Synthesis of tryptophan-dehydrobutyrine diketopiperazine and biological activity of hangtaimycin and its co-metabolites

Houchao Xu, Anne Wochele, Minghe Luo, Gregor Schnakenburg, Yuhui Sun, Heike Brötz-Oesterhelt, and Jeroen S. Dickschat*

Beilstein Journal of Organic Chemistry 2022, 18:1159-1165

Epub Date: 7 September 2022

DOI: 10.3762/bjoc.18.120


An improved synthesis for tryptophan-dehydrobutyrine diketopiperazine (TDD), a co-metabolite of the hybrid polyketide/non-ribosomal peptide hangtaimycin, starting from ʟ-tryptophan is presented. Comparison to TDD isolated from the hangtaimycin producer Streptomyces spectabilis confirmed its S configuration. The X-ray structure of the racemate shows an interesting dimerisation through hydrogen bridges. The results from bioactivity testings of hangtaimycin, TDD and the hangtaimycin degradation product HTM222 are given.