Epoxymicranthols A—N, 5,9‐Epoxygrayanane Diterpenoids as Potent Analgesics from Rhododendron micranthum

Abstract

Main observation and conclusion Fifteen 5,9‐epoxygrayanane diterpenoids (1—15) including fourteen new ones, epoxymicranthols A—N (1—14), were isolated from the leaves extract of Rhododendron micranthum. Their structures were elucidated via extensive spectroscopic methods and 13C NMR‐DP4+ analysis, and the absolute configurations of 1, 3—10, 14, and 15 were confirmed by single‐crystal X‐ray diffraction analysis. Epoxymicranthols A—C (1—3) represent the first examples of 14α‐hydroxygrayanane diterpenoids, and epoxymicranthols C—F (3—6) are the first examples of 10β‐hydroxy‐5,9‐epoxygrayanane diterpenoids. Meanwhile, epoxymicranthols K (11) and N (14) represent the first examples of 13‐hydroxy‐5,9‐epoxygrayanane and 5,9‐epoxygrayan‐3‐one diterpenoids, respectively. All the diterpenoids (1—15) were assayed for their analgesic activities, and all of them exhibited significant analgesic activities at a dose of 5.0 mg/kg. Among them, compounds 2, 7, 8, and 10 also exhibited significant analgesic activities even at lower doses of 1.0 and 0.2 mg/kg. More importantly, epoxymicranthol G (7) still expressed potent analgesic activity at a lower dose of 0.04 mg/kg. A preliminary structure‐activity relationship for the analgesic effects of 5,9‐epoxygrayanane diterpenoids 1—15 is discussed. These results not only enlarged the structural diversity of 5,9‐epoxygrayanane diterpenoids, but also provided a basis to develop novel potent analgesics.

Highly Oxygenated Dimeric Grayanane Diterpenoids as Analgesics: TRPV1 and TRPA1 Dual Antagonists from Rhododendron molle

“…The procedures of intensity data collection, structure solution, reduction, and hydrogen atoms treatment were performed as previously described. [ 26,35 ] The crystal structures of 1 — 3 and 5 were solved and refined by the Olex2 software with ShelXL and ShelXT programs. All non‐hydrogen atoms were refined anisotropically using the full‐matrix least‐squares method.…”

“…In an effort to search for potent analgesics from Chinese medicinal plants, [ 26,30‐31 ] three novel dimeric grayanane diterpenoids named bismollethers A—C ( 1 — 3 ) (Figure 1), and three known analogues birhodomolleins A—C ( 4 — 6 ), were isolated from the flowers of Rhododendron molle , a natural pain killer, collected at Qichun, Hubei Province, China, which is the hometown of Shizhen Li, a renowned Chinese medicine scientist in Ming Dynasty. Bismollether A ( 1 ) is a caged grayanane diterpenoid dimer linked by two oxygen‐bridges of C‐2 − O − C‐14′ and C‐14 − O − C‐2′, forming a rare symmetric 1,8‐dioxacyclotetradecane motif (Figure 1).…”

“…[ 25 ] Dimeric grayanane diterpenoids are very rare, although over 300 grayanane diterpenoids have been reported. [ 25‐26 ] To date, only seven dimeric grayanane diterpenoids, birhodomolleins A—E, [ 9,27 ] bimollfoliagein A, [ 28 ] and rhodomollein XLIII, [ 29 ] were isolated. However, neither their relative configurations nor their absolute configurations were assigned by more solid evidences such as quantum chemical calculations and single‐crystal X‐ray diffraction.…”

Discovery of Kalmane Diterpenoids as Potent Analgesics from the Flowers of Rhododendron dauricum

“…According to the procedures previously described in the literature, [ 38,41‐43 ] all isolated kalmane diterpenoids ( 1 — 8 ) were evaluated for their analgesic activities using an HOAc−induced writhing test in Kunming mice (20—30 g each) purchased from the Laboratory Animal Center, Tongji Medical College, Huazhong University of Science and Technology. The license number for the use of experimental animals is No.…”

α-Glucosidase Inhibitory Activities and the Interaction Mechanism of Novel Spiro-Flavoalkaloids from YingDe Green Tea

“…The energy of the optimized structures at the B3LYP/6-31 + G­(d) level in the Gaussian 09 software was applied to screen stable conformers. The NMR calculations of all the selected conformers were optimized with the B3LYP/6-31G­(d) mode in the gas phase and calculated using the gauge independent atomic orbital (GIAO) method at the mPW1PW91/6-311G­(d,p) level in DMSO with the Gaussian 09 software. , The calculated NMR data were analyzed by using the DP4+ probability to further confirm the relative configuration of C-5‴ in 1 .…”