Pierisketolide A and Pierisketones B and C, Three Diterpenes with an Unusual Carbon Skeleton from the Roots of Pieris formosa

Abstract

Pierisketolide A (1) and pierisketones B and C (2 and 3), three diterpenes with an unusual A-homo-B-nor-ent-kaurane carbon skeleton, were isolated from the roots of Pieris formosa. Their structures were characterized by a series of spectroscopic methods, X-ray diffraction, and electronic circular dichroism (ECD). Pierisketolide A (1) exhibited an analgesic effect with a 45% writhe inhibition rate at a dose of 10.0 mg/kg. The plausible biosynthetic pathways of 1-3 are proposed.

Structural Diversity and Biological Activity of the Genus Pieris Terpenoids

“…Compounds 101 – 103 , named pierisketolides A–C (Figure ), consist of an unusual A-homo-B-nor- ent -kaurane carbon skeleton with a pentacyclic 7/5/5/6/5 (pierisketolide A) and tetracyclic 7/5/6/5 (pierisketolides B and C) ring systems. All of the three compounds were isolated from the roots of P. formosa and unambiguously structurally characterized using NMR (1D and 2D) and ECD analyses and confirmed by X-ray crystallography . Biosynthetically, it was assumed that ent -kaurane precursors undergo dehydration, epoxidation, intramolecular, rearrangement, and hydroxylation to produce pierisketolides A–C.…”

“…All of the three compounds were isolated from the roots of P. formosa and unambiguously structurally characterized using NMR (1D and 2D) and ECD analyses and confirmed by X-ray crystallography. 18 Biosynthetically, it was assumed that entkaurane precursors undergo dehydration, epoxidation, intramolecular, rearrangement, and hydroxylation to produce pierisketolides A−C. Pierisketolide A exhibits an analgesic effect with a 45% writhe inhibition rate at a concentration of 10.0 mg/kg compared to blank controls, whereas none of pierisketolides A−C display cytotoxicity or neuroprotective effects at a concentration of 10 μM.…”

“…To stimulate broader interest in grayanane diterpenoids, this overview surveys and consolidates the widely scattered literature on their isolation and structural characterization. These grayanoids have specialized carbon skeletons, a 5/7/6/5 ( trans or cis / cis / cis ) ring system, which is assumed to be derived from its biogenetic precursor, ent -kaurane. − To date, nearly 200 grayanane diterpenoids belonging to 16 types of carbon skeletons have been characterized: grayanane (A-nor-B-homo ent -kaurane), 1,5- seco -grayanane, 3,4- seco -grayanane, 9,10- seco -grayanane, 1,10:2,3-disecograyanane, leucothane (A-homo-B-nor grayanane), kalmane (B-homo-C-nor grayanane), 1,5- seco -kalmane, micranthane (C-homo grayanane), mollane (C-nor-D-homo grayanane), rhodomollane (D-homo grayanane) (featuring a 5/7/6/6-fused ring system), rhodomollane (featuring a 5/7/5/5 tetracyclic system), ent -kaurane, 4,5- seco - ent -kaurane, pierisketane (A-homo-B-nor- ent -kaurane), and podocarpane . These grayanane diterpenoids originate from ent -kaurane skeleton and are thus biosynthetically related to each other (Figure ).…”

New Antifeedant Grayanane Diterpenoids from the Flowers of Pieris formosa

“…The grayanoid diterpenoids, as the characteristic secondary metabolites of the plants of Ericaceae, have attracted much attention from chemists and biologists not only for their intriguing structure but also for their diverse bioactivity, especially for their toxicity, as well as their analgesic, significant antifeedant, and insecticidal activity [ 3 , 4 , 5 ]. To date, 15 types of diterpenoid skeleton have been reported, including grayanane (A-nor-B-homo ent -kaurane) [ 5 ], 1,5-secograyanane [ 6 ], 3,4-secograyanane [ 7 ], 9,10-secograyanane [ 8 ], 1,10:2,3-disecograyanane [ 9 ], leucothane (A-homo-B-nor grayanane) [ 10 ], kalmane (B-homo-C-nor grayanane) [ 11 ], 1,5-secokalmane [ 12 ], micranthane (C-homo grayanane) [ 13 ], mollane (C-nor-D-homo grayanane) [ 14 ], rhodomollane (D-homo grayanane) [ 15 ], ent -kaurane, 4,5- seco - ent -kauran [ 16 ], pierisketane (A-homo-B-nor- ent -kaurane) [ 17 ], and rhodomollane [ 18 ]. All of these diterpenoid types are assumed to be derived biogenetically from the ent -kanrane skeleton.…”

“…The juice of both its fresh leaves and flowers are used as an insecticide and lotion for the treatment of ring worm and scabies, in folk medicine [ 19 , 20 , 21 ]. More than 60 grayanane diterpenoids with grayanane, 1,5-secograyanane, 3,4- seco -grayanane, 9,10- seco -grayanane, leucothane, 4,5- seco - ent -kauran, and pierisketane carbon skeletons have been isolated from the leaves, flowers, fruits, stems and roots of P. formosa [ 3 , 17 , 22 , 23 , 24 , 25 ]. In our previous work, two new highly esterified 3,4- seco -grayanane diterpenoids, pierisoids A and B, were reported from the flowers of P. formosa [ 20 ].…”