Grayanane Diterpenoids from the Leaves of Rhododendron auriculatum and Their Analgesic Activities

Abstract

Twenty-four grayanane diterpenoids (1–24) including 12 new ones (1–12) were isolated from Rhododendron auriculatum. The structures of the new grayanane diterpenoids (1–12) were defined via extensive spectroscopic data analysis. The absolute configurations of compounds 2–4, 10–12, 14, and 16 were established by single-crystal X-ray diffraction analysis, and electronic circular dichroism data were used to define the absolute configurations of auriculatols D (8) and E (9). Auriculatol A (1) is the first example of a 5,20-epoxygrayanane diterpenoid bearing a 7-oxabicyclo[4.2.1]­nonane motif and a trans/cis/cis/cis-fused 5/5/7/6/5 pentacyclic ring system. Auriculatol B (2) is the first example of a 3α,5α-dihydroxy-1-βH-grayanane diterpenoid. 19-Hydroxy-3-epi-auriculatol B (6) and auriculatol C (7) represent the first examples of 19-hydroxygrayanane and grayan-5(6)-ene diterpenoids, respectively. Diterpenoids 1–24 showed analgesic activities in the writhing test induced by HOAc, and 2, 6, 10, 13, 19, and 24 at a dose of 5.0 mg/kg exhibited significant analgesic effects (inhibition rates >50%). Grayanane diterpenoids grayanotoxins I (19) and IV (24) at doses of 0.2 and 0.04 mg/kg showed more potent analgesic activities than morphine.

Gelstriamine A, a Triamino Monoterpene Indole Alkaloid with a Caged 6/5/7/6/6/5 Scaffold and Analgesic Alkaloids from Gelsemium elegans Stems

“…Analgesic activities of compounds 1 – 17 were assayed in the acetic-acid-induced writhing tests in mice, and morphine (morph) was used as a positive control . Animal experiments (approval number 2018-S748) were approved by the Laboratory Animal Ethics Committee of Tongji Medical College, Huazhong University of Science and Technology.…”

“…The crystallographic data of 5,6,7,8-tetrahydro-3-indol-2-ylisoquinoline ( 17 ) was collected by a Bruker SMART APEX-II CCD diffractometer equipped with a monochromatic fine-focus Cu Kα (λ = 1.541 78 Å). The structure was solved by the procedures described previously . The crystallographic data for compound 17 has been deposited at the Cambridge Crystallographic Data Centre (deposition numbers CCDC 2046375).…”

“…In a course of search for novel analgesics from traditional Chinese medicines, − and expecting the other plant parts to be chemically distinct from the previously well-studied leaves and roots, the stems of G. elegans were investigated, leading to the isolation of a novel triamino monoterpene indole alkaloid with an unprecedented skeleton, gelstriamine A ( 1 ), four new monoterpene indole alkaloids 2 – 5 , and 12 known analogues 6 – 17 (Chart ).…”

Spirocyclic Motifs in Natural Products

“…This compound is the first example of a 5,20-epoxygrayanane diterpenoid bearing a 7-oxabicyclo[4.2.1]nonane motif and a trans/cis/cis/cis -fused 5/5/7/6/5 pentacyclic ring system. Auriculatol A showed analgesic activity in the acetic acid-induced writhing test [96].…”

Sex-dependent variations in anti-nociceptive and antipyretic effects of rhizome and stem extract of Schumannianthus dichotomus Roxb. in male and female mice

“…Folkloric uses of plants against different diseases act as a pivot to explore those plants for new bioactive compounds and affirmative activities of crude plant extracts usher identification and isolation of many compounds. For instance, in recent years, several compounds from plant sources have been reported to possess antinociceptive (Mizokami et al, 2012;Nieto et al, 2013;Sun et al, 2019) and antipyretic effect (Lee et al, 2019;Muhammad et al, 2019). A good number of plants native to Bangladesh have been traditionally used against pain and fever and their effects are underpinned by experimental findings in animal model (Ferdous et al, 2020;Roy et al, 2019;Subedi et al, 2016).…”