One-Step Semisynthesis of a Segetane Diterpenoid from a Jatrophane Precursor via a Diels–Alder Reaction

Abstract

A novel segetane diterpenoid (1) and four jatrophane diterpenoids (2-5) were isolated from an acetone extract of Euphorbia peplus. Due to quantity limitations, we prepared 1 via a Diels-Alder reaction, an approach motivated by this compound's biosynthetic pathway and successfully performed X-ray analysis of 1. Furthermore, in an in vitro activity test, 1 exhibited moderate anti-inflammatory activity, whereas both its precursor (2) and the relevant intermediate (2a, IC50 = 1.56 μM) exhibited significant anti-inflammatory activity.

Jatrophane and rearranged jatrophane-type diterpenes: biogenesis, structure, isolation, biological activity and SARs (1984–2019)

“…Unlike the aforementioned biosynthesis proposed by and previously by Jakupovic et al (1998a, b, c) that the segetane tetracyclic skeleton was formed by a two-steps cyclization of jatrophane derivative, Wan et al (2016b) found that an intermediate with four double bonds is a precursor of segetanes. Through this biosynthetic pathway, the intermediate bearing four double bonds is formed by an elimination reaction on a proper jatrophane; after that this intermediate can be transformed into a segetane via a Diels-Alder reaction in the presence of a Lewis base and/or a Lewis acid (Fig.…”

“…10). The study of the generalization of this reaction proved that the presence of a carbonyl at C-9 and lack of substitution at C-8 are indispensable to the formation of a segetane skeleton from a jatrophane skeleton (Wan et al 2016b).…”

Bioactive Segetane, Ingenane, and Jatrophane Diterpenes from Euphorbia taurinensis

“…Compound 4 was proven to be 5-acetoxy-3,9-dicinnamoyloxy-15-hydroxy-14-oxo-jatropha-6(17),11E-diene, previously described only from E. segetalis [22]. 1 Segetanes represent a peculiar and rare class of diterpenes, only 12 compounds have been described from E. paralias, E. segetalis, Euphorbia portlandica, and Euphorbia peplus, to date [21,22,24,[26][27][28][29]. According to an earlier classification, E. taurinensis and E. peplus were considered to be members of section Cymatospermum (Prokh.)…”

Helioscopianoids A–Q, bioactive jatrophane diterpenoid esters from Euphorbia helioscopia

“…, benzoyl, acetyl, nicotinoyl, butanoyl and isobutyryl). Meanwhile, jatrophanes exert a wide variety of biological activities, such as the ability to modulate of P-glycoprotein (ABCB1) 3 , 4 , 5 , 6 as well as antiproliferative 7 , 8 , antimalarial 9 , anti-inflammatory 10 , and antiviral 11 activities. From a biosynthetic perspective, jatrophanes are regarded as precursors to presegetanes, segetanes, paralianes, and pepluanes because these diterpenoids can be derived from an intramolecular cyclization of the 12-membered macrocycle of the jatrophane diterpenoids 10 , 12 , 13 .…”