Euphnerins A and B, Diterpenoids with a 5/6/6 Rearranged Spirocyclic Carbon Skeleton from the Stems of Euphorbia neriifolia

Abstract

Euphnerins A (1) and B (2), two extremely modified diterpenoids possessing an unprecedented 5/6/6 rearranged spirocyclic carbon skeleton, and a biosynthetically related known diterpenoid (3) were purified from the stems of Euphorbia neriifolia. Their structures were identified by NMR experiments and X-ray diffraction analysis, as well as experimental and calculated electronic circular dichroism data comparison. A putative biosynthetic relationship of 1 and 2 with their presumed precursor 3 is proposed. Compound 1 showed NO inhibitory effects in lipopolysaccharide-stimulated BV-2 cells with an IC50 value of 22.4 μM.

Euphorbia Diterpenes: An Update of Isolation, Structure, Pharmacological Activities and Structure–Activity Relationship

“…Within the review period, over 200 different polycyclic diterpenes were described, including abietanes ( 1 – 5 ) [ 38 , 68 ], atisane ( 6 ) [ 35 ], cembranes ( 7 – 9 ) [ 33 , 44 ]; ent -abietanes ( 10 – 28 ) [ 34 , 38 , 47 , 59 ], ent -atisanes ( 29 – 41 ) [ 32 , 33 ], ent -labdanes ( 68 – 72 ) [ 38 , 51 ], ent -isopimaranes ( 42 – 64 ) [ 43 , 45 , 69 , 70 ], ent -kauranes ( 65 – 67 ) [ 33 ], ent -rosanes ( 73 – 87 ) [ 45 , 46 , 71 ], gaditanone ( 88 ) [ 27 ], and kaurane ( 247 ) [ 31 , 66 ]. Atisanes and cembranes were the least dominant subclasses, as only one new atisane, atisane-3-oxo-16 α ,17-diol ( 6 ) [ 35 ], from E. kansuensis and three cembranes diterpenes, euphopane C ( 7 ) from E. pekinensis [ 44 ], euphoroylean A ( 8 ), and B ( 9 ) from E. royleana [ 33 ], were isolated.…”

“…Furthermore, an unusual tetracyclic diterpenoid named eupholathone ( 343 ) [ 66 ] was isolated from E. lathyris and described for the first time in the genus. Besides, previously undescribed euphnerin A ( 337 ) and euphnerin B ( 338 ) [ 71 ] isolated from the stems of E. neriifolia were found to possess a spirocyclic carbon skeleton rarely found among rosane diterpenoids. This was proposed to be occasioned by rearrangement reactions.…”

“…This was proposed to be occasioned by rearrangement reactions. Interestingly, euphominoid E ( 73 ) [ 71 ], isolated from the same species, was found to co-occur with euphnerin A ( 337 ) [ 71 ] and euphnerin B ( 338 ) [ 71 ] as they had the same B/C ring systems. Based on the observations, euphominoid E ( 73 ) was postulated to be the precursor for the biosynthesis of euphnerin A ( 337 ) and euphnerin B ( 338 ) [ 71 ].…”

“…Various reports have demonstrated the potential of naturally occurring labdanes diterpenoids as NF-κB, nitric oxide (NO), or arachidonic acid (AA) modulators as summarized in a review article published by Tran et al [ 95 ]. Chemical investigation of E. neriifolia led to the isolation of ent -rosane diterpenoids, euphominoid E ( 73 ) [ 71 ], while studies on E. hylonoma afforded ent-rosa-1(10), 15-dien-2-one ( 74 ) [ 45 ]. Others included euphominoid A–L ( 75 – 87 ) isolated from E. milii [ 46 ].…”

“…Rosane diterpenoids, such as 18-hydroxyhugorosenone, were previously isolated from E. ebracteolata. Li et al [ 48 ] reported the isolation of rosane diterpenoids; ebraphenol A–D ( 332-335 ) and ebralactone A ( 336 ) for the first time from the root extracts of E. ebracteolate, while Du et al [ 71 ] isolated euphnerin A ( 337 ) and B ( 338 ) from stem extracts of E. neriifolia.…”