Natural Cardenolides Research Articles

ChemInform Abstract: UEBER DEN ERSATZ DES RINGSAUERSTOFFS IM LACTONRING DER CARDENOLIDE DURCH STICKSTOFF

Chemischer InformationsdienstVolume 10, Issue 44 Natural Products ChemInform Abstract: UEBER DEN ERSATZ DES RINGSAUERSTOFFS IM LACTONRING DER CARDENOLIDE DURCH STICKSTOFF R. MEGGES, R. MEGGESSearch for more papers by this authorH. J. PORTIUS, H. J. PORTIUSSearch for more papers by this authorK. R. H. REPKE, K. R. H. REPKESearch for more papers by this author R. MEGGES, R. MEGGESSearch for more papers by this authorH. J. PORTIUS, H. J. PORTIUSSearch for more papers by this authorK. R. H. REPKE, K. R. H. REPKESearch for more papers by this author First published: October 30, 1979 https://doi.org/10.1002/chin.197944327AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume10, Issue44October 30, 1979 RelatedInformation

Inhibition of heart and brain cvclic adenosine 3′,5′-monophosphate phosphodiesterase by new non-steroidic compounds structurally related to natural cardenolides

AP 10 and related compounds are non-steroidic analogs of cardenolides which exhibit cardiotonic effects on mammals and amphibians isolated hearts. These synthetic compounds were effective inhibitors of the high affinity cyclic AMP phosphodiesterase of beef heart, rat heart and rat brain. AP 10 was the best inhibitor among them. It was approximately ten times as potent as theophylline and three times less effective than MIX and papaverine. Its affinity for the heart enzyme was eight to ten times higher than for the brain enzyme. The inhibition produced by AP 10 was competitive, reversible and was not reversed by high concentrations of magnesium ions. AP 10 slightly affected the binding of cyclic AMP with specific binding protein, but it had a far lower affinity for the binding sites than cyclic AMP. The possibility that inhibition of the low K m phosphodiesterase by AP 10 and related compounds may contribute to their cardiotonic action is discussed.

Studies on the synthesis of cardiotonic steroids. I. Efficient synthesis of cardenolides.

Practical synthetic methods of natural cardenolides are illustrated in the syntheses of xysmalogenin and digitoxigenin. The new routes employ pregn-14-en-20-one as key intermediate which was prepared by partial reduction of 14, 16-dien-20-one with triphenylstannane or triethylsilane. A general and efficient method was devised for obtaining cardenolides consisting of (1) 21-methylsulfenylation of pregnen-20-one, (2) the reaction of the resulting 21-methylthio derivative with bromoacetate and zinc, (3) alumina chromatography of epoxy ester obtained from the S-methylated Reformatsky product.

Conversion of digoxigenin to 5alpha-digoxigenin: structure of syriogenin.

3-Oxo-12β, 14-dihydroxy-14β-carda-4, 20(22)-dienolide (VII) derivable from digoxigenin (V) was treated with lithium borohydride in pyridine to give 5α-digoxigenin (VIa), which was demonstrated to be identical with the natural cardenolide aglycone, syriogenin. The structure of syriogenin was thus firmly established as 3β, 12β, 14-trihydroxy-5α, 14β-card-20(22)-enolide.