Prolinimines: N‑Amino‑l‑Pro-methyl Ester (Hydrazine) Schiff Bases from a Fish Gastrointestinal Tract-Derived Fungus, Trichoderma sp. CMB-F563

A rice cultivation of a fish gastrointestinal tract-derived fungus, Trichoderma sp. CMB-F563, yielded natural products incorporating a rare hydrazine moiety, embedded within a Schiff base. Structures inclusive of absolute configurations were assigned to prolinimines A–D (1–4) on the basis of detailed spectroscopic and C₃ Marfey’s analysis, as well as biosynthetic considerations, biomimetic total synthesis, and chemical transformations. Of note, monomeric 1 proved to be acid labile and, during isolation, underwent quantitative transformation to dimeric 3 and trimeric 4. Prolinimines are only the second reported natural products incorporating an N-amino-Pro residue, the first to include l-Pro, the first to occur as Schiff bases, and the first to be isolated from a microorganism.