New tigliane and daphnane derivatives from Pimelea prostrata and Pimelea simplex

From the methanol extract of Pimelea prostrata, prostratin (I) and 2 autoxidation products have been isolated. They are tigliane derivatives and relatively nonirritant on the mouse ear. The irritant pimelea factor P5 (IIa) also with a tigliane skeleton and related to mancinellin (IIb), as well as the irritant diterpene ester pimelea factor P1 (IIa, simplexin) with daphnane skeleton, were found to be present in both P. prostrata and P. simplex. Further the irritant homologue of simplexin, pimela factor IIIb was detected in P. prostrata. Some biogenetic consequences of these findings are discussed.     

Cocarcinogens of the diterpene ester type fromCroton flavens L. and esophageal cancer in Curaçao

Summary From the roots ofCroton flavens L., 3 highly irritant and tumor promoting Croton factorsF ₁–F ₃ and the corresponding 3 cryptic Croton factorsF₁–F₃ were isolated and characterized as novel esters of 16-hydroxy- and 4-deoxy-16-hydroxyphorbol, respectively. These findings suggest that tumor promoters of the phorbol ester type, ingested through the widespread and frequent use ofCroton flavens according to local habits, may be causally related to the well recognized high rate of esophageal cancer on Curaçao.Dedicated to Prof. Dr H. P. Rusch, Director Wisconsin Clinical Cancer Center, Madison, Wis. USA, on occasion of his 70th birthday. We wish to thank Dr J.F. Morton, Morton Collectanea, University of Miami, Florida, USA, for kindly supplying us with the plant material.     

Stereoselectivity of oxotremorine antagonists containing a chiral pyrrolidine group

Summary Oxotremorine (Ia) and its succinimide analogue (IIa) have been substituted in the pyrrolidine ring with a methyl group in the 2- or 3-positions. The compounds are oxotremorine antagonists. The 2-methyl-substituted enantiomers show stereoselectivity, the S-isomers being the most active.     

Structure and stereochemistry of attenuol,a new lignan fromKnema attenuata (Wall.) Warb.

Summary A new lignan attenuol has been isolated from the bark ofKnema attenuata (Wall.) Warb. Its structure (I) is deduced on the basis of analytical and spectral data. The compound has been assigned the absolute configuration as 2S,3R-dimethyl-1S-(p-hydroxyphenyl)-6,7-methylenedioxytetralin (III).Contribution No. 487 from the Ciba-Geigy Research Centre.Acknowledgments. We thank Dr H. Fuhrer and Dr P. Moser of Ciba-Geigy Ltd. Basle for the NMR spectral data and ORD determinations and Dr S. Selvavinayakam and his colleagues for the analytical results.     

Luffariellolide,an anti-inflammatory sesterterpene from the marine spongeLuffariella sp.

Summary Luffariellolide (2) is a sesterterpene from the Palauan spongeLuffariella sp. that has useful anti-inflammatory properties. In contrast with the irreversible action of manoalide (1) on phospholipase A₂, luffariellolide (2) is a slightly less potent but partially reversible PLA₂ inhibitor.30 December 1986Acknowledgment We thank Edward Luedtke, Elise Clason and Ellen Snideman for performing some of the assays reported above. The sponge was identified by Dr. Klaus Rützler, Smithsonian Institution, Washington, D.C. The research was supported by grants from Allergan Pharmaceuticals and the California Sea Grant College Program (Projects R/MP-30 and R/MP-31).     

Isometachromin,a new cytotoxic sesquiterpenoid from a deep water sponge of the family Spongiidae

Isometachromin (1), a new sesquiterpene-quinone that is related structurally to metachromin C (2), and the known compounds ilimaquinone (3) and and 5-epi-ilimaquinone (4), were isolated from a deep water sponge in the family Spongiidae; the structure of isometachromin was elucidated by spectral methods. Isometachromin exhibits in vitro cytotoxicity against the human lung cancer cell line A 549 (IC₅₀=2.6 g/ml), but not against P 388 murine leukemia (IC₅₀10 g/ml) and also exhibits antimicrobial activity.This research is Harbor Branch Oceanographic Institution (HBOI) contribution number 911. We thank Drs S. A. Pomponi and M. Kelly-Borges (HBOI) for sponge taxonomy, and Dr P. McCarthy and T. Peterson (HBOI) for antimicrobial data.     

Fluorescence of blood cells of the tunicatesPhallusia mamillata andCiona intestinalis

Zusammenfassung Von den Blutzellen derPhallusia mamillata Cuvier zeigen nur die stark vakuolisierten (compartment cells) im UV-Licht eine stabile blaue Fluoreszenz ( _max =5200 und 4600 Å). Sie ist in den Zellgranula lokalisiert. Bei den Blutzellen vonCiona intestinalis L. tritt dagegen eine gelbe Fluoreszenz ( _max = 5900, 5200 und 4600 Å) auf, die nur von den Vanadocyten ausgeht. Diese Fluoreszenz, welche auch von den Testazellen der Oocyten gegeben wird, geht innerhalb einiger Minuten in die blaue Fluoreszenz über.

