Milanjilactones A and B,two novel cytotoxic norditerpene dilactones fromPodocarpus milanjianus Rendle

Summary Two new cytotoxic norditerpene dilactones, milanjilactones A(3) and B(4) have been isolated from the stem bark ofPodocarpus milanjianus Rendle and characterized, on the basis of spectroscopic evidence, as 1,2-dehydro derivatives of nagilactones F(1) and G(2).The authors acknowledge the technical assistance of Ms Teresa K. Lightner. Part 11 in the series Potential Antitumor Agents.     

Metabolism in Porifera. IX. Studies on the biological conversion of cholesterol into 19-nor-cholestanol by the spongeAxinella polypoides

Summary The conversion of cholesterol into 19-nor-5-cholestan-3-ol by the spongeAxinella polypoides involves a partial loss (40%) of the 3-hydrogen atom; moreover administration to the sponge of [4-¹⁴C]cholesterol tritiated at C-4 and C-7 showed that the 4- and 7-hydrogen atoms are retained in this conversion. A competitive uptake experiment, [4-¹⁴C]cholesterol vs. [7-³H₂]5-cholestanol, showed that the sponge utilized exclusively cholesterol for the production of 19-nor-5-cholestan-3-ol.Part of this work has been presented at the Nato Conference on Marine Natural Products (Jersey, Great Britain, October, 1976).-This contribution is part of the Programma finalizzato Oceanografia e Fondi marini-sottoprogetto Risorse biologiche C.N.R. Italy.     

Ethical principles and guidelines for experiments on animals

Editorial Note The following Ethical principles and guidelines for scientific experiments on animals are reprinted here with the kind permission of the Commission appointed to formulate the guidelines and both Swiss Academies represented on the Commission. They form the basis on which Editors and referees judge whether studies involving experimentation on animals can be considered for our journal. Authors are asked to adhere strictly to these rules.EXPERIENTIA fully endorses article 5.7 wherein Scientific journals are urged not to accept the results of such experiments [i.e. those which contravene the ethical principles and the present guidelines] for publication.     

Starfish saponins. Part 101. Further 24-O-glycosidated steroids from the starfishHacelia attenuata

Summary On the basis of comparative spectral data, the structures of 3 novel steroidal glycosides from the Mediterranean starfishHacelia attenuata have been elucidated as3, 4 and5. These are further examples of a novel group of 24-O-glycosidated steroids recently encountered in the same species and in the Pacific speciesProtoreaster nodosus.Part 9. L. Minale, C. Pizza, R. Riccio and F. Zollo, Experientia39 (1983) 567. This contribution is part of the Progetto Finalizzato Chimica fine e secondaria del C.N.R., Roma.Acknowledgments. We thank Prof. K. Nakanishi, Columbia University, New York, for FD-mass spectral analyses, the Centro Interfacoltà di Metodologie Chimico-Fisiche for 270 MHz NMR facilities, and Miss R. Aquino for part of the experimental work.     

K252a: A new blocker of the cell-cycle at G1 phase in a human hepatoma cell line

The administration of 200 nM K252a to HuH7 suppressed the proliferation of the cells almost completely. The uptake of [³H]thymidine was inhibited, and flow cytometry revealed only one peak at 2C on day 3 after treatment with 100 nM K252a. The expression of proto-oncogene c-myc was not reduced. Despite the blockage at G1, both the size of the cells and the amount of cell protein had increased by 4 times by day 3 after treatment with K252a, while the cells secreted albumin and -fetoprotein into the medium as usual. These results show that K252a can increase the cell size of HuH7 without losing its function by blocking the cell cycle at G1 phase.     

Cardenolide glycosides from the adults and eggs ofChrysolina fuliginosa (Coleoptera: Chrysomelidae)

Besides the known sarmentogenin 3-O--D-allopyranoside (1) and digitoxigenin-3-O-[-D-xylopyranosyl-(14)-2, 3-di-O-acetyl--D-allopyranoside] (4), four new cardiac glycosides (2, 3, 5 and6) have been isolated from the defensive glands of adults ofChrysolina fuliginosa. The structures of the new compounds were determined by¹H NMR at 600 MHz and FABMS. Compounds1–6, present in the adults ofC. fuliginosa, have also been identified in the eggs.     

