Grayanane Diterpenoid Glucosides from the Leaves of Rhododendron micranthum and Their Bioactivities Evaluation

Thirteen new grayanane diterpenoid glucosides, 3-epi-grayanoside B (1), micranthanosides A–E (2–6), 7α-hydroxygrayanoside C (7), micranthanoside F (8), 14β-acetyoxymicranthanoside F (9), micranthanoside G (10), 14-O-acetylmicranthanoside G (11), 14β-hydroxypieroside A (12), and micranthanoside H (13), and six known analogues (14–19) were isolated from the leaves of Rhododendron micranthum. The structures of 1–19 were elucidated based on spectroscopic analysis, comparison with literature, and chemical methods. The absolute configurations of 3-epi-grayanoside B (1) and micranthanosides A (2) and C (4) were defined by single-crystal X-ray diffraction analysis. This is the first report of the crystal structures of grayanane diterpenoid glucosides. 3-epi-Grayanoside B (1) represents the first example of a 3α-oxygrayanane diterpenoid glucoside, and micranthanosides A–D (2–5) are the first examples of 5α-hydroxy-1-βH-grayanane diterpenoids. In addition, micranthanosides C–F (4–6 and 8) and 14β-acetyoxymicranthanoside F (9) represent the first examples of grayanane glucosides with the glucosylation at C-16. All the grayanane diterpenoid glucosides 1–19 were assayed for their anti-inflammatory, antitumor, and PTP1B inhibitory activities, but did not show significant activities at 40 μM. Grayanane diterpenoid glucosides 1–18 were evaluated for their antinociceptive activity, and compounds 2, 3, 7–10, 12, 13, and 16 showed significant antinociceptive effects with percentage inhibitions in excess of 50%.