Protecting-group-free synthesis of the bisindolylmaleimide GF109203X

The bisindolylmaleimide GF109203X is a highly selective inhibitor to Protein Kinase C (PKC) and has attracted much attention. However, its reported synthesis required protecting groups. In order to achieve a short and N-protecting-group-free synthesis of GF109203X, an investigation on N-alkylation of arcyriarubin A was carried out using different bases, solvents and equivalents of bromododecane. It is found that mono-N-alkylation and mono-N′-alkylation could be achieved respectively. Thus, a protecting-group-free synthesis of GF109203X was accomplished in 40% overall yield starting from indole. This work will lead to a short synthesis of mono-N′-alkylated arcyriarubins to accelerate drug discovery.