The first highly stereoselective synthesis of digitoxin is described. It is a cardiotonic drug, which exhibits cardiac and anticancer properties. Unlike digoxin which is eliminated from the body via the kidneys, it is eliminated via the liver, so could be used in patients with poor or erratic kidney function. A direct comparison of the anticancer activities of digitoxin. For full access to this pdf, sign in to an existing account, or purchase an annual subscription. Stereochemical survey of digitoxin monosaccharides acs. Wilson and gisvolds textbook of organic medicinal and. Goldcatalyzed diversified synthesis of 3aminosugar. If cataclysmic event were to destroy all knowledge of science what would be the most important knowledge to pass on to future generations. A broad category of chemical compounds, also reffered as sugars. A list of us medications equivalent to digitoxin is available on the. Digoxin is taken by mouth or by injection into a vein common side effects include breast enlargement with other side effects generally due to an excessive dose.
Herein we present a chemical approach for the ready preparation of dsarmentosyl donors enabling the first total synthesis and structure validation of cardenolide n1, a challenging 2,6dideoxy3omethyl. The synthesis was based on a highly efficient goldcatalyzed glycosylation reaction with alkynylbenzoate 3aminoglycosides as glycosyl donors. Digoxin medicinal chemistry pharmaceutical sciences. Digitoxin is a medicine available in a number of countries worldwide. Grant program for the support of academic research in synthetic organic chemistry. Digitoxin and related cardenolides display potent anticancer activity against a range of human cancer cell lines in vitro but the clinical use of digitoxin to treat cancer has been restricted by its narrow therapeutic index. A cardiac glycoside extracted from the foxglove plant, digitalis lanata, it is used to control ventricular rate in atrial fibrillation and in the management of congestive heart failure with atrial fibrillation, but the margin between toxic and therapeutic doses is. A mild and atomeconomic rheniumvcatalyzed stereoselective synthesis of. Chemical access to dsarmentose units enables the total. B reckmann, crossreactivity of antidigoxin antibodies with digitoxin depends on tracer. Digitoxin natural products having a particular activity on the human body wich is benefic for the treatment of a particular disease. These drugs cause decrease in oxygen consumption or work load on heart.
It is used to control ventricular rate in atrial fibrillation and in the management of congestive heart failure with atrial fibrillation. Digoxin and digitoxin are the two principal cardiac glycosides. Foxgloves or purpureafoxgloves or purpurea growing in england cultivated in india roots, leaves, seeds contains several poisonous glycosides 2. Introduction 2 digoxin, which is extracted from digitalis lanata, is one of the cardiac glycosides, a closely related group of drugs having in common specific effects on the myocardium. From martindale, the extra pharmacopoeia, 30th ed, p665digitoxin inhibits the nakatpase membrane pump, resulting in an increase in intracellular.
About digoxin it is a purified cardiac glycoside extracted from the foxglove plant, digitalis lanata. Cardiac glycosides chemical structure and pharmacokinetics. Most frequently it is used for atrial fibrillation, atrial flutter, and heart failure. Digoxin is a cardenolide glycoside that is digitoxin betahydroxylated at c12. Digoxin, sold under the brand name lanoxin among others, is a medication used to treat various heart conditions. Various aspects of the solution conformation of the steroid. While digoxin was once regarded as the drug of choice for congestive heart failure with reduced left ventricular. The method has been successfully applied to a highly convergent synthesis of digitalis 2. Digitalis purpurea o ho oh o ho o o ho o o o oh o digitoxin digitoxin strongly stimulate the contraction of the heart. The analogues were tested for cytotoxicity against the nci panel of 60 human cancer cell lines and in more detail against nonsmall cell human lung cancer cells ncih460. Digitoxin is a lipid soluble cardiac glycoside that inhibits the plasma membrane sodium.
Digoxin is widely distributed and extensively bound in varying degrees to tissues throughout the body, which results in an apparent high volume of distribution. The techniques used include phasesensitive cosy, multiple relay cosy, and carbonproton correlation hetcor and hmqc spectra. A cardiac glycoside extracted from the foxglove plant, digitalis lanata, it is used to control ventricular rate in atrial fibrillation and in the management of congestive heart failure with atrial fibrillation, but the margin between toxic and therapeutic doses is small. Efficiency is the ratio of oxygen consumption to work done. Refer to the procedural notes section of this chemistry information sheet for information on unacceptable.
Its corresponding aglycone is digoxigenin, and its acetyl derivative is acetyldigoxin it is widely used in the treatment of various heart conditions namely atrial fibrillation. Chemical structure of digitoxin, c41h64o the molecule contains. Caution because this product is of human origin, it should be handled as though capable of transmitting infectious diseases. A direct comparison of the anticancer activities of. Department of chemistry emory university 1515 pierce drive atlanta, ga 30322, usa, fax. Digitoxin analogues with improved anticytomegalovirus activity. Digitoxin strongly stimulate the contraction of the heart. Generations of students and faculty have depended on this textbook not only for undergraduate courses in medicinal chemistry but also as a supple.
Cardiac glycosides are compounds isolated from plants and animals and have been known since ancient times. Determination of digoxin and digitoxin in whole blood. In addition, this method has been successfully applied to the synthesis of digitoxin trisaccharide glycal. The furyl derivative of digitoxigenin was coupled with one unit of digitoxose using our previously described acid catalyzed met. A growing body of evidence indicates that digitoxin cardiac glycoside is a promising. Its corresponding aglycone is digoxigenin, and its acetyl derivative is acetyldigoxin it is widely used in the treatment of various heart conditions namely atrial fibrillation, atrial flutter and sometimes heart failure th.
