Steroids cardenolides 359

The most difflcult pharmaceutically relevant oxidation of steroids is the introduction of a 14 -hydroxyl group. This functional group is found in heart-active steroids (cardenolides) such as digitoxigenin, which also contain a 17/J-butenolide substituent. The 14/ -hydroxyl group is easily cleaved off by dehydration and must therefore not be treated with Lewis or... 

Cardiac glycosides are medicinally important steroids. Cardenolides are used in heart therapy, as emetics, diuretics, and purgatives. They affect the Na+/K+-ATPase and are very toxic at high doses. 

Various aspects of steroid biosynthesis were included in a Royal Society Symposium. The published proceedings and other reviews have dealt with cyclase enzymes,water-soluble steroids and triterpenoids, the involvement of a 14(15)- or 8(14)-double bond and its reductionin cholesterol biosynthesis, biosynthesis of sterols, steroid metabolism in insects, pregnane steroids, cardenolides, and bufadienolides. ... 

When used at room temperature in the presence of an active platinum catalyst in an inert solvent, e.g., acetone or ethyl acetate, oxygen will oxidize nonhindered, saturated hydroxyl groups and exposed allylic alcohols. This reagent has found extensive use in sugar chemistry and is particularly suited for the selective oxidation of either 3a- or 3j -alcohols of steroids. Other hydroxyl groups on the steroid skeleton are much less sensitive to oxidation. As a result, this reaction has been used extensively in research on polyhydroxy cardiac-active principles, e.g., the cardenolides and bufadienolides, where the 3-hydroxyl group is easily oxidized without extensive oxidation or dehydration of other hydroxyl groups. The ordinarily difficult selective oxidation of the... 

Na+/K+-ATPase. Figure 2 Specific Inhibitors of Na+/K+-ATPase. (a) Endogenous cardiac glycosides identified in mammals. Substances with a 5-membered lactone at position C17 of the steroid moiety are referred to as cardenolides, those with a 6-membered lactone as bufadienolides. (b) Palytoxin (C P NsO ) produced by corals of the genus Palythoa. 

The y-lactone ring of the steroid skeleton forms an intermediate cardenolide anion in alkaline medium that nucleophilically adds to the 3,5-dinitrobenzoic acid in the position ortho to the two nitro groups. A mesomerically stabilized red-violet anion is produced (Meisenheimer complex). 

FIGURE 11.7 Cardiac glycosides consist of a sugar, a steroid skeleton, and a lactone ring. A five-membered lactone ring as here occurs in the cardenolide type. 

Defensive/ants, birds, monk isopr. (cardenolide steroids C 8.1.1) danaid butterflies larvae. Ins., as plant dietary metabolites... 

Cardenolldes appear to be metabolized by a variety of species, possibly as a mechanism for converting these steroids into compounds that can be efficiently sequestered. The milkweed bug, Oncopeltus fasclatus, metabolizes (hydroxylates ) the nonpolar cardenollde dlgltoxln to more polar compounds that are subsequently sequestered In the dorsolateral space fluid (17. 18). Larvae of another cardenolide-adapted Insect, the monarch butterfly, Danaus plexlppus. also convert these steroids Into compounds that are readily sequestered. For example, uscharldln, which contains a carbonyl group at C-3 ( ) of the... 

The cardenolides in the larval hemolymph are about at an equivalent concentration with those distributed in the other larval tissues, negligible amounts of these steroids being present in the gut (26). In the adult, cardenolides are equally distributed between the three main body regions and the wings, with females containing about twice as much of these steroids as males. This female bias in cardenolide concentration appears to be directly attributable to the presence of substantial amounts of these steroids in the eggs. 

Larvae of Inoplnatus emerge as major sequestrators of cardenolides primarily because their hemolymph, which is present in a relatively large volume, effectively sequesters high concentrations of polar cardenolides (26). Cardenolide excretion largely reflects loss of these steroids as components of the larval exuviae, the concentration of these compounds becoming relatively stable after pupal ecdysis. These steroids are ubiquitously distributed in the adult moth, having been derived primarily from the rich cardenolide pool in the larval blood. 

Comparison with the complete 13C NMR signal assignments of steroids enabled the interpretation of the 13C NMR spectra of structurally related cardenolides and sapogenins [596, 597]. Besides single-frequency off-resonance decoupling and low power noise decoupling, spectra of specifically deuterated compounds were used as additional aids for the signal identifications. The 13C chemical shifts are collected in Table 5.12 and the... 

Butenolides. 21-Hydroxy-20-keto steroids react with 1 to form cardenolides by an intramolecular Wittig reaction (equation I).2... 

All of the cardiac glycosides, or cardenolides—of which digoxin is the prototype—combine a steroid nucleus linked to a lactone ring at the 17 position and a series of sugars at carbon 3 of the... 

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