Neomacrophorin X, a [4.4.3]Propellane-Type Meroterpenoid from Trichoderma sp. 1212-03

Neomacrophorin X (1) was isolated from Trichoderma sp. 1212-03. Heteronuclear multiple bond correlation (HMBC) spectral analysis indicated a unique [4.4.3]propellane framework, which was verified by the ¹H and ¹³C chemical shift calculations based on density functional theory (DFT) and subsequent comparison with experimental data obtained in CDCl₃. The DFT-based electronic circular dichroism (ECD) calculations were effective in not only determining the absolute configuration but also confirming the relative structure. The predominant conformation of 1 was found to be solvent-dependent, with different conformations presenting different NMR and ECD profiles. Introduction of J-based analysis with a J-resolved HMBC aided in this investigation. This conformational alternation was reproduced by considering the solvation with the SM5.4 model in the calculation, although it was not sufficiently quantitative. Although the calculations without solvent effects suggested a conformer that satisfies the spectral profiles in CDCl₃, postcalculations with the SM5.4 solvation protocol stabilized the second major conformer, which reproduces the NMR and ECD profiles in polar solvents. Neomacrophorin X (1) is assumed to be biosynthesized by a coupling between the reduced form of anthraquinone and a neomacrophorin derivative. This hypothesis was supported experimentally by the isolation of pachybasin and chrysophanol, as well as acyclic premacrophorin (2), from the same fungus. Some biological properties of 1 are described.