Dimericursones A and B: two unprecedented hexacyclic dimeric diterpenoids from the root barks of Jatropha curcas

Abstract

Dimericursones A and B (1 and 2), two unprecedented hexacyclic dimeric diterpenoids, were obtained from the root barks of Jatropha curcas. Their structures were elucidated by extensive spectroscopic analysis, electronic circular dichroism calculations, and single-crystal X-ray diffraction. Dimericursone B (2) showed significant inhibition on nitric oxide production of lipopolysaccharide-induced RAW264.7 macrophages with IC50 values of 5.65 μM.

Highly Oxygenated Dimeric Grayanane Diterpenoids as Analgesics: TRPV1 and TRPA1 Dual Antagonists from Rhododendron molle

“…Diterpenoid dimers are composed of two homo‐ or hetero‐ monomeric diterpenoids linked through ether bonds, ester bonds, C—C carbon bonds, or ring moieties. [ 1 ] Dimeric diterpenoids are relatively rare in nature and were mainly reported from higher plants of Acanthaceae, [ 2 ] Annonaceae, [ 3 ] Asteraceae, [ 4 ] Calceolariaceae, [ 5 ] Chrysobalanaceae, [ 6 ] Cupressaceae, [ 7 ] Ebenaceae, [ 8 ] Ericaceae, [ 9 ] Euphorbiaceae, [ 10 ] Fabaceae, [ 11 ] Icacinaceae, [ 12 ] Lamiaceae, [ 13 ] Liliaceae, [ 14 ] Meliaceae, [ 15 ] Rhizophoraceae, [ 16 ] Sapindaceae, [ 17 ] Scapaniaceae, [ 18 ] Selaginellaceae, [ 19 ] Taxaceae, [ 20 ] Velloziaceae, [ 21 ] and Zingiberaceae. [ 22 ] Some of them exhibited significant anti‐inflammatory, [ 10 ] cytotoxic, [ 7 ] antiviral, [ 17 ] antimalarial, [ 15 ] and antibacterial activities.…”

Total Synthesis and Target Identification of the Curcusone Diterpenes

“…We then set out to synthesize dimericursone A (2a ) from 1a – 1d via a biomimetic dimerization. The proposed biosynthesis of 2a consists of a sequence of oxidative dehydrogenation of 1 a /1b or dehydration of 1c / 1d to form a reactive cyclopentadienone intermediate followed by Diels–Alder dimerization and cheletropic extrusion of carbon monoxide . From there, 2a could be converted to 2b via another oxidative dehydrogenation and double bond isomerization.…”

“…In summary, we completed the first asymmetric total synthesis and target identification of the curcusone natural products. Our convergent synthesis builds upon a cheap and abundant chiral pool molecule (8) and features a thermal [3,3]-sigmatropic rearrangement and an FeCl 3 -promoted global hydrolysis/aldol condensation cascade to rapidly construct the critical cycloheptadienone core. This efficient synthetic route yielded curcusones A and B (1a and 1b) in only 9 steps, curcusones C and D (1c and 1d) in 10 steps, and dimericursone A (2a) in 12 steps from (S)-(−)-8.…”

“…Since then, around 30 curcusone molecules have been isolated including curcusones F–J, which lack the dienone moiety in the seven-membered ring. Structurally rearranged analogs like spirocurcasone ( 3 ) and dimeric analogs such as dimericursone A ( 2a ) and dimericursone B ( 2b ) were discovered recently. , Among them, curcusones A–D ( 1a – 1d ) exhibited low micromolar IC 50 values against a broad spectrum of human cancer cell lines . However, no total syntheses of curcusones A–D ( 1a – 1d ) and their dimeric products ( 2a and 2b ) were reported, prior to this study, and their mode of action remained unknown.…”

Biogenetic and biomimetic synthesis of natural bisditerpenoids: hypothesis and practices

“…The DA cycloaddition between monomers curcusone A and B, abundant components in J. curcas, could be the key reactions in the biosynthetic routes for 71 and 72, together with dehydrogenation and dehydration (Scheme 4). 49 2.1.2 Bisditerpenoids from hetero-Diels-Alder reactions. The DA reactions can also be applied to unsaturated systems involving heteroatoms, mostly a,b-unsaturated ketones and carbonyls in natural products, which are known as hetero-Diels-Alder (HDA) reactions.…”