A STUDY ON THE STRUCTURE-ACTIVITY RELATIONSHIP OF THE CARDIOTONIC STEROIDS.
According to the prevailing opinion of today about the structure-activity relationship of cardenolides and bufadienolides, the structural requirements for the characteristic cardiotonic action of these compounds can be summarized as follows: cis-fusion of the C and D rings, hydroxyl groups in positions 3β and 14β, and a five- or six-membered unsaturated lactone ring having β-configuration at C14 (1). Most of the experimental data referred to as evidences supporting this opinion have come, however, from the determination of toxic doses in the whole animal, mainly in the cat, rather than from observations of the action of these compounds in isolated hearts. It follows as a natural consequence that the compounds with a rather weak toxicity have been condemned to be inactive, even if they have a strong cardiotonic action, in spite of the fact that such a kind of compounds may actually be more important from the clinical point of view. For example, the compound like dihydrodigitoxin of which the lactone ring is saturated, and the compound like resibufogenin, which have an epoxide ring between C14 and C15 instead of C14-OH, generally believed to be inactive based on the toxicity data in the cat, have recently been found to be fairly active when tested in the isolated heart (2-3). The authors also found that, different from the above-cited opinion, the presence of 3β-OH is not indispensable for the cardiotonic action of the cardenolides ; 3-epi-digitoxigenin was found to have a definite cardiotonic action upon the isolated frog's heart (See Fig. 8). These findings seem to warrant reexamination of the problem, on the basis of the action of these compounds in the isolated heart. In recent years several adrenocortical steroids and aldosterone antagonists have been reported to be cardiotonic (4-6), despite the fact that their stereochemical structures are essentially different from those of the cardiotonic steroids. In view of these, the authors took up the problem of the cis-fusion of the C and D rings out of the several important points in the structure of cardiotonic steroids as discussed above and reexamined its importance for the specific cardiotonic action using the isolated frog's heart and the heart-lung preparation of the dog.
Neotanghiferin. Glykoside und Aglykone, 164. Mitteilung
Tanghiferin erwies sich als isomorphe Mischung (evtl. molekulare Verbindung) von ungefahr gleichen Teilen Tanghinin und eines weiteren Stoffes, der Neotanghiferin genannt wurde. Die Trennung gelang durch praparative Papierchromatographie. Neotanghiferin und Desacetyl-tanghiferin zeigten an der Katze und am Frosch keine digitalisartige Wirkung. Tanghiferigenin, das Aglykon des Neotanghiferins, enthalt nur eine (wahrscheinlich sekundare) HO-Gruppe und vermutlich eine hexacyclische Ketogruppe. Zwei weitere Sauerstoff- atome durften in einem Butenolidring enthalten sein, dessen Doppel- bindung aber vermutlich keinen weiteren Substituenten tragt. Die bisherigen, allerdings nur vorlaufigen Resultate sprechen dafar, dass Tanghiferigenin nicht das normale Cardenolid-Gerust enthalt.
Identification of Dihydroxy Aromatic Compounds in a Low-Temperature Pyrolysis Coal Tar by Gas Chromatography−Mass Spectrometry (GC−MS) and Fourier Transform Ion Cyclotron Resonance Mass Spectrometry (FT-ICR MS)
Dihydroxy aromatics in coal tar undergo rapid coupling reactions with each other and with some coal-derived species during coal pyrolysis and liquefaction. However, only limited information on the structure of dihydroxy aromatics is known. In this study, Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) and gas chromatography−mass spectrometry (GC−MS) were used to characterize the dihydroxy aromatics in a low-temperature pyrolyzed coal tar and its distillate and residue fractions. Negative-ion electrospray ionization (ESI) FT-ICR MS spectra of coal-tar-derived samples had low molecular masses and narrow mass ranges. Negative-ion ESI is extremely selective for the dihydroxy aromatics present in coal tar. The O2 class species had the highest ion intensity among the species in the negative-ion FT-ICR mass spectrum for each sample. Dihydroxy compounds with an aromatic core structure of benzene, indan, biphenyl (and/or acenaphthene), and naphthalene were identified in the distillate fract...