by immuno-precipitation. A method is described for the separation of proinsulin from insulin in agar gel. New compounds related to proinsulin or insulin were found in human insulin preparations by means of immunoelectrophoresis.

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Wir danken Frl.B. Laars und HerrnD. Klatt für ausgezeichnete technische Mitarbeit.     

Uptake ofl-glutamate andl-aspartate in neurones and glial cells of cultured human and rat spinal cord

Summary Autoradiographic investigations on the uptake ofl-glutamate andl-aspartate have shown that the amino acids were taken up by neurones as well as by glial cells of cultured human and rat spinal cord. The activity of glutamate and aspartate varied considerably between individual neurones, whereas glial cells showed a more even distribution of the labelled amino acids. Our results suggest that both neurones and glial cells are involved in the uptake of amino acid transmitters.     

Zur Wirkung des Calciums auf die Myofibrillen-ATPase des Herzmuskels

Summary The inhibition of cardiac myofibrillar ATPase activity by EDTA can be completely reversed by Ca⁺⁺ under certain experimental conditions. This shows that there is no fundamental difference between the reaction of cardiac myofibrillar ATPase and the tension development of glycerinated cardiac fibres, as was supposed byBriggs andHannah on account of the results ofParker andBerger.     

Synthese der Spiroaminoketal-Gruppierung von Solanum-Alkaloiden

Summary The ring-E opened dihydro derivatives of tomatidine and soladulcidine give the corresponding N-chloroamines with N-chlorosuccinimide. Treatment of these compounds with sodium methoxide yields the spiroaminoketal alkaloids, tomatidine and soladulcidine respectively, in high yields, probably via instable C=N-unsaturated intermediates which undergo spontaneous stereospecific cyclisation.

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Solanum-Alkaloide. XIII. Mitteilung. XII. Mitteilung:K. Schreiber undH. Ripperger, Exper.16, 536 (1960).     

Rates of ethiodide formation and the stereochemistry of ajmaline at C-21

Résumé Les auteurs ont mesuré les vitesses de réaction entre l'ajmaline plus dérivés et l'iodure d'éthyle. Les conclusions stéréochimiques deTaylor au C-21 en ont été confirmées.

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For previous papers on rates of quaternary iodide formation of alkaloids see (a)M. Shamma and J. B. Moss, J. Amer. chem. Soc.83, 5038 (1961) and (b)M. Shamma andE. F. Walker Jr., Chem. & Ind.1962, 1866.

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Acknowledgments. The authors wish to thank Dr.W. I. Taylor of CIBA Pharmaceutical Company for the generous gift of the compounds used in this study, and the National Institutes of Health (Grant No. GM-10608-01) for financial assistance.