Bufadienolides from Urginea maritima from Egypt.

Forty-one bufadienolides were isolated from the bulbs of Urginea maritima agg. from Egypt; 26 of them are new natural compounds. Structure elucidation was performed by comparison with authentic substances or by means of 1H, 13C NMR and FAB mass spectroscopy. Sixteen of the glycosides derive from nine structurally new aglycones: 16 beta-hydroxy-scillarenin, 16 beta-O-acetyl- scillarenin, 12 beta-hydroxy-5 alpha-4,5-dihydro-scillirosidin, 16 beta- hydroxy-5 alpha-4,5-dihydro-scillirosidin, 16 beta-O-acetyl-5 alpha-4,5- dihydro-scillirosidin, 12 beta-hydroxy-scillirubrosidin, 16 beta-O-acetyl- scillirubrosidin, 9-hydroxy-scilliphaeosidine and 12 beta-hydroxy-desacetyl- scillirosidine.

Guaianolide-endoperoxide and monoterpene-hydroperoxides from Achillea nobilis.

From flower heads of Achillea nobilis two chrysanthemol derivatives (1, 2), tanaparthin-beta-peroxide (3), and 5-hydroxy-3,6,7,4'-tetramethoxyflavone (4) were isolated by repeated column chromatography and HPLC. Structure elucidation has been performed by means of MS, 1H-NMR, 13C-NMR, and 2D-NMR experiments.

About the bufadienolide complex of "red" squill.

Red coloured bulbs of plants of the URGINEA MARITIMA aggregate from the northern and southern Mediterranean area were shown to exhibit different bufadienolide compositions. Therefore, the bufadienolide complex of "red squill" samples from Tunesia and from Sardegna was investigated. Twelve bufadienolides were isolated from bulbs of tetraploid squill from Tunesia, sixteen from tetraploid samples from Sardegna. The Compounds were identified by means of FAB-MS, (1)H-NMR, and (13)C-NMR studies or comparison with authentic substances. Both of the samples contained scilliroside ( 14), scillarenin 3- O-beta- D-glucoside ( 2), proscillaridin A (1), scilliphaeosidin 3- O-beta- D-glucoside ( 5), scilliglaucoside ( 17), scilliphaeoside ( 4), and 12- EPI-scilliphaeoside ( 7); the bulbs from Tunesia contained additionally glucoscilliphaeoside ( 6) and the four new bufadienolides 12- EPI-glucoscilliphaeoside ( 10), 12beta-hydroxyscilliglaucosidin 3- O-beta- D-glucoside ( 21), 12- EPI-scilliphaeosidin 3- O-beta- D-glucoside ( 8), and 12- EPI-scilliphaeosidin 3- O-alpha- L-rhamnosido-alpha- L-rhamnoside ( 9). In the bulbs from Sardegna scülaren A ( 3), gamabufotalin 3- O-alpha- L-rhamnoside ( 20), scilliglaucoside ( 17), scillirubrosidin 3- O-alpha- L-rhamnoside ( 11), scillirubroside ( 12), 12beta-hydroxyscilliroside ( 15), 5alpha-4,5-dihydroscillirosidin 3- O-alpha- L-thevetosido-beta- D-glucoside ( 19), and deacetyl-scilliroside ( 8) besides the new Compounds 10-carb-oxy-5beta,14beta-dihydroxybufa-3,20,22-trienolide 5- O-beta- D-glucoside ( 18) and scilliglaucogenin ( 16) were found in addition. Not only quantitative but even qualitative differences in the bufadienolide pattern between the samples of the northern and the southern Mediterranean area were proved. By now it is not clear whether the investigated samples belong to different chemodemes of URGINEA NUMIDICA or are two different species of the URGINEA MARITIMA aggregate.

Bufadienolides from Urginea maritima sensu strictu.

Fourteen bufadienolides were isolated from bulbs of hexaploid URGINEA MARITIMA (L.) Baker SENSU STRICTU. The compounds were identified by means of FAB-MS, (1)-NMR and (13)C-NMR studies or comparison with authentic substances. Besides the already known proscillaridin A, scillaren A, glucoscillaren A, scilliphaeoside, glucoscilliphaeoside, 12- EPI-scilliphaeoside, gamabufotalin-3- O-alpha- L-rhamnoside, 16beta- O-acetyl-gamabufotalin-3- O-alpha- L-rhamnoside, scilliglaucoside, and scillicyanoside, four new bufadienolides were isolated: 5alpha-4,5-dihydroproscillaridin A, 5alpha-4,5-dihydroglucoscillaren A, gamabufotalin-3- O-alpha- L-rhamnosido-beta- D-glucoside, and 19-oxo-5alpha-4,5-dihydro-proscillaridin A.

Bufadienolides from Urginea pancration.

