Spiroligustolides A and B: Two pairs of enantiomeric spiro-orthoester-containing phthalide dimers as Cav3.1 calcium channel inhibitors from Ligusticum Chuanxiong Hort

Two pairs of unprecedented enantiomeric phthalide dimers, spiroligustolides A (1a/1b) and B (2a/2b), featuring a unique spiroorthoster linkage between two monomeric units to form a 5/6/5/6/6-fused ring system, were isolated from the roots of Ligusticum chuanxiong. The structures and relative configurations of 1 and 2 were determined by HR-ESI-MS, IR, and NMR spectroscopic data, coupled with single-crystal X-ray diffraction analysis, and the absolute configurations of 1a, 1b, 2a, and 2b were established by comparing the experimental and calculated electronic circular dichroism (ECD) data. Plausible biosynthetic pathway for 1 and 2 was proposed. Moreover, compounds 1, 1b, and 2b showed remarkable inhibitory activities on Ca(v)3.1 calcium channel with IC50 values of 8.34, 7.08, and 8.60 mu M, respectively.

Automated summary

Two pairs of unprecedented enantiomeric phthalide dimers, spiroligustolides A and B, were isolated from the roots of Ligusticum chuanxiong. Their structures and relative configurations were determined by various analytical methods, and their absolute configurations were established through electronic circular dichroism (ECD) data. The possible biosynthetic pathway of these compounds was proposed. Furthermore, compounds 1, 1b, and 2b exhibited significant inhibitory activities on Ca(v)3.1 calcium channel.