Helminthosporoside,a host-specific toxin fromHelminthosporium sacchari: A structure revision and a new partial structure

Summary Reevaluation of the previously proposed structure of helminthosporoside, a host-specific toxin fromHelminthosporium sacchari, reveals a sesquiterpenoid bis-digalactoside. The carbohydrate portion of the toxin was characterized by¹³C-NMR spectroscopy, methylation analyses, FD and FAB mass spectroscopy. The ring size and anomeric configuration of the galactose moieties were determined by utilizing a¹³C-NMR structural analysis method. A new partial structure is proposed.Acknowledgment. We extend special thanks to C.E. Costello, Department of Chemistry, M.I.T., Cambridge, MA, for FD mass spectral analyses, and to C.E. Ballou, Department of Biochemistry, University of California, Berkeley, CA, for FAB mass spectral analyses. We submit sincere appreciation to both V.N. Reihold, Harvard Medical School, Boston, MA, and P. Albersheim, Department of Chemistry, University of Colorado, Boulder, CO, for methylation analyses. We thank J.S. Frye at the Colorado State University Regional NMR-Center, funded by National Science Foundation grant No. DHE 78-18581, Department of Chemistry, Colorado State University, Fort Collins, Co, for high resolution CMR and NMR, and we are grateful to P.W. Jennings, Department of Chemistry, Montana State University, Bozeman, Mt, for total carbon analyses. This work was supported in part by a Herman Frasch Foundation grant to G.A. Strobel, by NSF grant PCM-78-22517, and funds from the Montana Agricultural Experiment Station. B.P. Mundy acknowledges the partial support of NSF (ISP-801149).     

Creatol (5-hydroxycreatinine), a new toxin candidate in uremic patients

Both 5-hydroxy-1-methylhydantoin (3) and the hitherto unrecognized 5-hydroxycreatinine (2-amino-5-hydroxy-1-methyl-imidazol-4(5H)-one or creatol) (6) can be isolated from the urine of uremic patients, in whom these compounds probably arise as oxidative metabolites of creatinine (1). The enhanced production of the well-known uremic toxin, methylguanidine (8), from creatinine (1) in such patients, almost certainly occurs via the newly recognized metabolite.     

Phallolysin,ein hochmolekulares toxin ausAmanita phalloides

Summary Phallolysin, a toxic hemolysin of high molecular weight, was isolated from aqueous extracts ofAmanita phalloides. Its properties are discussed.     

Reticulol,a new metabolic isocoumarin

Zusammenfassung Die Struktur des ausStreptomyces rubreticulae isolierten neuen Isocumarins, Reticulol, ist als 3-Methyl-6,8-dihydroxy-7-methoxyisocumarin ermittelt worden.     

Baluchistine,a new bisbenzylisoquinoline alkaloid

Summary The new phenolic bisbenzylisoquinoline alkaloid (+)-baluchistine, found inBerberis baluchistanica Ahrendt (Berberidaceae), has been assigned structure1. O-Methylation using ethereal diazomethane yields (+)-obaberine (2). Baluchistine is the 1 alkaloid of the oxyacanthine-berbamine group to incroporate a free phenolic function at C-6.this project was supported by NIH research grant CA-11450, awarded by the National Cancer Institute, PHS/DHEW.     

5-Azacytidine,a new,highly effective cancerostatic

Zusammenfassung Die hohe bakteriostatische und cancerostatische Wirkung eines neuen Antimetaboliten, 5-Azacytidin, wird beschrieben.     

o-N-diisopropylaminoethoxy-butyrophenone,a new local anaesthetic drug

Riassunto Da una serie di-fenossietilamine acilate è stata selezionata una nuova sostanza e cioè l'o-N-diisopropylaminoetossibutirrofenone, che possiede elevate proprietà anestetiche locali di superficie, per infiltrazione e tronculari. Si sono comparate le attività anestetiche e la tossicità del nuovo composto con quelle della cocaina e della procaina.     

Botulinum toxin as a carrier for oral vaccines

Botulinum toxin is an unusually potent substance that acts on the nervous system to produce the clinical outcome of flaccid paralysis. To produce this effect, the toxin ordinarily proceeds through two separate but essential sequences of events. During the first, the toxin is ingested, it traverses a portion of the gastrointestinal system and then it is transcytosed from the lumen of the gut to the general circulation. During the second, circulating toxin binds to peripheral cholinergic nerve endings, it is endocytosed and then it acts as a metalloendoprotease to cleave polypeptides that are essential for exocytosis. Although botulinum toxin is antigenic, it ordinarily does not evoke an immune response during or after cases of oral poisoning. This is due to the fact that the dose of toxin that produces flaccid paralysis—and potentially death—is less than the dose needed to evoke an antibody response. In the recent past, the techniques of molecular biology have been used to generate an expression product of botulinum toxin that retains the ability to escape the gut and reach the general circulation, retains the ability to evoke an immune response, but has lost the ability to produce neurotoxicity. This modified toxin may have two clinical applications. The expression product itself may have utility as an oral vaccine against botulism. Beyond this, the modified toxin, or a truncation mutant of the toxin, may have utility as a carrier in the construction of other oral vaccines. Both potential applications could lead to the expression of oral vaccines in common foods. Received 29 December 1998; received after revision 22 March 1999; accepted 24 March 1999     

