Cardiotonic Steroid Glycoside Synthesis

Cardiotonic Steroid Glycoside Synthesis

Author: ChemViews

The active components from the extracts of Digitalis – cardiotonic steroid glycosides – have been referred to as the most ingested drugs in medicine, e.g., for heart failure and abnormal heart rhythms. Their positive inotropic activity has been attributed largely to a high affinity inhibitory interaction with the extracellular surface of the membrane-bound sodium pump Na+/K+-ATPase.

Although several imaginative total synthesis protocols have been described, Brian Heasley, Scynexis, Inc., NC, USA, describes in his review that it is unlikely that meaningful quantities of cardiotonic steroid glycosides like cardenolides and bufadienolides will be produced in this manner. From a pharmaceutical research and development perspective, some of the most practical solutions to the problem of cardiotonic steroid synthesis came from the laboratory of Karel Wiesner in Canada in the 1970s and 1980s. Since then, the arsenal of the modern synthetic chemist has expanded to include a variety of catalytic techniques, olefin functionalization, and transition-metal-mediated technologies.

Given the pharmacologically privileged nature of the steroid scaffold and the vast possibilities for structural diversity when one considers varying stereo-chemical configurations, hydroxylation patterns, and oxidative skeletal rearrangements, Heasley says it is very likely that future work in this recently neglected field will produce biologically interesting medicinal lead compounds that might be further developed into clinically relevant new chemical entities (NCEs).

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