New Oxygenated Methoxy-p-Cymene Derivatives from Leopard's Bane (Doronicum columnae Ten., Asteraceae) Essential Oil: Synthesis Facilitating the Identification of Isomeric Minor Constituents in Complex Matrices.

Species of the genus Doronicum are known for their pharmacological properties and essential oils, the chemical composition of which remains inadequately studied. In this work, GC-MS analysis, synthesis, and spectral techniques (UV, IR, MS, and NMR) were employed to identify 83 constituents in the essential oil from D. columnae roots, which accounted for 98.1% of the total GC-peak area. The major components were thymyl isobutyrate (32.8%) and thymyl 2-methylbutyrate (22.8%), while the minor constituents were methoxy-p-cymene derivatives. Six new natural products were identified through synthesis, GC co-injection experiments and spectral characterization, including esters (isobutyrate, 2-methylbutyrate, and/or isovalerate) of 2-methoxycuminol, 6-methoxythymol, and 6-hydroxythymyl methyl ether, as well as methyl 3-methoxycuminate. Their identification was made possible by synthesis efforts, as isolating pure compounds was impracticable because of their low abundance and the overall structural similarity within the highly complex mixture that was the essential oil.