Menthane-type monoterpenes from Achillea biebersteinii Afan.: stereochemical elucidation and anti-inflammatory...

Thirty-three menthane-type monoterpenes, including fifteen pairs of enantiomers, were isolated and identified from the aerial parts of Achillea biebersteinii Afan. collected in Tashkent, Uzbekistan. These compounds comprised seventeen undescribed compounds named (±)-biebersteinins A-H and biebersteinins I, eleven previously unreported natural products, and five known analogues. Their structures were comprehensively elucidated by extensive spectroscopic analyses, including HRESIMS and NMR, single-crystal X-ray diffraction, ¹³C NMR calculations combined with DP4+ probability analysis, ECD calculations, and comparison to literature. The stereochemical assignment of a previously reported monoterpene was revised on the basis of X-ray crystallographic evidence, highlighting the limited diagnostic value of certain NOESY correlations in 4-isopropyl-substituted menthane-type monoterpenes. In addition, the absolute configurations of nine previously unreported natural products and two known compounds were determined by experimental and calculated ECD data for the first time. Fourteen compounds exhibited weak to moderate inhibitory effects on NO production in LPS-stimulated BV2 cells.