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This work has been carried out in the Stazione Zoologica, Napoli (director Dr.P. Dohrn) and in the Istituto di Biologia Generale e Genetica della Università di Napoli (director Prof. Dr.B. de Lerma). —M. de Vincentiis wishes to thank Dr,P. Dohrn for placing at his disposal a working place of the Consiglio Nazionale delle Ricerche, Roma. —W. Rüdiger thanks sincerely the Deutsche Forschungsgemeinschaft, Bad Godesberg, for providing grants, and Prof. Dr.H.-J. Bielig for his interest.     

Enantiomeric cannabinoids: stereospecificity of psychotropic activity

Summary The 1,1-dimethylheptyl homolog of (–)-(3R,4R)-7-hydroxy-delta-6-tetrahydrocannabinol (compoundII) is highly psychotropic in mice, rats and pigeons. The (+)-(3S,4S) enantiomer (III) was found to be psychotropically inactive at doses up to several thousand times those of the ED₅₀ of (II).We thank Dr A. Breuer and Mrs H. Amsalem for help with the syntheses. The research reported above was supported in Tucson by NIH grant NS 15441; in Uppsala by grants from the Swedish Medical Research Council (5757) and the Swedish Council for the Planning and Coordination of Research (84/2082); in Jerusalem by the Szold Foundation.Presented in part at a meeting at the US National Institute on Drug Abuse, Washington, D.C., October 1986, see NIDA Research Monographs79 (1987) 15.     

Two derivatives of farnesylacetone from the brown algaCystophora moniliformis

Summary Farnesylacetone epoxide (3) and the isomeric diketone (4) have been isolated from the brown algaCystophora moniliformis.Acknowledgment. We thank Dr K. Noack for CD measurements and interpretations and Mr K. Harada for algal identification.     

The identification of norlobariol,a new lichen constituent fromXanthoparmelia scabrosa (Tayl.) Hale

Summary Norlobariol (I) previously described as a synthetic product derived from norlobaridone (II) was isolated as a new metabolite fromXanthoparmelia scabrosa (Tayl.) Hale.Acknowledgment. The authors wish to acknowledge the assistance of Dr D. Galloway in identifying the lichen sample and Dr A.W. Campbell for the microanalytical data.     

Luffolide,a novel anti-inflammatory terpene from the spongeLuffariella sp.

Summary Luffolide (4) is a minor metabolite of the spongeLuffariella sp. from Palau. The structure of luffolide was determined by single crystal X-ray analysis. Luffolide is relatively unstable and undergoes a complex cyclization reaction to give the hexacyclic products5 and6. Luffolide (4) has some of the anti-inflammatory properties of manoalide (1): this may help to define the chemical reaction between manoalide (1) and phospholipase A₂.All crystallographic calculations were done on a PRIME 9950 computer operated by the Cornell Chemistry Computing Facility. Principal programs employed were: FOBS, a data reduction program by G.D. Van Duyne, Cornell University, 1987; MULTAN 80, and RANTAN 80, systems of computer programs for the automatic solution of crystal structures from X-ray diffraction data (locally modified to perform all Fourier calculations including Patterson syntheses) written by P. Main, S. E. Hull, L. Lessinger, G. Germain, J. P. Declercq and M. M. Woolfson, University of York, England, 1980 BDLS, an, anisotropic block diagonal least squares refinement written by K. Hirotsu, E. Arnold, and G. D. Van Duyne, Cornell University, 1987; PLUTO 78, a locally modified crystallographic illustration program by W. D. S. Motherwell, Cambridge Crystallographic Data Centre, 1978; and BOND, a program to calculate molecular parameters and prepare tables written by K. Hirotsu and G. Van Duyne, Cornell University, 1985.Acknowledgment. We thank the Government of the Republic of Palau for a scientific research permit. We thank Dr Klaus Rützler, Smithsonian Institution, Washington, D.C. for identifying the sponge and Mary Kay Harper for performing additional bioassays. This research was supported by grants from the Sea Grant College Programs of California [Projects R/MP-30 to DJF) and R/MP-31 (to RSJ)] and New York (to JC) and the National Institutes of Health (CA 24487 to JC).     

Antimicrobial activity of carbazole derivatives

Summary Glycozoline and girinimbine isomers (IV andVII) were synthesized and their activity against 2 bacterial strains, viz.E. coli andS. aureus, and 2 fungal strains, viz.C. albicans andA. niger were studied. The hydroxy synthons (III) were also tested. The authors are thankful to Dr B.N. Apte, Association of Microbiologists of India, Bombay Unit, for providing some of the organisms, to Prof. A.K. De, Indian Institute of Technology, for financial assistance, to Prof. G. D. Shah, Department of Chemistry, Indian Institute of Technology for guidance, encouragement and helpful discussions.     

