Dolichocarpols A-F, Unprecedented Macrocyclic Humulene-Type Sesquiterpenoids from Anaxagorea dolichocarpa

Abstract

Six sesquiterpenoids with unprecedented macrocyclic humulene-type structures, namely, dolichocarpols A-E (1− 5) with ether-bridged bicyclic rings between C-10 and C-2, C-10 and C-7, C-10 and C-6 (×2), and C-6 and C-3 and dolichocarpol F (6) cyclized between C-7 and C-2 and with an ether bridge between C-10 and C-3, were isolated from Anaxagorea dolichocarpa roots. The structures of the compounds were elucidated by NMR, MS, and IR data. Absolute configurations of compounds 1−3 and 6 were established on the basis of data from electronic circular dichroism, whereas relative configurations of compounds 4 and 5 were suggested by the NOESY spectrum. In addition, a putative biosynthetic pathway of the compounds is proposed. Furthermore, the cytotoxicity of 3, 4, and 6 against HCT-116 (human colorectal carcinoma) and L929 (murine fibroblast) was evaluated.

Structure Revision of the Sesquiterpene Nordine Based on NMR Spectroscopic Analysis and X-ray Crystallography

“…Thus, the molecular structure was confirmed, and the result showed a five-membered ring cyclized between C-10 and C-7 and hydroxyl groups at C-6 and C-2. In addition, the NMR data obtained from other sesquiterpenoids isolated from A. dolichocarpa and Xanthium spinosum corroborated our proposal.…”

“…The 1D and 2D NMR data for 1 (Table ) were identical to those described for nordine . However, according to the literature, − the chemical shifts at δ C 87.8, 84.4, and 73.7, which were attributed to C-10, C-7, and C-6 are consistent with the ether fusion between C-10 and C-7 and not C-10 and C-6, as determined by Husain et al In the HMBC spectrum, the signal at δ H 4.42 (H-2) showed a correlation with the carbons at δ C 46.1, 157.0, 35.8, and 112.6, which were assigned to C-1, C-3, C-11, and C-12, respectively. The signals at δ H 5.29 and 5.00 (H 2 -12) correlated with the carbons at δ C 69.4 and 32.4, which were assigned to C-2 and C-4, respectively, confirming the insertion of a hydroxy group at C-2.…”

“…In our continuing study of humulene-type sesquiterpenes from Anaxagorea dolichocarpa Sprague & Sandwith, 10 we isolated nordine and realized that the values of chemical shifts for the carbons C-6 and C-7 may indicate another ether fusion. Thus, we suggest that the structure of nordine involves an ether cycle between carbons C-10 and C-7, which is also compatible with other reported compounds.…”

“…In our continuing study of humulene-type sesquiterpenes from Anaxagorea dolichocarpa Sprague & Sandwith, we isolated nordine and realized that the values of chemical shifts for the carbons C-6 and C-7 may indicate another ether fusion. Thus, we suggest that the structure of nordine involves an ether cycle between carbons C-10 and C-7, which is also compatible with other reported compounds. − Therefore, with NMR data analysis and support by literature data, we propose the structure revision of nordine (Figure ) by obtaining the diacetylated derivative and by X-ray crystallography.…”