Formal synthesis of vallesamidine

Abstract

A novel route to the racemic selenide (1RS, 12bRS)-1-ethyl -2,3,6,7,12,12b-hexahydro-1- [2(phenylseleno)ethyl]indolo[2,3-a]quinolizin-4(1H)-one (13b), a key intermediate in the total synthesis of vallesamidine (1), was elaborated. Compound 3a, obtained by Pictet-Spengler reaction of tryptamine and cyclohept-4-enyl-1-carbaldehyde (2c), was oxidized with KMnO4 to the diacid 4, which was subsequently converted into the isomeric tetracyclic lactams 5a,b. After proper protection maneuvers, Barton decarboxylation of 10a,b, trapping with PhSe2Ph, and Boc removal afforded 13b.