Quantitative determination of digitoxin and gitoxin in the leaves of digitalis purpurea. In addition, this method has been successfully applied to the synthesis of digitoxin trisaccharide glycal for the direct synthesis of digitoxin and c1. According to this strategy, a small library synthetic approaches to natural products via catalytic processes organic chemistry. In 1875, german chemist oswald schmiedeberg first isolated pure digitoxin from digitalis, leading others to extract and identify other glycosides from various species of digitalis. Common side effects include breast enlargement with other side effects generally due to an. From martindale, the extra pharmacopoeia, 30th ed, p665 digitoxin inhibits the nakatpase membrane pump, resulting in an increase in intracellular. Digoxin is taken by mouth or by injection into a vein. Quantitation of digitoxin, digoxin, and their metabolites. Drugs which increase the efficiency of heart are called cardiotonic drugs.
It is a cardiac glycoside sometimes used in place of digoxin. Introduction to chemistry, atoms and elements importance of chemistry question. These reagents are packaged specifically for use on a variety of au clinical chemistry systems. Application to the medicinal chemistry sarstudy of digitoxin authors. Us2449673a us691873a us69187346a us2449673a us 2449673 a us2449673 a us 2449673a us 691873 a us691873 a us 691873a us 69187346 a us69187346 a us 69187346a us 2449673 a us2449673 a us 2449673a authority us united states prior art keywords digitoxin water precipitate acetate digitalis prior art date 19460820 legal status the legal status is an assumption and is not a legal conclusion. It is a phytosteroid and is similar in structure and effects to digoxin though the effects are longerlasting. Oct 31, 2019 for most of the 1800s, digitalis was used to treat a wide variety of diseases and disorders. Jan 21, 2020 digitoxin and related cardenolides display potent anticancer activity against a range of human cancer cell lines in vitro but the clinical use of digitoxin to treat cancer has been restricted by its narrow therapeutic index.
The ld 50 value of digitoxin 163 in the mouse oral administration is 4950. The margin between toxic and therapeutic doses is small. Digitoxin and its analogs as novel cancer therapeutics cdc stacks. Oct 14, 2010 digitoxin is a cardiac glycoside currently being investigated for potential use in oncology. It is extracted form the leaves of digitalis lanta, digitalis orientalis, or scrophulariaceae 1016. Department of chemistry,west virginia university, morgantown, west virginia 26506, usa. Digoxin and digitoxin are therapeutically the most widely used digitalis glycosides. Digoxin drug information, uses, side effects, chemistry. Antidigoxin antibody fragments, the specific treatment for digoxin poisoning, biosynthesi also effective in serious digitoxin toxicity. Digitalis lanata and digitalis purpurea contains cardiac glycosides, volatile oil, fatty matter, starch. Digitalis lanata and digitalis purpurea of the family plantaginaceae were grown in iraq.
The heart glycosides, digoxin and digitoxin, are used to treat heart failure. Crossreactivity of antidigoxin antibodies with digitoxin. Digitoxin c41h64o cid 441207 structure, chemical names, physical and chemical. These compounds inhibit the activity of the sodium potassium pump in eukaryotic cells. Digitoxin was hydrolysed by the method of hasenfratz 1931. It is used from chronic cardiac insufficiency in decompensated valvular disease of the heart, myocardium overload in arterial hypertension, tachycardia, ventricular fibrillation, and other analogous situations. Department of chemistry and chemical biology, northeastern university, boston. A diversified synthesis of 3aminosugar analogues of digitoxin and digoxin with potent anticancer activities was explored. A list of us medications equivalent to digitoxin is available on the website. This study demonstrates the ability to improve the digitoxin anticancer activity by modification of the.
The emit 2000 digoxin assay is a homogeneous enzyme immunoassay intended for use in the quantitative analysis of digoxin in human serum or plasma. Digoxin exhibits strong systolic action and slows heart rate. Chemspider search and share chemistry for medical information relating to covid19, please consult the world health organisation or local healthcare provision. Cardiac glycosides cgs are a large family of chemical. It is used to treat congestive heart failure and cardiac arrhythmia.
Preface for 6 decades, wilson and gisvolds textbook of organic medicinal and pharmaceutical chemistry has been a standard in the literature of medicinal chemistry. Crossreactivity of antidigoxin antibodies with digitoxin depends on tracer structure r stenzel. Digitoxin is a cardiac glycoside currently being investigated for potential use in oncology. The 1 h and c nmr spectra of the cardenolides digitoxigenin, digoxigenin, digitoxin, and mono and bisdigitoxigenin digitoxosides have been completely assigned by twodimensional nmr spectroscopy. Department of agriculture, animal and health inspection service, denver wildlife research center, building 16. Structural studies of digitoxin and related cardenolides. Quantitative determination of digitoxin and gitoxin in.
Digoxin has positive inotropic and negative chronotropic activity. Stereoselective synthesis and glycosylation of the digoxin trisaccharide glycal frank e. Download scientific diagram chemical structure of digitoxin, c41h64o the molecule contains five oh groups. Sigmaaldrich offers a number of digitoxin products. Atomic theory is the central theme of chemistry and most important idea in science. On a new technology for obtaining digitoxin springerlink. Digoxin is made up of a molecule of digoxigenin and three molecules of digitoxose. Sessions valencia college chm 2211c digitoxin from smith organic chemistry with biological topics ch 21 aldehydes and ketones key. Quantitation of digitoxin, digoxin, and their metabolites by highperformance liquid chromatography using pulsed amperometric detection kevin l. Introduction to natural products and medicinal chemistry. Strophanthus gratus ouabain an account of the foxglove and some of its medicinal uses.
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