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

Liu-Yan Wang; Wen-Yan Li; Hao-Feng Zhou; Xue-Yu Zhao; Xiao-Nian Li; Xing-De Wu; Qin-Shi Zhao

doi:10.1016/j.bioorg.2022.105749

Spiroligustolides A and B: Two pairs of enantiomeric spiro-orthoester-containing phthalide dimers as Ca_v3.1 calcium channel inhibitors from Ligusticum Chuanxiong Hort

Bioorg Chem. 2022 Jun:123:105749. doi: 10.1016/j.bioorg.2022.105749. Epub 2022 Mar 26.

Authors

Liu-Yan Wang¹, Wen-Yan Li², Hao-Feng Zhou², Xue-Yu Zhao¹, Xiao-Nian Li², Xing-De Wu³, Qin-Shi Zhao⁴

Affiliations

¹ State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, PR China; School of Pharmaceutical Science and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming 650500, PR China.
² State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, PR China.
³ State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, PR China; Key Laboratory of Ethnic Medicine Resource Chemistry, State Ethnic Affairs Commission & Ministry of Education, Yunnan Minzu University, Kunming 650500, PR China. Electronic address: wuxingde@mail.kib.ac.cn.
⁴ State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, PR China. Electronic address: qinshizhao@mail.kib.ac.cn.

PMID: 35364556
DOI: 10.1016/j.bioorg.2022.105749

Abstract

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_v3.1 calcium channel with IC₅₀ values of 8.34, 7.08, and 8.60 μM, respectively.

Keywords: Ca(v)3.1 calcium inhibitor; Ligusticum chuanxiong Hort; Phthalide dimer; Spiroorthoester.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Benzofurans* / chemistry
Benzofurans* / pharmacology
Calcium Channels
Ligusticum* / chemistry
Molecular Structure
Stereoisomerism

Substances

Benzofurans
Calcium Channels
phthalide