Highly irritant ingenane type diterpene esters fromEuphorbia cyparissias L.

Summary From the roots ofEuphorbia cyparissias L. a highly irritant diterpene ester fraction was isolated and further resolved into its constituents. Together with some less active and some inactive isomers, the pure Euphorbia factors were characterized as new diesters of 13-hydroxyingenol and as triesters of the new 13,19-dihydroxyingenol. The Euphorbia factorsCy ₆,Cy ₁₁ andCy ₁₄ are the strongest irritants of the ingenane ester type hitherto known,Cy ₁₁ being at least as active as the standard diterpene ester type irritant 12-O-tetradecanoylphorbol-13-acetate (TPA).Acknowledgments. We are greatly indebted to the Wilhelm and Maria Meyenburg Foundation for financial support for the supply of plant material required for this investigation.The results were partially presented by H.H.O. at the 17. Hauptversammlung der Gesellschaft Deutscher Chemiker. München, 12.–16.9.1977. PhD-thesis. University of Heidelberg, 1978.     

Constituents ofCannabis sativa L. XXI: Estrogenic activity of a non-cannabinoid constituent

Summary A non-cannabinoid phenol (4,4,dihydroxy-5-methoxybibenzyl) increased uterine weight in prepubescent female rats, suggesting non-cannabinoids contribute to the estrogenic effects ofCannabis.Acknowledgments. This research was supported by Contract 271-78-3527 from the National Institute on Drug Abuse and by the Research Institute of Pharmaceutical Sciences, University of Mississippi. The authors are grateful to Karen S. Tomaszewski for technical assistance.     

Constituents of labiatae XIX. Structure of galdosol,a new diterpene fromSalvia canariensis L.

Résumé Le nouveau diterpène galdosol (I) a été isolé de laSalvia canariensis L. et sa structure déterminée comme 7-oxo-11, 12-dihydroxy-8, 11, 13-abiétatrién-20, 6-olide.     

Identification and electroantennographic activity of sex-specific geranyl esters in an abdominal gland of femaleAgriotes obscurus (L.) andA. lineatus (L.) (Coleoptera,Elateridae)

Summary Both geranyl hexanoate and geranyl octanoate were identified by GC/MS as the major volatiles in a hitherto uncharacterized abdominal gland in females inAgriotes obscurus. Only geranyl octanoate was found inA. lineatus. In EAG tests performed onA. obscurus males, geranyl butanoate and geranyl hexanoate elicited the strongest antennal responses.Financial assistance was donated by The Bank of Sweden Tercentenary Foundation and the Axel and Margaret Ax: son Johnson Foundation. We thank B Baur for statistical advice.     

The structure of amoorastatone and the cytotoxic limonoid 12-hydroxyamoorastatin.

2 new limonoid-type terpenes have been isolated from an aqueous extract of seeds produced by the Eastern Himalayan (India) plant Aphanamixis grandifolia B1. By interpreting principally mass spectral and nuclear magnetic resonance data, the structures of 12-hydroxyamoorastatin (2b) and amoorastatone (3) were elucidated. Unequivocal evidence for the 12-hydroxyamoorastatin structural assignment was obtained by chemical conversion to sendanin (4). Amoorastatin derivative 2b was found to significantly inhibit growth of the murine P388 lymphocytic leukemia cell lines but amoorastatone in the same system was inactive. In a comparative biological study, sendanin (4) and anthothecol (7) were also found significantly to inhibit growth of the P388 cell line, while rohitukin (8) and limonin (9) were found to be inactive.     

Further new diterpene esters from the irritant and cocarcinogenic seed oil and latex of the caper spurge (Euphorbia lathyris L.)

Zusammenfassung Ein Diacetat-Benzoat und ein Diacetat-Nicotinoat des neuen Diterpens «Lathyrol» sowie weitere Ester des Diterpens Ingenol wurden aus dem Samenöl bzw. dem Latex vonEuphorbia lathyris L. isoliert. Die chemische Struktur von Lathyrol wurde mittels spektraler Daten aufgeklärt. Lathyrol ist die Muttersubstanz der beiden bereits früher ausE. lathyris isolierten makrozyklischen Diterpene 6.20-Epoxy-lathyrol und 7-Hydroxy-lathyrol. Es wird ein Biogeneseweg für Diterpene aus Euphorbiaceen vorgeschlagen.

