Discovery of Unusual Ajmaline‐Macroline Type Bisindole Alkaloids from Alstonia macrophylla by Building Blocks‐Based Molecular Networking

Three unusual ajmaline‐macroline type bisindole alkaloids, alsmaphylines A−C, together with their postulated biogenetic precursors, were isolated from the stem barks and leaves of Alstonia macrophylla via the building blocks‐based molecular network (BBMN) strategy. Alsmaphyline A represents a rare ajmaline‐macroline type bisindole alkaloid with an S‐shape polycyclic ring system. Alsmaphylines B and C are two novel ajmaline‐macroline type bisindole alkaloids with N‐1−C‐21' linkages, and the former possesses an unconventional stacked conformation due to the presence of intramolecular noncovalent interactions. The chemical structures including absolute configurations of alsmaphylines A−C were established by comprehensive spectroscopic analyses, electronic circular dichroism (ECD) calculations, and single‐crystal X‐ray crystallography. In addition, a plausible biosynthetic pathway of these bisindole alkaloids as well as their ability to promote the protein synthesis on HT22 cells were discussed.