Rhodomicranosides A-I, analgesic diterpene glucosides with diverse carbon skeletons from Rhododendron micranthum.
Phytochemistry
; 158: 1-12, 2019 Feb.
Article
em En
| MEDLINE
| ID: mdl-30445297
ABSTRACT
Nine previously undescribed diterpene glucosides, rhodomicranosides A-I, comprising leucothane, 4,5-seco-ent-kaurane, and grayanane types, respectively, were isolated from the leaves of Rhododendron micranthum, along with seven known diterpenoids. Their structures were elucidated based on extensive spectroscopic analyses such as HRESIMS, 1D and 2D NMR, UV, and IR, and their absolute configurations were determined by various methods including X-ray diffraction analysis, electronic circular dichroism spectroscopy (ECD), calculated ECD, and Mo2(OAc)4-induced ECD, as well as chemical methods. This is the first time to report the crystal structures of leucothane diterpene glycosides. Rhodomicranosides A-C represent the first examples of 15α-hydroxy-leucothane diterpenoids, leucothane diterpene diglucosides, and 9ß-hydroxy-leucothane diterpenoids, respectively. Rhodomicranosides D and E are the second and third examples of 4,5-seco-ent-kaurane diterpenoids, and this is the first time to report 4,5-seco-ent-kaurane-type diterpenoids from the genus of Rhododendron. Rhodomicranosides F and G are the first examples of 5α-H-grayan-1(10),9(11)-diene-6-one diterpenoids. Some isolated diterpenoids were evaluated for their analgesic activity in an acetic acid-induced writhing test, and rhodomicranosides A-E and H, pierisformoside F, iso-grayanotoxin II, and grayanotoxins I, III, and IV showed significant analgesic effects with the percentage inhibitions over 50% at the dose of 1.0â¯mg/kg. In particular, grayanotoxins I and III exhibited more potent analgesic activity than morphine at a dose of 0.2â¯mg/kg, and they showed significant analgesic activity even at a lower dose of 0.04â¯mg/kg with the inhibition rates of 71.5% and 69.3%, respectively. Their preliminary structure-activity relationships were discussed.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Métodos Terapêuticos e Terapias MTCI:
Terapias_biologicas
Assunto principal:
Rhododendron
/
Diterpenos
/
Analgésicos
País/Região como assunto:
Asia
Idioma:
En
Revista:
Phytochemistry
Ano de publicação:
2019
Tipo de documento:
Article