Biomimetic Total Synthesis of Ervitsine and Indole Alkaloids of the Ervatamine Group via 1,4-Dihydropyridines

Citations Over TimeTop 10% of 1997 papers

Abstract

Addition of the enolate derived from 2-acetylindole 1a to pyridinium salt 2 followed by in situ trapping of the initially formed 1,4-dihydropyridine 3a with Eschenmoser's salt gives tetracycle 5a. Subsequent elaboration of the exocyclic methylene and E-ethylidene substituents leads to Na-methylervitsine (17a). A similar sequence from the Na-protected 2-acetylindole 1c establishes the first total synthesis of the 2-acylindole alkaloid ervitsine. Alternatively, dihydropyridine 3a is trapped with BrSePh to give the tetracyclic selenide 7a, which is then converted to Na-methylervitsine by way of selenoxide 20. The synthesis of the alkaloids of the ervatamine group starts with the addition of the enolate derived from 2-acetyl-1-benzylindole (1g) to pyridinium salt 24 and the conversion of the resulting 1,4-dihydropyridine to 3,5-diacylated dihydropyridine 26g. Chemoselective reduction of the vinylogous amide moiety of 26g, followed by deprotection of the indole ring and LiEt3BH reduction leads to diol 37b. On sequential treatment with Eschenmoser's salt, methyl iodide, NaCNBH3, and MnO2, 37b is converted to the tetracyclic 2-acylindole 39, from which the first total synthesis of 19,20-didehydroervatamine and 20-epiervatamine is accomplished by manipulation of the 1-hydroxyethyl chain. The above syntheses can be considered as biomimetic, as cyclization of the key intermediates I and II mimics the key steps of the biosynthesis of the title alkaloids.

Related Papers

• Strategies and Tactics in Organic Synthesis(1993)
• → Delivery of a Quaternary Pyridinium Salt Across the Blood-Brain Barrier by Its Dihydropyridine Derivative(1975)73 cited
• → Progress toward a biomimetic synthesis of pegaharmaline A(2022)2 cited
• → An approach for measuring in vivo cerebral redox states using the oxidative conversion of dihydropyridine to pyridinium ion and the metabolic trapping principle(2005)7 cited