A new proanthocyanidin from the stem bark ofAcacia suma

Summary From the stem bark of Acacia suma, a new proanthocyanidin (1) with a C–C linkage between the 4-position of 3, 3, 4, 5, 5, 7-hexahydroxyflavan and the 8-position of the (–)epicatechin part was isolated.Part of this work was done at Allahabad University, Chemical Laboratories, and the author is grateful to Prof. R. D. Tiwari for encouragement and valuable discussion.     

Heterocyclic steroids. Steroidal pyrimidines

Zusammenfassung Die erste Synthese eines Steroid-Analogen, in welchem Ring A zu einem Pyrimidin umgewandelt wurde, wird beschrieben. Die wichtigste Zwischenstufe 4b wurde durch Abbau von 19-nor-Testosteron gewonnen. Kondensation von 4b mit Thioharnstoff führte zu 17-Acetoxy-2,4-diazaestr-4-en-1-on-3-thion (5).

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(a) This research was supported by U.S. Public Health Service Grant No. A-5326; (b) Part IV of Heterocyclic Steroids. Part III, seeE. Caspi, P. K. Grover, andD. M. Piatak, Chem. and Ind., in press.

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Recipient Public Health Service Research Career Program Award CA-K3-16614 from the National Cancer Institute.     

The synthesis of isohalfordin

Zusammenfassung Die Synthese von Isohalfordin (3,4, 8-Trimethoxyfuro[3,2:6, 7]cumarin) aus 6,7-Dihydroxy-2, 3-dihydrobenzo[b]furan wird beschrieben.     

Metal complex formation by nicotianamine,a possible phytosiderophore

Summary The acid dissociation constants of nicotianamine (1) (pK₁=6.97, pK₂=9.13, pK₃=9.75; 0.1 M KClO₄, 25°C) and the stability constants for its 11 complexes with bivalent metal ions (log K_Cu=18.6, log K_Ni=16.1, log K_Co=14.8, log K_Zn=14.7, log K_Fe=12.1, log K_Mn=8.8, log K_Mg4.5; 0.1 M KClO₄, 25°C) were determined using potentiometric titrations in aqueous solution. Fe(III)-nicotianamine complexes were not detected under the same experimental conditions.Part 13 in the series On the normalizing factor for the tomato mutantchloronerva, for part 12 see Ripperger et al.⁴.     

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.     

A new tryptophan derived alkaloid fromEvodia rutaecarpa (Juss.) Benth. et Hook

Summary The first tryptophan-derived indolopyridoquinazoline alkaloid has been isolated from the fruits ofEvodia rutaecarpa (Jussieu) Bentham et Hook. Its structure is deduced on the basis of spectral data and enantioselective synthesis. The compound has been assigned the absolute configuration (7S,13bS)-7-carboxy-8,13,13b,14-tetrahydro-14-methylindolo[2,33,4]pyrido[2,1-b]quinazolin-5(7H)-one.     

A simple synthesis of (E)-3-formylbut-2-enenitrile,and its use as a precursor of isotope-labelled zeatin and (±) dihydrozeatin

Summary (E)-3-Formylbut-2-enenitrile (4) is synthesized in 2 steps by reacting pyruvaldehyde dimethylacetal and acetonitrile in the presence of sodium methoxide, followed by acid hydrolysis to give 58% overall yield on distillation. The aldehyde4 can be stepwise and selectively reduced to (E)-3-hydroxymethylbut-2-enylamine (7a) in 37% total yield or exhaustivelyb reduced in 1 step to (±)-4-hydroxy-3-methylbutylamine (6) in 46% total yield. Compound7a and6 can be condensed with 6-chloropurine to give zeatin and (±)dihydrozeatin respectively. This provides a readily accessible method for isotope-labelled zeatin and its derivatives at side chain.Contribution No. 1064, Alberta Research CouncilProcess for the Preparation oftrans-3-formylbut-2-enenitrile S. Chen and J. MacTaggart, patent applicatioin registered in Canada and the United States of America.Acknowledgment. The author thanks Mr J. M. MacTaggart and Mrs C. M. Goulet for valuable experimental assistance and Dr R. M. Elofson for helpful discussions.     

