Untersuchungen zur Eiweißbindung von Arzneistoffen durch kontinuierliche Ultrafiltration, 3. Mitt.5) Eiweißbindung von blutgerinnungshemmenden Tetronsäuren

Protein Binding of Drugs Determined by Continuous Ultrafiltration, III: Protein Binding of Anticoagulant Tetronic Acids The binding of five anticoagulant tetronic acids to human serum albumin has been determined by continuous ultrafiltration. The most active compounds show the strongest binding. Compound 5 is bound as strongly as phenprocoumon. In spite of their strong binding, the tetronic acids investigated exhibit a quick onset and a short duration of their anticoagulant activity.     

Untersuchungen zur Eiweißbindung durch kontinuierliche Ultrafiltration, 2. Mitt. Eiweißbindung von Warfarin

Protein Binding of Drugs Determined by Continuous Ultrafiltration, II: Protein Binding of Warfarin The binding of warfarin to human serum albumin has been investigated in the ranges (c_total) of 0.6–4.2 μg · ml^?1 (fluorescence detection) and 100–400 μg · ml^?1 (ultraviolet detection). The amount of unbound drug is 0.5% and nearly constant up to 100 μg · ml^?1. The other parameters, too, correspond fairly well to those obtained with other methods. There is no significant difference between the binding parameters of warfarin and phenprocoumon in therapeutically achieved concentrations.     

Untersuchungen zur Eiweißbindung von Arzneistoffen durch kontinuierliche Ultrafiltration, 5. Mitt. Einfluß der S-Oxidation auf die Proteinbindung von Methylthioderivaten des Warfarins

Protein Binding of Drugs Determined by Continuous Ultrafiltration, V: Effect of S-Oxidation on the Protein Binding of Methylthio Derivatives of Warfarin The binding of three methylthio derivatives of warfarin to human serum albumin has been determined by continuous ultrafiltration. 4′-(Methylthio)warfarin S-oxide (2) has a free fraction that is seven to nine times as large as that of warfarin itself in the therapeutically used plasma concentrations (2.5–12.5 μmol/l). As 2 is effective in the same dose as warfarin and shows better pharmacokinetics it might improve the safety of oral anticoagulants.     

Untersuchungen an 1, 4-Naphthochinonen, 17. Mitt.: Untersuchungen zur Synthese von 3-Hydroxyjuglonderivaten

1, 4-Naphthoquinones, XVII: Studies on the Synthesis of 3-Hydroxyjuglone Derivatives Contrary to 3-chlorojuglone ( 1 ) the isomeric 2-chloro derivative 2 is a suitable compound for the synthesis of 2-methoxy- [ 6 ] and 2-hydroxyjuglone in CH₃OH/OH. In DMSO-CH₃O^? the results are inverse but the yield (50%) of 3-methoxyjuglone ( 5 ) is only moderate. The best method for the preparation of this key compound is acid catalyzed addition of CH₃OH to juglone followed by Fe (III)-oxidation.     

Diindolylmethane, 5. Mitt. Chlorwasserstoffkatalysierte Kondensation von Yohimbin mit 4-Dimethylaminobenzaldehyd — Untersuchungen zur Yohimbin-Farbreaktion

Hydrogen Chloride Catalysed Condensation of Yohimbine with 4-Dimethylaminobenzaldehyde — Investigations of the Yohimbine Color Reaction Yohimbine (1) reacts with 4-dimethylaminobenzaldehyde (2) in the presence of hydrogenchloride/methanol to give the isomeric diindolymethanes 4 via the methylbenzhydryl ethers 3 which can be isolated. The structures of compounds 3 and 4 were determined by ¹H-NMRspectroscopy. In the acidcatalysed color reaction of 1 with 2 the diindolylmethane 4 might be an intermediate.     

Photochemische Studien, 52. Mitt.: Untersuchungen zur Photostabilität von Testosteron und Methyltestosteron im kristallinen Zustand

Photochemical Studies LII: Investigation on the Photostability of Testosterone and Methyltestosterone in the Solid State Irradiation of testosterone in the solid state yields 4-androstene-3,17-dione and 5α-androstane-3,17-dione, while that of methyltestosterone leads to 17-methyl-13,17-seco-androst-4-ene-3,17-dione. For these light-induced transformations disproportionations are proposed as mechanism.     

