Cardiac glycosides structure

K. Repke (1985). New developments in cardiac glycoside structure-activity relationships. Trends Pharmacol. Sci. 6 275-278. 

FIGURE 10.12 The structures of several cardiac glycosides. The lactose rings are yellow. 

Cardiac Glycosides. Figure 2 Cardiac glycosides - molecular structure of digoxin and ouabain. Digoxin contains an additional hydroxy group in position 12 compared to digitoxin. 

This process starts with the synthesis of novel chemical compounds. Substances with complex structures may be obtained from various sources, e.g., plants (cardiac glycosides), animal tissues (heparin), microbial cultures (penicillin G), or human cells (urokinase), or by means of gene technology (human insu-Un). As more insight is gained into structure-activity relationships, the search for new agents becomes more clearly focused. 

The carbohydrate part of various cardiac glycosides can be mono-, di-, tri-, and tetrasaccharide, and the aglycon (genin) is a steroid with certain unique structural characteristics. The main purpose of sugar residues is evidently to facilitate solubility of... 

Natural products are generally classified by a number of criteria functional, structural and biosynthetic. Despite the reservations expressed above, certain functional subdivisions are useful in certain applications. Such terms as antibiotics, hormones or cardiac glycosides are commonly used. The grouping of natural products on the basis of common carbon skeletons is perhaps the most attractive for the chemist. The realization that many natural products fall into distinct structural groups which could be, at least formally, derived from much simpler molecules was an important development in that it led to the proposal of speculative biogenetic hypotheses which were largely responsible for stimulating the rapid development of the field of biosynthesis. However, such an approach is not entirely satisfactory since it is now clear that many compounds which are of similar structural types are derived by quite different routes in vivo. 

In recent years the chemistry of 2-desoxysugars generally, has been considerably broadened. In particular, new methods of synthesis have been developed for the preparation of many of the didesoxysugars known as the 2-desoxyhexomethyloses which occur naturally as components of the cardiac glycosides. The formation, structure, and stability of various 0- and iV-glycosides of sugars of this class have been examined in... 

Oxidation with Potassium Permanganate.—Oxidation with potassium permanganate of 2- and 3-desoxyhexose monomethyl ethers, obtained from the cardiac glycosides or by synthesis, has been employed extensively by Reichstein and his colleagues, since valuable information on the structures of the sugars is thereby provided. This reaction results in the formation from either a 2-desoxyhexose 3-methyl ether or a 3-desoxyhexose 2-methyl ether, of one of the isomers of methoxysuccinic acid, which is usually isolated as the diamide. 

The positive benefits of extracts of two species of Digitalis purpurea (foxglove and lanata) were recognized long before the active constituents were isolated and structurally characterized. The cardiac glycosides, which include digoxin, digitoxin, and deslanoside, exert a powerful and selective positive inotropic action on the cardiac muscle (see Chapter 35). 

FIGURE 35.3 Structural formulas of the aglycones of the cardiac glycosides. 

In contrast to enzyme activities, the definition of the proteo-hormone measurands as well as of many tumor markers and cardiac markers is very critical and several aspects have to be regarded as it concerns the epitope to be detected, the sub-unit to be measured (/3-chain or complete molecule) and finally the glycosidic structure of the molecule. 

This "doubly glycosidic anellation of - formally - a 2,3-diketosugar onto a diol is highly reminiscent structurally of the broad spectrum antibiotic spectinomycin (41) and the cardiac glycosides isolable from the latex and leaves of Calotropis procera (42) a bushy plant indigenious in wide parts of Africa and India. In these, a pyranoid 4-deoxy-2,3-dicarbonyl sugar, which has been... 

Indeed, the insight into the intricate stereochemical details of ensuing reactions of the pyranoid enolone ester bromide 3 - the pyranoid enolone ester 14, de facto, is an actinospectoside derivative, 16 a structural element of the spectinomycin as well as uscharidine-type cardiac glycosides (except for the terminal benzoyloxy group) - eventually led to practical synthetic strategies for their acquisition. 

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