BIOMIMETIC TOTAL SYNTHESIS OF ERVITSINE AND INDOLE ALKALOIDS OF THE ERVATAMINE GROUP VIA 1,4-DIHYDROPYRIDINES

Addition of the enolate derived from 2-acetylindole In to pyridinium s alt 2 followed by in situ trapping of the initially formed 1,4-dihydro pyridine 3a with Eschenmoser's salt gives tetracycle 5a. Subsequent el aboration of the exocyclic methylene and E-ethylidene substituents lea ds to N-a-methylervitsine (17a). A similar sequence from the N-a-prote cted 2-acetylindole Ic establishes the first total synthesis of the 2- acylindole alkaloid ervitsine. Alternatively, dihydropyridine 3a is tr apped with BrSePh to give the tetracyclic selenide 7a, which is then c onverted to N-a-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 (Ig) to pyridinium sa lt 24 and the conversion of the resulting 1,4-dihydropyridine to 3,5-d iacylated dihydropyridine 26g. Chemoselective reduction of the vinylog ous amide moiety of 26g, followed by deprotection of the indole ring a nd LiEt3BH reduction leads to diol 37b. On sequential treatment with E schenmoser's salt, methyl iodide, NaCNBH3, and MnO2, 37b is converted to the tetracyclic 2-acylindole 39, from which the first total synthes is of 19,20-didehydroervatamine and 20-epiervatamine is accomplished b y manipulation of the l-hydroxyethyl chain. The above syntheses can be considered as biomimetic, as cyclization of the key intermediates I a nd II mimics the key steps of the biosynthesis of the title alkaloids.