Butenolide Ring Research Articles

Polynitro Aromatic Compounds in Analytical Chemistry I: Reaction with Ouabain and Digitoxin

By the use of NMR spectroscopy, the highly colored reaction products formed by ouabain or digitoxin with 1,3,5-trinitrobenzene or 2,4,6-trinitroanisole in the presence of alkali (as used for the determination of these glycosides) are shown to be Meisenheimer complexes. The complexes are produced by attachment of a carbon of the butenolide ring to an aromatic carbon of the nitro compound with formation of a charge-delocalized cyclohexadienate anion.

Partition high-pressure liquid-chromatographic systems for the separation of digitalis glycosides of the cardenolide group

Several multi-component liquid-liquid systems have been investigated on silica gel SI-60 supports of particle size 10 μm. By using two solvent systems, it was possible to separate 14 digitalis glycosides, ranging from genins of relatively low polarity to the highly polar deacetyl-lanatosides. Solvents with good ultraviolet transparency at 220 nm (λmax, for the butenolide ring) were chosen in order to improve the sensitivity of detection. The technique should also permit the determination of by-products and degradation products of these drug substances. Detection limits are as low as 15 ng for a 5-μl injection, and separation times vary between 4 and 20 min. The reproducibility of the retention times and the baseline separations attainable make the systems suitable for quantitative work.

Cardiotonic Steroids II: 3-Deoxycardenolides and 3-Deoxycardanolides

A series of compounds related to 3‐deoxydigitoxigenin was prepared and assayed for inhibition of myocardial Na+, K+‐adenosine triphosphatase. Although the relatively high activity of 3‐deoxydigitoxin was confirmed, the corresponding 3β, 4β‐epoxide and a mixture of 2, 3‐olefins and 3, 4‐olefins were less active. 3‐Deoxy compounds with variations at the 14‐position and the butenolide ring were much less active than the corresponding 3β‐hydroxy analogs. Thus the activity of 3‐deoxydigitoxigenin appears to be particularly susceptible to structural changes elsewhere in the molecule.

The replacement of the hydrogen atoms of the CH2 group of the butenolide ring of a cardenolide by deuterium

It has been shown by the NMR-spectroscopic method that when cardenolides are treated with CD3OD no deuterium exchange of the protons of the CH2 group of the butenolide ring takes place. The entry of the label into this position takes place in the mass spectrometer.

Mechanismus der basenkatalysierten reaktion von Cardenoliden—I: Abhängigkeit vom Lösungsmittel

The mechanism of base-catalysed isomerization of cardenolides, using mainly 17α-digitoxigenin ( 1) and digitoxigenin ( 10) as test compounds, has been studied by means of kinetic analyses. The solvent used is shown to determine decisively reaction course and speed of isomerization. In aqueous potassium hydroxide solution, the attack of the OH ion primarily effects the hydrolysis of the butenolide ring to furnish the α,β-unsaturated γ-hydroxycarbonic acids 2 or 11. In these compounds the double bond is shifted very slowly to β,γ-position, yielding by rearrangement of the aldenols 7 or 12 the γ-aldehyde carbonic acids 3 or 13 as isomerization products, which, on neutralization, are in equilibrium with the cyclic semiacylate 4 or the cyclic semiacetal 16. In absolute methanolic potassium hydroxide solution, the attack of the more basic methoxylate ion effects the formation of the furyl anions 8 or 14. This is shown to be the rate-limiting step of isomerization, accelerated by additional OH groups in 12β-, 16α- or 16β- position of 10. 8 adds methanol to yield methoxy lactone 5. However, 14 by an intramolecular addition of the 14β-OH group to the furyl ring forms 14,21-epoxide 15. In aqueous methanolic potassium hydroxide solution, both initial hydrolysis of the cardenolides 1 or 10 and hydrolysis of the isomerization products 5 or 15 competitively take place, yielding the γ-aldehyde carbonic acids 3 or 13.

Reaction of 3-0-acetyl-14-anhydrodigitoxigenia and 3-0-acetyldigitoxigenin with osmium tetroxide

AbstractTreatment of 3‐O‐acetyl‐14‐anhydrodigitoxigenin (1) with 1.1 equivalents of OsO4 gave both the 14α, 15α‐diol 2 and the 14β, 15β‐diol 4. Degradation to the corresponding methyl etianates 7 and 10, respectively, established their stereochemistry. Treatment of both the 14‐hydroxy‐15‐acetoxy‐cardenolides 3 and 5 with OsO4 leads to the expected mixtures of 20, 22‐diols, a partial separation of which was achieved after acetylation. The butenolide ring of 3‐O‐acetyl‐digitoxigenin (25) also reacted with OsO4, yielding the two 20,22diols 26 and 27, the stereochemistry of which has tentatively been assigned on the basis of NMR. data.

