Tryptophan Analogues with Fixed Side-Chain Orientation: Expanding the Scope
Lennart Nicke1, Philip Horx1, Ronny Müller2
1Faculty of Chemistry, Philipps-University Marburg, Hans-Meerwein-Strasse 4, 35032, Marburg, Germany.
Abstract:
A generalized synthetic strategy is proposed here for the synthesis of asymmetric β-indoylated amino acids by 8-aminoquinoline (8AQ)-directed C(sp3)-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-NH2 (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.
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