Benzyl sulfide, sulfoxide and sulfinate metabolites from Gastrodia elata and their synthesis, derivatization and anti-inflammatory activity

Abstract

Five novel sulfur-containing benzyl metabolites, designated as gastrabenzylsulfoxides A and B (1 and 2), gastrabenzylsulfinate A (3) and gastrabenzylsulfides A and B (4 and 5), along with four known compounds (6−9), were isolated from the aqueous extracts of Gastrodia elata. Compounds 1 and 4 are 4-hydroxy-3-(4′-hydroxybenzyl)benzyl-substituted sulfoxide and sulfide, respectively, which are unprecedented in natural products. Compound 3 represents a rare sulfinate. Several isolates and their sulfone and disulfide analogs (10−13) were synthesized to evaluate their anti-inflammatory activity. Notably, the synthesized sulfone 10 demonstrated significant alleviation of symptoms in multiple in vivo inflammatory models.

Keywords

Gastrodia elata / Sulfur-bearing benzyl metabolites / Synthesis / Anti-inflammatory activity

Funding

This work was supported by the National Natural Science Foundation of China (No. 82293680), the National Science and CAMS Innovation Fund for Medical Science (No. 2021-I2M-1-028), and the Nonprofit Central Research Institute Fund of Chinese Academy of Medical Sciences (No. 2021-RC350-009).

Supporting information

Method for ECD calculation of the stereoisomers of 1−3, bioassay protocols, 1D and 2D NMR spectra, HR-ESI-MS, IR, UV, and ECD data for new compounds 1−5, 1D NMR spectra for the synthetic compounds 2, 3, and 7−13, are available in the Supporting information, and can be requested by sending E-mail to the corresponding author.

Declaration of competing interest

These authors have no conflict of interest to declare.

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