Biomimetic Transformation of p‑Menthene Glucosides into p‑Cymenes and Carvotanacetone

• Published in: Journal of natural products (Washington, D.C.) Vol. 82; no. 3; pp. 485 - 491
• Main Authors: Pardo-Novoa, Julio C, Arreaga-González, Héctor M, Galván-Gómez, Sinuhé, Rodríguez-García, Gabriela, del Río, Rosa E, Cerda-García-Rojas, Carlos M, Joseph-Nathan, Pedro, Gómez-Hurtado, Mario A
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society and American Society of Pharmacognosy 22.03.2019; Amer Chemical Soc
• Subjects: Chemistry, Medicinal; Life Sciences & Biomedicine; Pharmacology & Pharmacy; Plant Sciences; Science & Technology; ABSOLUTE-CONFIGURATION; ESSENTIAL OIL; IODINE; VOLATILE COMPOUNDS; DERIVATIVES; AROMATIZATION; CONSTITUENTS
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/acs.jnatprod.8b00855

A biomimetic transformation of p-menthene glucosides into aromatic monoterpenoids that alluded to mechanisms for essential oil metabolism, which lines up with the precepts of molecular economy, is described. Acid treatment of (−)-(3S,4S,6R)-3,6-dihydroxy-1-menthene 3-O-β-d-glucopyranoside (1) and (−)-(3S,4R,5R,6S)-3,5,6-trihydroxy-1-menthene 3-O-β-d-glucopyranoside (2), from Ageratina glabrata, yielded p-cymene (7) and carvacrol (9). The stable oxidized intermediates (+)-(3S,4S,6R)-3,6-dihydroxy-1-menthene (3), (+)-(1S,4S,6R)-1,6-dihydroxy-2-menthene (4), (+)-(1R,4S,6R)-1,6-dihydroxy-2-menthene (5), (+)-(4S,6R)-yabunikkeol (6), (+)-(4S)-carvotanacetone (8), (+)-(1S,4S,5R,6R)-1,5,6-trihydroxy-2-menthene (15), (+)-(1R,4S,5R,6R)-1,5,6-trihydroxy-2-menthene (16), and the new (+)-(4S,5R,6S)-1­(7),2-menthadiene (17) permitted establishment of the reaction mechanisms. The reactivity of the hydroxy groups of 4 and 5, as well as those of 15 and 16, was compared by acetylation reactions and supported by DFT calculations, revealing diminished reactivity in 4 and 15 due to the cis configuration of their hydroxy groups at C-1 and C-6. In addition, p-cymene (7) was detected as one of the major constituents of the essential oil of A. glabrata, which matches well with the biomimetic study.