Synthesis of spirolactones by 1,3-dipolar cycloadditions to methyl (S)-3-[(E)-cyanomethylidene]-2-oxotetrahydrofuran-5-carboxylate (original) (raw)
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Synthesis of Some Novel ?-Spirolactones
Monatshefte f�r Chemie / Chemical Monthly, 2004
We report on the addition of dialkyl acetylenedicarboxylate to 1-alkylisatins or tryptanthrine in the presence of triphenylphosphine which leads to highly functionalised novel unsaturated -spirolactones.
Facile Preparation of Spirolactones by an Alkoxycarbonyl Radical Cyclization Cross-Coupling Cascade
Angewandte Chemie International Edition
An alkoxycarbonyl radical cyclization crosscoupling cascade has been developed that allows functionalized -butyrolactones to be prepared in one step from simple tertiary alcohol-derived homoallylic oxalate precursors. The reaction succeeds with aryl and vinyl electrophiles and is compatible with heterocyclic fragments in both coupling partners. This chemistry allows for the rapid construction of spirolactones, which are of interest in drug discovery endeavors.
Spironolactone is a well-known multi-target drug and is specifically used for the treatment of high blood pressure and heart failure. It is also used for the treatment of edema, cirrhosis of the liver, malignant, pediatric, nephrosis and primary hyperaldosteronism. Spironolactone in association with thiazide diuretics treats hypertension and in association with furosemide treats bronchopulmonary dyspepsia. The therapeutic mechanism of action of spironolactone involves binding to intracellular mineralocorticoids receptors (MRs) in kidney epithelial cells, thereby inhibiting the binding of aldosterone. Since its first synthesis in 1957 there are several synthetic approaches have been reported throughout the years, Synthetic community has devoted efforts to improve the synthesis of spironolactone and to synthesize its analogues and derivatives. This review aims to provide comprehensive insight for the synthetic endeavors devoted towards the synthesis of a versatile drug spironolactone and its analogues/derivatives.