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

Abstract 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.