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

Abstract

Kalmane diterpenoids, featuring a 5/8/5/5 tetracyclic carbon skeleton, are very rare in nature. The flowers of Rhododendron dauricum L. (Ericaceae) were phytochemically investigated for the first time, leading to the isolation of eight kalmane diterpenoids (1-8) including four new ones, named rhodokalmanols A-D (1-4). The structures of 1-8 were elucidated by comprehensive spectroscopic methods and 13 C NMR-DP4+ analysis, and the absolute configurations of 1, 2, 4, and 5 were defined by single-crystal X-ray diffraction analysis with Cu Kα radiation. Rhodokalmanol A (1) represents the first 5,8-epoxykalmane diterpenoid and also the first kalm-15(16)-ene diterpenoid. Rhodokalmanols B-D (2-4) are the first examples of kalm-7(8)-ene, kalm-16( 17)-ene, and 8α-methoxykalmane diterpenoids, respectively. All the isolated kalmane diterpenoids 1-8 exhibited significant analgesic effects, and rhodokalmanol C (3) and kalmanol (8) expressed more potent analgesic activity than morphine at doses of 0.2 and 0.04 mg/kg. The preliminary structure-activity relationships of kalmane diterpenoids as potent analgesics are discussed.

Asymmetric total synthesis of montanine-type amaryllidaceae alkaloids

“…2). [45][46][47][48] The experimental ECD spectrum of our synthetic 5 matched well with the calculated spectrum of (3S,4aS,5R,11R,11aR)-5, while being opposite to that of (3R,4aR,5S,11S,11aS)-5. Thus, the absolute configuration of our synthetic 5 was assigned 3S,4aS,5R,11R,11aR.…”

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

“…According to the procedures described in the literature, [ 30 ] the analgesic evaluation of dimeric grayanane diterpenoids 1 — 6 was carried out using an acetic acid‐induced writhing model in mice. Morphine (morph) and saline (5.0 mL/kg) were used as a positive drug and the vehicle control, respectively.…”

“…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).…”

Novel Flavonol Alkaloids in Green Tea: Synthesis, Detection, and Anti-Alzheimer’s Disease Effect in a Transgenic Caenorhabditis elegans CL4176 Model

“…The electronic CD (ECD) spectra of (5″R)-1 and its enantiomer were calculated at the LC-wPBE/6-311G (d,p) level with Gaussian 09 software. 30 The calculation method referred to the reported article with appropriate modifications, 31 and the specific steps are shown in the Supporting Information.…”