Synthesis of (S)-5,6-Dibromo-tryptophan derivatives as building blocks for peptide chemistry

5,6-Dibromo-tryptophan and its derivatives are found in a variety of highly bioactive natural compounds. Notwithstanding its relevance, no synthetic pathway was found in the literature. Here, an efficient pathway for the synthesis of 5,6-dibromotryptophan derivatives is reported [1]. Selective bromination [2] at position 5 of 6-Br-isatin was followed by BH₃ reduction of the intermediate α-keto-amide and alkylation with Ser-OH in Ac₂O/AcOH. Optical resolution of the obtained racemic mixture was carried out by enzymatic de-acetylation [3]. Finally, an in situ N ^α-Boc protection of the optically pure S form yielded the desired N ^α-Boc-(S)-5,6-dibromo-tryptophan.