Palinurin,a new linear sesterterpene from a marine sponge

Summary The structure of a new linear sesterterpene, palinurin (1), obtained from the marine spongeIrcinia variabilis, was determined by spectral and chemical means.This work was carried out at the Progetto Finalizzato Oceanografia e Fondi Marini, C.N.R., Roma. We thank Professor M. Sarà (University of Genova) for the identification of the sponge, Mr C. Di Pinto for¹H-and¹³C-NMR, Mr G. Scognamiglio for technical assistance.     

Nifurpipone,a new nitrofuran with a large antimicrobial spectrum

Riassunto Il nifurpipone (5-nitro-2-furaldeide N'-metil-N-piperazino-acetidrazone) è un nuovo nitrofuranico a largo spettro antibatterico, escreto con le urine e quindi potenzialmente indicato nelle infezioni delle vie urinarie.     

Metabolism of GS 13005, a new insecticide

Résumé Le métabolisme de l'insecticide GS 13005 (marqué par le C¹⁴ dans l'hétérocycle) fut étudié chez l'animal et dans la plante. Une conversion considérable de cette molécule en CO₂ fut constatée dans tous les deux. En plus aucune accumulation de l'insecticide intact ou de ses produits métaboliques n'a pu être observée, ni dans la plante, ni dans l'animal.

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GS 13005 is the active ingredient of a new insecticide of J. R. Geigy S.A., Basle, Switzerland, registered under the Trade mark of Supracide.     

Tartessol,a new diterpene fromSideritis grandiflora Salzm

Résumé Un nouveau diterpène tartessol (1) a été isolé de laSideritis grandiflora Salzm. (Labiées) est sa structure est proposée comme étantent-14-acétoxy-15-beyèren-18-ol.

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Part XVIII in the series Studies on diterpenes from genusSideritis. For Part XVII seeT. G. de Quesada, B. Rodríguez andS. Valverde,Phytochemistry, in press.

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The authors thank Dr.J. Borja, Botany Department, Faculty of Pharmacy, Madrid, for the collection and botanical classification of the plant material and Dr.Juana Bellanato, Institute of Optics, C.S.I.C., Madrid, for the high resolution IR spectra.     

Reflexine,a new indole alkaloid ofRauwolfia reflexa

Summary Reflexine, a new indole alkaloid, has been isolated from the leaves ofRauwolfia reflexa Teijsm. and Binn. From spectral studies, chemical reactions and correlation with seredamine, reflexine is shown to be its C-17 epimer (IV).Grateful thanks are accorded to ProfessorR. H. Thomson, Dr.R. T. Brown, Dr.Nitya Nand and Dr.S. C. Pakrashi for spectral measurements. Financial assistance from CCRIMH, New Delhi, and UGC, New Delhi, are also thankfully acknowledged.     

Anthrax lethal toxin: a weapon of multisystem destruction

Lethal toxin (LT) is a major virulence factor secreted by anthrax bacteria. It is composed of two proteins, PA (protective antigen) and LF (lethal factor). PA transports the LF inside the cell, where LF, a zinc-dependent metalloprotease cleaves the mitogen activated protein kinase kinase (MAPKK) enzymes of the mitogen activated protein kinase (MAPK) signaling pathway, thereby impairing their function. This disruption of the MAPK pathway, which serves essential functions such as proliferation, survival and inflammation in all cell types, results in multisystem dysfunction in the host. The inactivation of the MAPK pathway in both macrophages and dendritic cells leads to inhibition of proinflammatory cytokine secretion, downregulation of costimulatory molecules such as CD80 and CD86, and ineffective T cell priming. The net result is an impaired innate and adaptive immune response. Endothelial cells of the vascular system undergo apoptosis upon LT exposure, also likely due to inactivation of the MAPK pathway. The activity of various hormone receptors such as glucocorticoids, progesterone and estrogen is also blocked, due to inhibition of p38 MAPK phosphorylation, thus affecting the bodys response to stress. The present review summarizes the various disarming effects of Bacillus anthracis through the use of a single weapon, the lethal toxin.Received 12 June 2004; received after revision 13 July 2004; accepted 28 July 2004     

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.