Catalytic asymmetric synthesis of protected tryptophan regioisomers

Article abstract of DOI:10.1021/jo025964i

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.