Synthesis of tryptophan from gramine

Gramine, obtained from indole by the Mannich reaction, is heated with diethyl acetamidomalonate and a catalytic amount of base. Dimethylamine is eliminated to form a 3-methyleneindolenine, a Michael acceptor, to which the malonate enolate adds.

Hydrolysis of the esters and decarboxylation of the resulting malonic acid, followed by hydrolysis of the acetamide, give racemic tryptophan. It is the indole version of the acetamidomalonate amino-acid synthesis; the L enantiomer is then separated by enzymatic resolution.