Untersuchungen an 1,3-Thiazinen, 33. Mitt.1) Oxidationen an Thiourethanen, 7. Mitt.2). Oxidative Desulfurierung von Dithiourethanen durch salpetrige Säure und Salpetersäure

1,3-Thiazines, XXXIII¹⁾; Oxidations of Carbamothioates, VII²⁾: Oxidative Desulfurisation of Carbamodithioates by Nitrous and Nitric Acid Carbamodithioates, mainly 2-thioxo-tetrahydro-4H-1,3-thiazin-4-ones 1 , were converted to carbamothioates, mainly 5,6-dihydro-2H-1,3-thiazin-2,4(3H)-diones 2 , by nitrous and nitric acid. With cone. nitric acid additional nitration of phenyl substituents was achieved.     

Heterocyclen durch Michael-Reaktionen, 8. Mitt. Reaktionen von Hydroxymethylentetralon mit Cyanessigsäurederivaten

Heterocycles by Michael Reactions, VIII¹: Reactions of (Hydroxymethylene)tetralone with Derivatives of Cyanoacetic Acid . (Hydroxymethylene)tetralone 1 does not react with derivatives of cyanoacetic acid in a ratio 1:1 like other 1,3-dicarbonyl compounds but in a ratio 1:2. These reactions yield compounds 10 and 17 , whoses structures were elucidated mainly by spectroscopic methods. A reaction path is proposed.     

Untersuchungen über Inhaltsstoffe von Lippia americana, 2. Mitt.

Isolation and Structure of Substances in Lippia Americana, II Free fatty acids, carbohydrates, fatty acids of waxes, alcohols of waxes, amino acids and choline were determined qualitatively and quantitatively.     

Beiträge zur Extraktion von Drogen. 4. Mitt.: Selektive Extraktionseigenschaften von Lösungsmitteln

Extraction of Vegetable Drugs With the squill as example it is shown that the components of the extractable matter can be extracted selectively up to a certain point in a fractioned extraction with solvents of increasing polarity.     

Dihydroisochinolinumlagerung, 26. Mitt. Untersuchungen der Stereochemie durch chiroptische Verfahren

Dihydroisoquinoline Rearrangement, XXVI: Investigation of the Stereochemistry by Chiroptical Methods The rearrangement of (+) 1 leads to (-) 2 as the product. By chemical correlation it was shown that both compounds possess S-configuration. This result was confirmed by chiroptical methods.     

Untersuchungen zur Isolierung von Flavonoiden mit Hilfe der Oxide und Salze zweiwertiger Kationen, 4. Mitt. Die Isolierung von Flavonoid-Glykosiden aus Drogen

Isolation of Flavonoids Using Oxides and Salts of Bivalent Cations, IV: The Isolation of Flavonoid Glycosides from Drugs The isolation of flavonoid glycosides by sorption onto MgO is described. Extracts from drugs containing large quantities of tannins must be freed from the tannins using ethylacetate precipitation or gel filtration. The isolation of flavonoid aglycones, flavonoid glycosides and the total flavonoids from plant material is demonstrated.     

Zur NMR-Spektroskopie von Strylalkyloximen. 4. Mitt. zur Dünnschichtchromatographie ungesättigter Oxime

Isomeric styryl alkyl oximes were separated by thin-layer chromatography and studied by NMR-spectroscopy. The vinyl protons of the α-isomers consist of only one peak at 6,81–6,90 ppm, those of the β-isomers are not equivalent (AB-spectrum). By this difference of the vinyl protons, mixtures of isomeric α-and β-oximes may be analysed and the configuration of unknown oximes determined.     

Untersuchungen an 1,3-Dicarbonyl-verbindungen, 4. Mitt.: Reaktionen von β-Keto-nitrilen

Reactions of β-Keto-nitriles . Dieckmann-condensation of the nitriles 1c and 4 gives the heterocyclic β-keto-nitriles 2b and 2d , while the amide 13 , obtained from 4 , cyclisizes to the imidazo[1,2-a]quinoline-2,5-dione 15 . The structures of the products from the β-keto-nitriles 2 with thiophenol, amines, alcohols or conc. H₂SO₄ are proved by spectroscopic methods.     

Untersuchungen an 1.3-Thiazinen, 34. Mitt. Oxidationen an Thiourethanen, 8. Mitt. Oxidative Desulfurierung und nitrosierende N-Desalkylierung durch salpetrige Säure oder Salpetersäure

1.3-Thiazines, XXXIV; Oxidations of Thiourethanes, VIII Oxidative Desulfurisation and Nitrosating N-Dealkylation by Nitrous or Nitric Acid Depending on the reaction conditions, 3-amino-2-thioxotetrahydro-4H-1.3-thiazin-4-ones 1 are desulfurized by nitrous or nitric acid to yield the 2-oxoanalogues 2 or in addition are dealkylated at the nitrogen atom with liberation of aldehydes and subsequent N-nitrosation to 3 .