Bisaspochalasin F: a tetrahydrofuran ring-fused cytochalasan homodimer from an endophytic Aspergillus flavipes as a Cav3.2 inhibitor.

Bisaspochalasin F (1), a new cytochalasan homodimer featuring a fused tetrahydrofuran ring, was isolated from the endophytic fungus Aspergillus flavipes KIB-636, derived from Asarum heterotropoides Fr. Schmidt. Its structure, including the absolute configuration, was unambiguously established by single-crystal X-ray diffraction analysis and comprehensive spectroscopic data. A biomimetic semisynthesis of 1 was successfully achieved from the natural precursor aspochalasin D via LiOH-mediated dimerization. Notably, this dimerization significantly potentiated the inhibitory effect on Cav3.2 calcium channels: compound 1 exhibited an IC50 value of 6.99 ± 0.23 μM, whereas the monomer aspochalasin D was inactive. Consistent with this in vitro finding, 1 demonstrated analgesic efficacy in a mouse acetic acid-induced writhing model at a dosage of 10 mg kg-1, significantly reducing the total number of writhes and prolonging the latency to the first writhe in mice.