Mass spectra of α,β‐substituted butenolides

AbstractThe mass spectra of twenty‐six β‐ and α,β‐substituted butenolides have been examined. Fragmentation of the butenolide ring can be rationalised on the basis of the fragmentation pathways described for β‐hydroxybutenolides. However, a number of butenolides, e.g. the α‐(substituted)benzamido‐β‐hydroxymethyl‐butenolides, show a weak fragmentation of the ring. The fragmentations in which the substituents are involved are more favourable and interactions between the substituents on the α‐ and β‐positions complicate these spectra.

NMR spectra of cardenolides with an oxygen-containing function at C10

The NMR spectra of 12 cardenolides with oxygen-containing functions at C10 has been studied. The chemical shifts of the signals of the protons of the C18 angular methyl group, a butenolide ring, and some other protons have been discussed as functions of the structural features of the individual compounds.

Butenolidringspezifische, quantitative papier- und dünnschichtchromatographie von Cardenolidglykosiden (Digitoxin) mit 2,4,2′,4′-Tetranitrodiphenyl

A butenolide ring specific method of quantitative paper and thin-layer chromatographic analysis of cardenolides and cardenolide glycosides using 2,4,2′,4′-tetranitrodiphenyl is described. According to their molar extinction coefficients, εmax 22 600 (PC/digitoxin) and 21 500 (TLC/digitoxin) resp., they show high detection sensibility.

Reaction of the lactone ring of diffugenin

Under the influence of caustic alkalies, diffugenin (14-anhydrostrophanthidin) undergoes a complex irreversible change with the opening of the butenolide ring. The main product is a γ-hydroxy-γ-lactone (lactol)-the stable tautomeric form of a γ-aldehydo acid. The existence of aldo-lactol tautomerism is confirmed by the preparation of derivatives of the α and Ω forms. The hypothesis has been put forward that the double bond at C14 in diffugenin and its derivatives readily undergoes autoxidation with the formation of epoxy compounds.

Optical rotary dispersion and configuration in cardenolides

AbstractIn accordance with the results of Weiss & ZIFFER, the ORD spectra of cardenolides with few exceptions show a distinct Cotton effect, caused by the butenolide ring. The two extrema lie at about 260 and 228 nm; the extremum at shorter wave length is very difficult to measure, and that at longer wavelength shows fine structure in dioxane. 14α,17β‐cardenolides having either a hydrogen atom or a hydroxyl group at C‐14 and no double bond in rings C and D show a negative Cotton effect, whereas compounds of the other three stereoisomeric types (14α,17α; 14β,17α and 14β,17β) show a positive Cotton effect. In the case of cardenolides having an oxo group, the extremum of the oxo group at shorter wavelength overlaps that of the butenolide ring at longer wavelength. In spite of this the latter extremum could still be seen distinctly in all cases investigated to date.

BIOSYNTHESIS OF PLANT STEROIDS. I. THE ORIGIN OF THE BUTENOLIDE RING OF DIGITOXIGENIN.

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTBiosynthesis of Plant Steroids. I. The Origin of the Butenolide Ring of Digitoxigenin1Edward Leete, Harry Gregory, and Eduardo G. GrosCite this: J. Am. Chem. Soc. 1965, 87, 15, 3475–3479Publication Date (Print):August 1, 1965Publication History Published online1 May 2002Published inissue 1 August 1965https://doi.org/10.1021/ja01093a034RIGHTS & PERMISSIONSArticle Views246Altmetric-Citations40LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (588 KB) Get e-Alerts Get e-Alerts

Die Biosynthese des Digitoxigenins, Herkunft des C‐20. Glykoside und Aglykone, 253. Mitteilung

AbstractMevalonic‐[3‐14C] acid (Ia) has been prepared by partial reduction of β‐hydroxy‐β‐methyl‐glutari‐[3‐14C] acid. After introduction of the ammonium salt of Ia into Digitalis lanata plants by the vick technique, crist. radioactive digitoxigenin was isolated. This contained a significant amount of radioactivity in C‐20 position. From this, together with results of former authors, it follows that the biosynthesis of digitoxigenin from mevalonic acid (probably via squalene) proceeds through a pregnane derivative. The latter needs only one molecule of acetate to form the butenolide ring.