Diverse Chemosensitizing 8,9-Secolindenane-Type Sesquiterpenoid Oligomers and Monomers from Sarcandra glabra

Abstract

The theoretical analysis and biomimetic conversion confirmed that the oxidative cleavage of the Δ 8,9 double bond of chloranthalactone A (I), an abundant lindenane-type sesquiterpenoid in Chloranthaceae plants, generates 8,9secolindenane (II) with active aldehyde and maleic anhydride fragments that can capture other fragments and produce oligomeric molecules. A careful phytochemical investigation of the leaves of Sarcandra glabra led to the discovery of eight novel 8,9-secolindenane-type sesquiterpenoid oligomers (sarglalactones A−H, compounds 1−8), including three unprecedented trimers (1−3), five unusual dimers (4−8), and five 8,9-secolindenane monomers (sarglalactones I−M, 9−13). Their structures were determined by comprehensive HRMS, NMR, circular dichroism, and X-ray diffraction analyses. Bioassay results showed that these oligomers significantly reversed the multidrug resistance of MCF-7/doxorubicin (DOX) cells and increased the sensitivity of U2 OS cells to DOX by downregulating the HMGB1 expression.

Sarcaglarols A—D, Lindenane−Monoterpene Heterodimers from Sarcandra glabra Based on Molecular Networks

“…with petroleum ether, and CH 2 Cl 2 , successively. Based on the results of preliminary experiments and HPLC spectrum, combined with the isolation process of our previous research on the leaves of S. glabra , [ 8 ] the portion of petroleum ether and CH 2 Cl 2 was subjected to silica gel column chromatography to yield three fractions (Fr. a—c) and five fractions (Fr.…”

“…The discovery of sarcaglarols A—D ( 1 — 4 ) allowed us to reconsider our previously proposed biogenetic pathways of this unique lindenane‐monoterpene heterodimeric skeleton fused by a 1,2‐dioxane moiety. [ 6 ] According to their structures and recent references, [ 23‐25 ] geraniol and chloranthalactone A, the abundant constituents in S. glabra , [ 8 ] would be the biogenetic precursors, and photocatalytic aerobic [2+2+2] cycloaddition may play the key role in construction of this unique skeleton. A modified biosynthetic pathway of this heterodimeric skeleton was proposed in Scheme 1.…”

“…Lindenane sesquiterpenes dimers (LSDs) are a group of biologically active natural products and are considered to be the characteristic chemical constituents of Chloranthaceae family. [ 1‐4 ] In addition to the LSDs constructed by two homologous monomers in various ways, [ 5‐8 ] only a few dimers composed of a lindenane and another substructure derived from different biosynthetic pathways have been reported, such as heterodimers assembled by lindenane with eudesmane, [ 9 ] aromadendrane, [ 10 ] monoterpene and normonoterpene. [ 6,11 ] The complex molecular architecture and appealing bioactivities of these heteropolymers have attracted our great interests.…”

Spirolindemers A and B, Lindenane Sesquiterpenoid Oligomers Equipped with Oxaspiro[4.5]decane from Chloranthus henryi

“…[ 1 ] Their structural diversities are normally expanded by the intermolecular Diels‐Alder reaction between Δ 15(4),5(6) and Δ 8′(9′) , which was the most common pattern for dimerization, [ 3‐4 ] and subsequent skeletal rearrangement, [ 5‐6 ] oxidation, and acylation. [ 7‐9 ] To date, LDS oligomers with significant bioactivities [ 1a,2,6 ] have attracted much attention from researchers on the discovery and synthesis of these natural products. [ 2 ] Particularly, the inflammatory potency of the dimers reported by us previously, such as shizukaol D, can be as an attractive therapeutic candidate for inflammatory diseases.…”

“…In our previous phytochemical researches on the LDS oligomers from Chloranthaceae plants, several kinds of novel dimeric and trimeric oligomers have been discovered. [ 3,7,10‐13 ] According to their interesting biogenetic pathway, it is worthwhile and expectable to explore naturally‐occurring unique polymeric skeletons based on LDS units. Thus, Chloranthus henryi , a famous medicinal plant for the treatment of traumatic injuries, rheumatic arthralgia, fractures, pulmonary tuberculosis, and neurasthenia in southwestern China, [ 14 ] was selected as our research objective to discover novel LDS oligomers.…”