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

5,6-Dibromo-tryptophan is an interesting amino acid whose derivatives and analogues are found in a variety of highly bioactive natural compounds. Notwithstanding its relevance no data concerning this compound are found in the literature. Here an efficient pathway for the synthesis of 5,6-dibromo-tryptophan derivatives is reported. The reaction is performed by using 6-Br-isatin as starting material. Selective bromination at position 5 was followed by BH3 reduction of the intermediate α-keto-amide and alkylation with Ser-OH in Ac2O/AcOH. Optical resolution was effected by enzymatic de-acetylation of the obtained racemic mixture. Finally, in situ Nα-Boc protection of the optically pure S form yielded the desired Nα-Boc-(S)-5,6-dibromo-tryptophan.