Steroid cardiotonic

The Na+/K+-ATPase as the Molecular Target for Cardiotonic Steroids (CIS) and Palytoxin... 

Cardiotonic steroids, 30 (1993) 135 Cardiovascular system, effect of azides, 31 (1994) 121... 

Lederer WJ, Hadley RW, Kirby MS, Eisner DA. Inotropic mechanisms in heart muscle cardiotonic steroids—how do they work In Gwathmey JK, Briggs GM, Allen PD, eds. Heart failure. Basic science and clinical aspects. New York Marcel Dekker, 1993 349-365. 

Certain steroids derived from plants are potent inhibitors (K 10 nM) of the Na+-K+ pump. Digitoxigenin and ouabain are members of this class of inhibitors, which are known as cardiotonic steroids because of their strong effects on the heart (Figure 13.7). These compounds inhibit the dephosphorylation of the E2-P form of the ATPase when applied on the... 

Figure 13.7. Digitoxigenin. Cardiotonic steroids such as digitoxigenin inhibit the Na+-K+ pump by blocking the dephosphorylation of E2-P.

Meerwein-Ponndorf reduction. This method is the reverse of the Oppenauer oxidation. A ketone is reduced to an alcohol by treatment with an alcohol and a base. Engel38 was interested in the reduction of 3-ketosteroids of the 5/3-series to the axial 3/3-alcohol. a system present in the active cardiotonic steroids. After exploring catalytic reductions with limited success, he turned to the Meerwein-Ponndorf method using sec.-butyl alcohol and aluminum f-butoxide in refluxing absolute benzene. One interesting observation is that the reduction is complete in about 15 min furthermore, yields of 60% of the axial alcohol can be obtained if the reaction is stopped at this point. Prolonged reaction leads to an increase in the yield of the thermodynamically more stable equatorial alcohol. 

Figure 10 Cardiotonic steroids isoiated from insects. Caiotropin (27) from Danaus butterflies and three representative firefly lucibufagins (3, 28, 29).

The pyrido[2,3-/ ]pyrazines, 185-187, have been identified in the defensive secretion of the giant springtail, Tetrodontophora hidanensisP The secretion appears to confuse and strongly disorient potential predators. An unusual quinoline-derived betaine (188) with defensive properties was recently identified from the blood of Photuris versicolor fireflies. In addition, these fireflies chemical defense relies on sequestered cardiotonic steroids, the lucibufagins (see Section 2.04.3.3) (Figure 44). ... 

Steroidal ketones have been used extensively in the Knoevenagel reaction. Thus, die transformation of 17-oxoandrostane derivatives (309), which are readily available by microbiological degradation of sitosterin, are employed for the synthesis of enantiomerically pure cardiotonic steroids such as bufa-dienolide and cardenolide (311). In toth syntheses the substitutent at C-17 is introduced by a Knoevenagel reaction of the 17-oxoandrostane derivative (309) with ethyl cyanoacetate in the presence of ammonium acetate to give the cyano ester (310), presumably as a mixture of the ( )- and (Z)-isomers, in 89% yield.5 5... 

The structure of digitoxin, one of the cardiotonic steroids produced by the foxglove plant. 

The cardiotonic steroids are extremely strong heart stimulants. A dose as low as 1 mg increases the stroke volume of the... 

Digitalis can be used to control congestive heart failure, but the dose must be carefully determined and monitored because the therapeutic dose is close to the dose that causes toxicity. The symptoms that result from high body levels of cardiotonic steroids include vomiting, blurred vision and lightheadedness, increased water loss, convulsions, and death. Only a physician can determine the inihal dose and maintenance schedule for an individual to control congestive heart failure and yet avoid the toxic side effects. 

---