From bulbs of URGINEA PANCRATION (Steinh.) G. de Philippe (Hyacinthaceae) 5 bufadienolides were isolated by a combination of column and droplet counter-current chromatography; their structures were elucidated mainly by FAB-MS and (1)H- and (13)C-NMR spectroscopy. Besides the already known scilliglaucoside ( 1), scillirubroside ( 2), and scilliroside ( 3), two new bufadienolides were identified: 5alpha-4,5-dihydroscillirosidin- 3beta- O-alpha- L-thevetosido-4'-beta- D-glucopyranoside and arenobufagin-3beta- O- L-rhamnopyranosido-4'-beta- D-glucopyranoside.

Cardenolides from Ornithogalum boucheanum.

From leaves and bulbs of ORNITHOGALUM BOUCHEANUM (Kunth) Aschers. et Graebn. (Liliaceae), cardenolides were isolated by a combination of column and droplet counter-current chromatography. Their structure elucidation was performed mainly by means of (1)H-NMR, (13)C-NMR, EI-MS, and LD-MS studies as well as by acid and/or enzymatic hydrolysis of the glycosides followed by identification of genins and sugar moieties (TLC, GC). Eight cardenolides were identified as sarmentogenin-3- O-6'-deoxy-beta- D-allosido-beta- D-xylosido-alpha-L-rhamnoside, sarmentogenin-3- O-6'-deoxy-beta- D-allosido-beta- D-xylosido-beta- D-apioside, 15beta, 16alpha-dihydroxyuzarigenin-3- O-beta- D-digitoxosido-beta- D-xylosido-alpha- L-rhamnoside, sarmentogenin-3- O-beta- D-digitoxosido-beta- D-xylosido-beta- D-apioside, syriogenin-3- O-beta- D-digitoxosido-beta- D-xylosido-alpha- L-rhamnoside, sarmentogenin-3- O-alpha- L-rhamnosido-beta- D-apioside, uzarigenin-3- O-beta- D-digitoxosido-beta- D-xylosido-alpha- L-rhamnoside, and digitoxigenin-3- O-6'-deoxy-beta- D-allosido-beta- D-xyloside. This is the first report of the occurrence of 15beta, 16alpha-dihydroxyuzarigenin. The presence of three genins - syriogenin, uzarigenin, and digitoxigenin - in the genus ORNITHOGALUM is described for the first time. For cardenolides, not only the combination of three different monosaccharides in one glycoside is unusual, but, especially, the occurrence of apiose, which was not known for cardiac glycosides until now.

Structure of the toxic domain of the Escherichia coli heat-stable enterotoxin ST I.

Active fragments of the heat-stable enterotoxin ST I of Escherichia coli were chemically synthesized with the sequence Cys-Cys-Glu-Leu-Cys-Cys-Asn-Pro-Ala-Cys-Thr-Gly-Cys-(Tyr) and studied by proton (1H NMR) and carbon-13 (13C NMR) nuclear magnetic resonance spectroscopy as a function of pH and temperature. All of the nonexchangeable protons in the 1H NMR spectrum were assigned. Although all amide protons were present at temperatures below 25 degrees C and and pH values below 6, some of the resonances are broad and could not be assigned. The temperature dependence of these broad resonances indicates a change in conformation that is localized in the N-terminus. Other amide protons disappear at higher temperatures owing to chemical exchange with the solvent. Sufficient resonance assignments can be made at high and low temperatures to permit structural conclusions to be made. The chemical shifts of the alpha-carbon protons indicate the presence of substantial structure, which was further defined with the observed pattern of nuclear Overhauser enhancements (NOEs), coupling constants, and exchange rates. The NMR data identify a turn from Ala-14 to Cys-18. A second likely turn is centered around the proline residue. An interresidue NOE between the alpha-carbon protons of Asn-12 and Gly-17 indicates that the molecule folds back on itself. The NMR information is sufficient to define the structure of the C-terminal region of ST I. Manual model building then indicated that one arrangement of the three disulfides is particularly compatible with the NMR data and van der Waals constraints. A model incorporating the disulfide arrangement proposed by Houghten and his co-workers [Houghten, R.A., Ostresh, J.M., & Klipstein, F.A. (1984) Eur. J. Biochem. 145, 157-162] and the NMR constraints was derived with the programs PROTO [Frayman, F. (1985) Ph.D. Thesis, Northwestern University] and NOEMOT [Lane, A.N., Lefévre, J.-F., & Jardetsky, O. (1986) Biochim. Biophys. Acta 867, 45-56].

Synthesis of radioiodinated metyrapone--a potential adrenal imaging agent.

Metyrapone has been labelled with radioiodine selectively in the 4'-position of ring B. The synthesis of 123I-(131)-metyrapone involves four intermediate compounds. 4'-Bromo-metyrapone serves as a stable precursor that is labelled before use. Studies of the biodistribution of [131I]metyrapone in rats indicate the highest concentration in the adrenal gland 10 min after the injection with a fast elimination of the radioactivity. However, the absolute uptake in the normal adrenal is low. When [123I]metyrapone was used in a patient with bilateral hyperplasia, faint adrenal images were obtained.