Cephalodiones A–D: Compound Characterization and Semisynthesis by [6+6] Cycloaddition

Abstract

Cephalodiones A–D (1–4), the first example of C19‐norditerpenoid dimers, were isolated and fully characterized from a Cephalotaxus plant. These new skeletal natural products shared a unique tricyclo[6.4.1.12,7]tetradeca‐3,5,9,11‐tetraene‐13,14‐dione core that was capped in both ends with rigid multicyclic ring systems either C2‐symmetrically or asymmetrically. Compounds 1–4 were proposed to be biosynthetically produced by the [6+6]‐cycloaddition of two identical C19‐norditerpenoid troponoids, which was validated by the semisyntheses of dimers 2–4. Moreover, some compounds showed significant inhibition on Th17 cell differentiation.

Discovery of four modified classes of triterpenoids delineated a metabolic cascade: compound characterization and biomimetic synthesis

“…[3][4][5][6][7] In addition to discovering structurally interesting and biologically significant natural molecules, [8][9][10][11][12][13][14][15] we have been committed to the biomimetic and/or bioinspired syntheses of important natural compounds identified by our research group as well, which aimed to validate the proposed biosynthetic pathways from chemical view. [16][17][18][19] Dichapetalin-type triterpenoids, a rare category of natural products featuring the modified skeletons by condensing a C6-C2 unit to the A ring of 13,30-cycodammarane triterpenoids, were found as the characteristic components of Dichapetalum and Phyllanthus genera. [20][21][22][23][24][25][26][27][28][29][30][31][32] The typical dichapetalin-type triterpenoids possess a common 2-phenylpyran moiety fused to the A ring of 13,30-cycodammarane triterpenoids, with the major differences being the C-17 side chain and oxidation patterns.…”

Cephalotane‐Type Norditerpenoids from Cephalotaxus fortunei var. alpina

“…70 derivatives comprising six types of rearranged carbon skeletons were reported successively, [ 9 ] some of which exhibited potent anti‐inflammatory activities [ 5 ] and inhibition of the NF‐κB signaling pathway, [ 5,10 ] and have garnered a fair amount of attention from the synthetic community. [ 11‐17 ] As part of our continuing search for structurally intriguing and/or biologically significant cephalotane diterpenoids/norditerpenoids from Cephalotaxus species, [ 8,10,18‐21 ] nine new cephalotane‐type norditerpenoids ( 1 — 9 ) and two known analogues ( 10 and 11 ) (Figure 1) were isolated from the seeds of C. fortunei var. alpina .…”

Recent Advances in the Total Synthesis of Cephalotane-Type Norditerpenoids from Cephalotaxus sinensis

“…alpine in 2021 by Yue. 25 Cephalotanin A showed inhibition of NF- κ B (IC 50 = 4.12 ± 0.61 μmol·L –1 ). 5 As shown in Figure 3 , the common feature of the cephalotane-type skeleton comprises a cage-like structure of six rings consisting of a four-ring carbon skeleton (rings A/B/C/D) and a bridged lactone unit (E ring).…”