Tryptophan Analogues with Fixed Side‐Chain Orientation: Expanding the Scope

A generalized synthetic strategy is proposed here for the synthesis of asymmetric β‐indoylated amino acids by 8‐aminoquinoline (8AQ)‐directed C(sp(3))‐H functionalization of suitably protected precursors. Peptides containing one of the four stereoisomers of (indol‐3‐yl)‐3‐phenylalanine at position 2 of the parent peptide KwFwLL‐NH(2) (w=d‐Trp) cover a wide range of activities as ghrelin receptor inverse agonists, among them the most active described until now. This application exemplarily shows how β‐indoylated amino acids can be used for the systematic variation of the position of an indole group in a bioactive peptide.