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Measurements and discussions of NMR spectra by Prof.M. Anteunis, Gent, and Dr.A. Mannschreck, Heidelberg, are gratefully acknowledged.     

Retinol and retinyl esters in pigment epithelium of rats with inherited retinal degeneration.

A comparative study of the retinol and retinyl ester concentrations was performed in the retinal pigment epithelium of the normal and affected rats. Our findings indicate that in dystrophic rat retinol content increases, whereas the amount of retinyl esters is always lower than normal. An hypothesis can be made on the deficiency of enzymic activities which regulate retinol retinol and retinyl esters levels in the pigment epithelium.     

Alkylating esters VII. The metabolism of iso-propyl methanesulphonate and iso-propyl iodide in the rat

Zusammenfassung Nachweis, dass die im Rattenharn auftretenden Metaboliten Isopropyljodid und Isopropylmethansulfonat für einen unterschiedlichen Wirkungsmechanismus der Substanzen in vivo sprechen. Aus Isopropylmethansulfonat entsteht durch einen monomolekularen Prozess das äusserst reactive Dimethylcarboniumion, während Isopropyljodid aufgrund einer bimolekularen Reaktion haupsächlich durch Hydrolyse entgiftet wird.     

Immunocytology of alpha-endorphin positive hypothalamic fibers of Carassius auratus L. and Cyprinus carpio L.]

An immunocytological study of the basal hypothalamus of Carassius auratus and Cyprinus carpio with an alpha-endorphin antiserum shows the different nerve processes belonging probably to the immunoreactive cells of the lateral part of the N.L.T. According to their pathways, two main fibre tracts have been distinguished: many fluorescent fibres converge towards the pituitary gland into which they enter, other fibres run caudally through the tuber towards the nucleus tuberis inferior (Baumgarten and Braak) where they could not be followed further.     

Frontal ganglion and water balance inPeriplaneta americana L.

Zusammenfassung Der Gewichtsverlust bei frontalganglionektomierten Schaben innerhalb von 24 h im Exsikkator ist wesentlich grösser als derjenige bei scheinoperierten Tieren. Er erreicht Werte, wie sie bei toten Tieren auftreten. Der Gewichtsverlust ist mit einer signifikanten Zunahme der Gefrierpunktserniedrigung in der Hämolymphe verbunden. Durchtrennung beider Frontalkonnektive hat dieselbe Wirkung wie Ganglionektomie.     

The structure of amoorastatone and the cytotoxic limonoid 12-hydroxyamoorastatin

Summary 2 new limonoid-type terpenes have been isolated from an aqueous extract of seeds produced by the Eastern Himalayan (India) plantAphanamixis grandifolia Bl. By interpreting principally mass spectral and nuclear magnetic resonance data, the structures of 12-hydroxyamoorastatin (2b) and amoorastatone (3) were elucidated. Unequivocal evidence for the 12-hydroxyamoorastatin structural assignment was obtained by chemical conversion to sendanin (4). Amoorastatin derivative2b was found to significantly inhibit growth of the murine P388 lymphocytic leukemia cell lines but amoorastatone in the same system was inactive. In a comparative biological study, sendanin (4) and anthothecol (7) were also found significantly to inhibit growth of the P388 cell line, while rohitukin (8) and limonin (9) were found to be inactive.Part 63 of the series Antineoplastic Agents. For the previous contribution refer to G.R. Pettit, T.S. Krupa and R.M. Reynolds, Int. J. Peptide Protein Res., in preparation. The present investigation was supported in part by Public Health Research Grant No. CA-16049-05 from the National Cancer Institute, the Fannie E. Rippel Foundation, Mrs Mary Dell Pritzlaff, the Spencer T. and Ann W. Olin Foundation, Mr John F. Schmidt, and the Phoenix Coca-Cola Bottling Company.     

Synthetic simulation of nonribosomal peptide biosynthesis. A dual role of alkylthiol esters in peptide synthesis

Summary Coupling of peptide alkylthiol esters with amino acid derivatives in the presence of pivalic acid or 2-hydroxypyridine proceeds without racemization. A dual role of alkylthiol esters as protective and reactive functions in peptide synthesis was well proved.