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

Abstract

Chemical studies on Dichapetalum gelonioides have afforded 18 highly modified complex triterpenoids belonging to four compound classes as defined by the newly adapted functional motifs associated with the A ring...

Rearranged Dichapetalin‐Type Triterpenoids with Cytotoxic Activity from Dichapetalum gelonioides

“…Comparison of the NMR data (Table 1) indicated compound 3 possessed the same 6/6/7/5‐tetracyclic scaffold as that of 1 , and distinct NMR spectroscopic differences were observed related to the A ring and C‐17 appendages. A styrene group and a γ ‐lactone moiety of 3 as recognized by the chemical shifts and 2D NMR correlations (Figure S2A, SI) were assigned as the same as those ascribed for dichapegenin A, [ 3 ] which were attached individually to C‐3 and C‐17, based on the HMBC cross‐peaks from H 2 ‐2 to C‐1′, H‐1′ to C‐3′, and H‐20 to C‐16. Additionally, a methoxyl group was located at C‐12 by the HMBC correlation (Figure S2A, SI) of CH 3 O‐12 ( δ H 3.34)/C‐12 ( δ C 79.3).…”

“…The 2‐phenylpyran moiety as recognized based on spectroscopic data, was fused to the A ring of the molecule by the HMBC correlations of H‐2/C‐1′, H 3 ‐28/C‐29 ( δ C 73.9), and H 2 ‐29 ( δ H 3.57 and 3.83)/C‐2′ ( δ C 83.2). The γ ‐lactone moiety at C‐17 of 1 was assigned as the same as that of dichapegenin B [ 3 ] based on the closely related 1 H and 13 C NMR data and supported by the COSY and HMBC cross‐peaks (Figure 2A). Finally, the attachment of a hydroxy group at C‐7 ( δ C 73.4), C‐12 ( δ C 71.0), and C‐20 ( δ C 82.5), respectively, was deduced by the chemical shifts, which is consistent with the molecular formula.…”

“…[ 1‐2 ] Previous chemical studies on plants of Dichapetalum revealed abundant and characteristic dichapetalin‐type triterpenoids, showing potent cytotoxicity and inhibitory effects on nitric oxide production. [ 3‐7 ] Dichapetalin‐type triterpenoids possess highly modified skeletons presumably derived by condensing a C6—C2 motif to the A ring of a 13,30‐cycodammarane triterpenoid at C‐3 bearing variable C‐17 appendages. [ 3,8‐10 ] We have recently identified four classes of modified dichapetalins with potent cytotoxic activities from D. gelonioides .…”

“…[ 3‐7 ] Dichapetalin‐type triterpenoids possess highly modified skeletons presumably derived by condensing a C6—C2 motif to the A ring of a 13,30‐cycodammarane triterpenoid at C‐3 bearing variable C‐17 appendages. [ 3,8‐10 ] We have recently identified four classes of modified dichapetalins with potent cytotoxic activities from D. gelonioides . [ 3 ] Inspired by the interesting structures and distinct biological activities of dichapetalins, we thereby continued to conduct an in‐depth investigation on D. gelonioides to discover more structurally novel and bioactive molecules.…”

“…[ 3,8‐10 ] We have recently identified four classes of modified dichapetalins with potent cytotoxic activities from D. gelonioides . [ 3 ] Inspired by the interesting structures and distinct biological activities of dichapetalins, we thereby continued to conduct an in‐depth investigation on D. gelonioides to discover more structurally novel and bioactive molecules. Consequently, dichagelinoids A—E ( 1 — 5 ) (Figure 1) were isolated and characterized by solid data.…”