Iron-Catalyzed Skeletal Conversion of Lathyrane to Premyrsinane Euphorbia Diterpenes and Their Cytotoxic Activities

Abstract

Two new premyrsinane-type diterpenes (2 and 3) as diastereomers were synthesized from lathyrane-type diterpene euphorbia factor L3 (1) for the first time via an efficient Fe­(acac)3-catalyzed skeleton conversion process. This conversion features a biogenetically inspired strategy that relies on a concise reductive olefin coupling involving intramolecular Michael addition with free radicals. The structures of 2 and 3 were elucidated by a combination of the interpretation of their spectroscopic data and single-crystal X-ray diffraction analysis. The premyrsinane diterpenes 2 and 3 exhibited cytotoxic activity against the 4T1 breast cancer cell line, while the parent compound euphorbia factor L3 (1) was inactive. The current results not only confirmed the biogenetic relationship between lathyranes and premyrsinanes for the first time but also suggested a novel method for the preparation of naturally rare premyrsinane diterpenes with high bioactivity from the more abundant natural lathyrane diterpenes.

Scandium-Catalyzed Skeleton Conversion of Lathyrane to Lathyranone-Type Euphorbia Diterpenes

“…Since the seminal report in 1957, α-ketol rearrangement has been gradually applied to the synthesis and structural modification of natural products. − In our continuous studies on the chemical conversion of Euphorbia diterpenes, − lathyranone A ( 1 ) together with two unnatural diterpenes ( 2 and 3 ) with the 1(15 → 14) abeo -lathyrane skeleton were obtained by treating lathyranes under a Sc­(OTf) 3 /Et 2 NH-catalyzed system (Scheme B). The present work revealed the biogenesis relationship between lathyranes and lathyranones for the first time via an efficient chemical conversion, which involved an α-ketol rearrangement leading to regeneration of the C-1–C-15 bond and the conversion of a five-member ring to the six-member ring, rather than the pinacol rearrangement of vicinal diols as mentioned in the proposal.…”

“…In biogenesis, it is generally considered that Euphorbia diterpenes originate from geranylgeranyl diphosphate; thus, many possible biosynthetic pathways have been put forward in an attempt to explain the structural interconversion among members of those skeletons. However, few studies of biogenesis relationships between different Euphorbia diterpenes have been confirmed by chemical conversion approaches. − To address this issue, more efforts focusing on the chemical mimics are needed to explore the alleged biogenetic transformation relationships.…”

New Cytotoxic Premyrsinane-Type Diterpenes from Euphorbia aleppica Against Breast Cancer Cells

“…In a study conducted by Xiao et al, two simple 3, 5, 15-trihydroxy-14oxopremyrsinane structures with three ester functions were semi-synthesized by the bioinspired Fe(acac)3catalyzed method from Euphorbia factor L3 with lathyrane structure. Premyrsinanes showed potent cytotoxic activity against the 4T1 breast cancer cell line with IC50 values of 2-8 µM (14). In the study of Hegazy et al, premyrsinanes named Euphosantianane A-D isolated from Euphorbia sanctae-catharinae with 3, 5, 7, 13, 15, 17-hexahydroxy-14-oxo-premyrsinane core structure showed moderate cytotoxicities with IC50 values of 20 to 75 µM against colon (Caco-2) and lung (A549) cancer cells (15).…”

Euphorbiaditerpenoids: isolation, structure, bioactivity, biosynthesis, and synthesis (2013–2021)

“…196 Two new premyrsinanes, 1004 and 1005 , were obtained from the chemical transformation of Euphorbia factor L 3 ( K21 ) under Fe(acac) 3 catalysis (Scheme 13). 374…”