Biosynthesis of 1-aminocyclopropanecarboxylic acid: Steric course of the reaction at the C-4 position

Summary Under the action of the appropriate synthase from ripe tomatoes a 11 mixture of (3S, 4R)-[3,4-²H₂] and (3R, 4S)-[3,4-²H₂]-(2S)-adenosylmethionine is transformed into a 11 mixture of the two meso forms of [²H₂]-1-aminocyclopropanecarboxylic acid, a result which proves the operation of an inversion mechanism and which is consistent with direct nucleophilic displacement of the leaving group in the substrate.     

Effect of 3 polyphenolic compounds against ear-rot of corn incited byFusarium moniliforme Sheld

Summary Anti-F. moniliforme activity of 3 non-toxic polyphenolic compounds, viz. mangiferin, 1,3,6,7-tetrahydroxyxanthone, and 2,2,4-trihydroxybenzophenone, was evaluated. The mycotoxin-producing fungus incited ear-rot in sweet corn in fields and during storage. The test compounds provided different degrees of protection to sweet corn from the ingress of the fungus. Additionally, noteworthy postinfectional curative action was observed in the case of the trihydroxybenzophenone.Part 9 in the series Toxic substances produced byFusarium. For part 8 see S. Ghosal, K. Biswas and B.K. Chattopadhyay, Phytochemistry17, 689 (1978).     

Zur Synthese des Batrachotoxinins: Synthese von 3β-Acetoxy-16β, 20β-dihydroxy-4′-methyl-18-nor-5β, 14β-pregnano[13,14-f]hexahydro-1′,4'-oxazepin-3′-on(20a)

Summary The synthesis of 3-acetoxy-16, 20-dihydroxy-4-methyl-18-nor-5, 14-pregnano[13,14-f]hexahydro-1, 4-oxazepin-3-one (20a) is described.     

Labelling of steroids in axillary sweat after administration of3H-Δ5-pregnenolone and14C-progesterone to a healthy man

Résumé L'administration intraveineuse du prégnène-3-ol-20-one[7-³H]- ⁵ avec le progestérone[4-¹⁴C] à un homme sain amena la sécrétion d'autant de radioactivité dans la sueur des aiselles que dans la plupart du reste du corps. Le prégnénolone- ⁵, l'androstène-3,17-dione- ⁴ et le déhydroépiandrostérone furent les principaux stéroïdes marqués identifiés comme partant des deux sources de sueur.

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Acknowledgments. The author expresses grateful thanks to the subject (A.C.) who subjected himself to this experiment, and to Mr. D. A. A.Wilson for his technical assistance.     

Identification of (3R,4R)-gD 1(6) as an isolation artefact of cannabinoid acids formed by callus cultures ofCannabis sativa L

Summary For the first time we have isolated a major psychoactive cannabinoid, (3R, 4R)- ¹⁽⁶⁾-tetrahydrocannabinol3 from callus cultures ofCannabis sativa L.3 was obtained as an artefact of the actually formed (3R, 4R)- ¹-tetrahydrocannabinol-3- and/or 5-carboxylic acids1 and2 by subjecting the culture material to a decarboxylation step prior to extraction. No attempt was made to isolated acids1 and2. The identity of3 was confirmed by comparison with an authentic sample of (3R, 4R)- ¹-tetrahydrocannabinol. Culture conditions, isolation procedure and identification of the cannabinoid are described.Acknowledgment. The authors are greatly indebted to Dr W. Heller and Dr G. Schroeder-Frey for deriving the callus cultures from seedlings ofC. sativa and to Prof. N. Amrhein for valuable gifts of culture media and growth regulators.     

Defensive steroids from a carrion beetle (Silpha americana)

Summary The defensive anal effluent discharged bySilpha americana in response to disturbance contains a mixture of steroids stemming from a glandular annex of the rectum. The compounds have been characterized as 15-hydroxyprogesterone (1, principal component), 5-pregnan-15-ol-3, 20-dione (2), 5-pregnan-3, 15-diol-20-one (3), 5-pregnan-7, 15-diol-3,20-dione (4), 5-pregnan-3, 7, 15-triol-20-one (5), 5-pregnan-16-ol-3,20-dione (6), and 5-pregnan-3, 16-diol-20-one (7), none previously found in insects. Bioassays with jumping spiders showed compounds1 and6 to be feeding deterrents at the 1 g level.Paper No. 78 of the series: Defense Mechanisms of Arthropods. Study supported by NIH (Grants AI-02908, AI-12020). We thank Maura Malarcher and Maria Eisner for excellent technical help, and the Squibb Institute of Medical Research for samples of authentic reference compounds.