New asymmetric route to bridged indole alkaloids: formal enantiospecific syntheses of (-)-suaveoline, (-)-raumacline and (-)-Nb-methylraumacline

Abstract

The homologous nitrile 13 derived from L-tryptophan undergoes a modified Pictet–Spengler reaction with methyl propynoate, under conditions of kinetic control, to afford the cis-tetrahydro-β-carboline 15a (cis∶trans = 77∶23). After protection, Dieckmann–Thorpe cyclisation to the bridged keto nitrile 20 proceeds in 90% yield. Simple functional group modifications via the alcohol 21a and nitrile 22 (structures confirmed by X-ray crystallography) allow convergence with the tetracyclic α,β-unsaturated aldehyde 10, which is an advanced intermediate for the synthesis of a range of bridged indole alkaloids.