Further Thymol Derivatives from Ageratina cylindrica

Abstract

From the leaves of Ageratina cylindrica, in addition to the described [(2S)-2-{4-formyl-5-hydroxy-2-[(2-methylpropanoyl)oxy]phenyl}oxiran-2-yl]methyl benzoate (cylindrinol A, 8), seven new thymol derivatives were isolated and named cylindrinols B - H (1 - 7). The structures of these compounds were established as (2-{4-(hydroxymethyl)-2-[(2-methylpropanoyl)oxy]phenyl}oxiran-2-yl)methyl benzoate (1), (2-{4-formyl-2-[(2-methylpropanoyl)oxy]phenyl}oxiran-2-yl)methyl benzoate (2), (2-{4-[(acetyloxy)methyl]-2-[(2-methylpropanoyl)oxy]phenyl}oxiran-2-yl)methyl benzoate (3), [2-(2-[(2-methylpropanoyl)oxy]-4-{[(2-methylpropanoyl)oxy]methyl}phenyl)oxiran-2-yl]methyl benzoate (4), [2-(5-hydroxy-2-[(2-methylpropanoyl)oxy]-4-{[(2-methylpropanoyl)oxy]methyl}phenyl)oxiran-2-yl]methyl benzoate (5), 2-{4-(hydroxymethyl)-2-[(2-methylpropanoyl)oxy]phenyl}prop-2-en-1-yl benzoate (6), and 2-hydroxy-2-[2-hydroxy-4-(hydroxymethyl)-phenyl]-3-[(2-methylpropanoyl)oxy]propyl benzoate (7), by spectroscopic means. Compounds 1 showed moderate antiprotozoal activity on both protozoa. Compounds 4 and 5 showed selectivity on Giardia lamblia trophozoites. All isolated compounds were less active than two antiprotozoal drugs, metronidazole and emetine, used as positive controls. Compound 5 exhibited a high inhibitory effect on hyperpropulsive movement of the small intestine in rats; its effect was best than loperamide, antidiarrheal drug used as a positive control.

Methodology for the Absolute Configuration Determination of Epoxythymols Using the Constituents of Ageratina glabrata

“…A minor byproduct was detected during the progress of these experiments, which was isolated and identified as 10benzoyloxy-9-isobutyryloxy-6,8-dihydroxythymol (Figure S25, Supporting Information). This ring-opening product may be formed by attack of a H 2 O molecule to C-8 with the concerted epoxide ring rupture at the C-8−O-8 bond followed by transesterification of the isobutyryl residue from O-3 to O-9, as suggested by Bohlmann et al 5 On the basis of the NMR data of this substance and the pertinent observations made by Bustos-Brito et al, 28 we are herein proposing the revision of the 10benzoyloxy-6,8,9-trihydroxythymol isobutyrate structure reported by our research group 29 to 10-benzoyloxy-9-isobutyryloxy-6,8-dihydroxythymol, since the spectroscopic data are identical to those provided in this paper (Figures S26 and S28, Supporting Information).…”

“…At the same time, such an experiment could provide useful data to understand the susceptibility in the racemization of epoxythymols. Transesterification with oxirane cleavage of some epoxythymol derivatives has been proposed, , but the oxirane racemization has not been documented. Thus, epoxythymol 1 was selected to explore its racemization because it was isolated in good yields.…”

Essential Oils and Terpenic Compounds as Potential Hits for Drugs against Amitochondriate Protists

“…In another study, a clerodane diterpene, linearolactone (LL), isolated from Salvia gesneriflora , presented an IC 50 of 28.2 μM against G. duodenalis trophozoites [ 72 ]. A significant giardicidal effect was also seen to be exerted by ent-Kaurene glycosides (41.9–48.9 μM) [ 73 ], thymol derivatives (IC 50 = 151.1–167.4 μM) [ 18 , 74 ], trinervinol (IC 50 = 2.03 μg/mL), and piquerol (IC 50 = 2.42 μg/mL) [ 75 ]. Other promising anti- G. duodenalis essential oil derivatives are eugenol, linalool [ 55 ], dihydroartemisinin [ 76 ], 7-hydroxy-3,4-dihydrocadalene, 7-hydroxycalamenene [ 77 ], incomptine A [ 78 ], anethole, carvacrol, cinnamaldehyde, cuminaldehyde, eucalyptol, limonene, and thymol [ 58 ].…”

“…The EOs and their related compounds have great commercial value and are widely used in traditional medicine, by phytotherapy practitioners, and in public health services for the treatment of several conditions, including dermatological problems, microbial resistance, and parasitic diseases [ 17 ]. Several plant EOs and terpenic compounds (e.g., diterpenes, triterpenes, and other terpenoids) have demonstrated antiparasitic effects [ 18 , 19 , 20 , 21 , 22 ].…”