A pair of new enantiomeric hybrid phthalide–adenines with a rare 5-oxa-1-azaspiro[3,4]octane moiety and two pairs of new enantiomeric hybrid paraethyl phenol–adenines from Ligusticum chuanxiong

Abstract

Three pairs of new enantiomeric adenine alkaloids, (+)/(−)-liguadenines A–C [(+)/(−)-1–3], were isolated from the rhizome of Ligusticum chuanxiong Hort. The structures and absolute configurations of these compounds were determined using spectroscopic data, single-crystal X-ray diffraction, and electronic circular dichroism analyses. To the best of our knowledge, compounds (+)-1 and (−)-1 are the first hybrid phthalide–adenines to be ever reported. The linkage between the phthalide and adenine units in these compounds forms a rare 5-oxa-1-azaspiro[3,4]octane moiety. Analyses of the anti-inflammatory activities of the isolated compounds show that (+)/(−)-1 and (+)-3 exhibit significant inhibitory activity against LPS-induced TNF-α and IL-6 production in RAW264.7 cells. RT-qPCR analysis confirms that the most active compound, (+)-3, exerts anti-inflammatory activity by downregulating the mRNA expressions of TNF-α and IL-6 in the cells.

Keywords

• Ligusticum chuanxiong
• Enantiomers
• Adenine alkaloids
• Hybrid phthalide–adenines
• Hybrid paraethyl phenol–adenines
• Anti-inflammatory activity