Flying insects: model systems in exercise physiology

Insect flight is the most energy-demanding exercise known. It requires very effective coupling of adenosine triphosphate (ATP) hydrolysis and regeneration in the working flight muscles.³¹P nuclear magnetic resonance (NMR) spectroscopy of locust flight muscle in vivo has shown that flight causes only a small decrease in the content of ATP, whereas the free concentrations of inorganic phosphate (P _i ), adenosine diphosphate (ADP) and adenosine monophosphate (AMP) were estimated to increase by about 3-, 5- and 27-fold, respectively. These metabolites are potent activators of glycogen phosphorylase and phosphofructokinase (PFK). Activation of glycolysis by AMP and P _i is reinforced synergistically by fructose 2,6-bisphosphate (F2,6P₂), a very potent activator of PFK. During prolonged flight locusts gradually change from using carbohydrate to lipids as their main fuel. This requires a decrease in glycolytic flux which is brought about, at least in part, by a marked decrease in the content of F2,6P₂ in flight muscle (by 80% within 15 min of flight). The synthesis of F2,6P₂ in flight muscle can be stimulated by the nervous system via the biogenic amine octopamine. Octopamine and F2,6P₂ seem to be part of a mechanism to control the rate of carbohydrate oxidation in flight muscle and thus function in the metabolic integration of insect flight.Dedicated to Dr. Ernst Zebe, Emeritus Professor of Zoology (University of Münster) on the occasion of his 70th birthday.     

On the synthesis of serine and homoserine samples asymmetrically labelled with tritium and deuterium in the hydroxymethylene group

Summary (1 R) [1-³H,²H₁] 3-Phenylpropanol, the key intermediate in the synthesis of (4 R) [4-³H,²H₁] D, L-homoserine and of the (4 S)-isomer, is obtained from (1 S) [1-²H₁] 3-phenylpropanol and (1 RS) [1-³H] ethanol upon incubation with yeast alcohol dehydrogenase and NAD⁺; under similar conditions 2-phenylethanol undergoes very small exchange with [1-²H₂] ethanol.     

Two new kaempferol 3,7-diglycosides and kaempferitrin in the fernAsplenium trichomanes

Summary The fronds of the fernAsplenium trichomanes contain kaempferol 3,7-dirhamnoside (1) and the new compounds kaempferol 3-O-a-rhamnoside-7-O-a-arabinoside (2) and kaempferol 3-O-a-arabinoside-7-O-a-rhamnoside (3). The presence of the above flavonoids has been shown by spectroscopic methods and chemical degradations.Acknowledgments. The author thanks Prof. H. Wagner (Institut für pharmazeutische Arzneimittellehre der Universität München, München) for a sample of kaempferol 3,7-dirhamnoside, Dr K. R. Markham (Chemistry Division, D.S.I.R., Petone, New Zealand) for a gift of pectinase and Mr A. D'Urso (Botanic Institute, University of Catania) for help in acquiring the plant material.     

Furospongolide,a new C21 furanoterpene from a marine organism

Summary The structure of a new linear C₂₁ furanoterpene, furospongolide (1), obtained from the marine spongeDysidea herbacea, was determined by spectral means.We thank Professor J. Vacelet for the identification and Dr Loya and Mr Benayahu for the collection of the sponge.     

Furodendin,a C22 degraded terpene from the spongePhyllospongia dendyi

Summary The structure of furodendin (5), a minor secondary metabolite of the spongePhyllospongia dendyi, has been solved by spectral methods. Furodendin is probably derived, biosynthetically, by elimination of a C₃ unit from a C₂₅ geranyl-farnesol precursor.Acknowledgment. We thank Dr C. Evans for sponge identification, RRIMP Museum number FN 1516/000.     

Semi-synthesis of A23187 (calcimycin) analogs

Summary The cleavage of A23187 to give a synthon (4) and the semi-synthesis from (4) of 2 Des-N-methylamino A23187 isomers (7a,b) are described. The antibiotic activities of the acids analogous to A23187(1), (2), (7a), (7b) are compared.Acknowledgment. The authors are very grateful to Drs G. Dauphin and J.Y. Lallemand for the NMR-spectra at 400 MHz performed in Gif-sur-Yvette, To Dr J.G. Gourcy and Mrs G. Kergomard for technical assistance.     

Anthraquinone pigments from a conidiating mutant ofTrichoderma viride

Summary Two pigments responsible for the yellow-orange color of a brown conidiating mutant of the deuteromyceteTrichoderma viride were isolated and spectroscopically identified as 1,3,6,8-tetrahydroxyanthraquinone (I) and 1-acetyl-2,4,5,7-tetrahydroxy-9,10-anthracenedione (II). Both compounds are known substances but were not yet reported as metabolites of this fungal species. Their relationship to other anthraquinones produced byT. viride is discussed.Dedicated to Dr Z. Vanek, on the occasion of his 60th birthday.Upper case letters denote multiplicity arising from the directly bonded protons, lower case letters that from the geminal and vicinal couplings.