Catalytic Asymmetric Synthesis of Protected Tryptophan Regioisomers

Abstract

Tryptophan 1 (Trp) is superior to all other naturally occurring peptide residues in its ability to bind cations (the cation−π interaction). In an effort to expand the toolbox of Trp-like amino acids, in this note we report catalytic asymmetric syntheses of Trp regioisomers 2a−e, where the alanine unit is attached not to C-3 of indole but to C-2, C-4, C-5, C-6, or C-7. Excellent asymmetric induction is obtained in each case (generally >97% ee). Ab initio calculations suggest that the indole nuclei of 2a−e will bind Na+ with the same affinity as that of Trp