Myrsinane-Type Diterpenes: A Comprehensive Review on Structural Diversity, Chemistry and Biological Activities

Abstract

Euphorbia species are important sources of polycyclic and macrocyclic diterpenes, which have been the focus of natural-product-based drug research due to their relevant biological properties, including anticancer, multidrug resistance reversal, antiviral, and anti-inflammatory activities. Premyrsinane, cyclomyrsinane, and myrsinane diterpenes are generally and collectively designated as myrsinane-type diterpenes. These compounds are derived from the macrocyclic lathyrane structure and are characterized by having highly oxygenated rearranged polycyclic systems. This review aims to describe and summarize the distribution and diversity of 220 myrsinane-type diterpenes isolated in the last four decades from about 20 Euphorbia species. Some myrsinane diterpenes obtained from Jatropha curcas are also described. Discussion on their plausible biosynthetic pathways is presented, as well as isolation procedures and structural elucidation using nuclear magnetic resonance spectroscopy. Furthermore, the most important biological activities are highlighted, which include cytotoxic and immunomodulatory activities, the modulation of efflux pumps, the neuroprotective effects, and the inhibition of enzymes such as urease, HIV-1 reverse transcriptase, and prolyl endopeptidase, among other biological effects.

A Biomimetic Approach to Premyrsinane-Type Diterpenoids: Exploring Microbial Transformation to Enhance Their Chemical Diversity

“…Interestingly, the reaction occurred with high regio- and diastereoselectivity ( Scheme 3 ). Contrary to the Fe-mediated cyclization of Euphorbia factor L 3 [ 21 ], premyrsinane 5 was obtained at room temperature as only one diastereoisomer, with the same stereochemistry at C-6, C-12, and C-13 than most naturally occurring premyrsinane-type diterpenoids [ 10 ]. Our newly developed protocol would represent the first report of a biomimetic cyclization of a 6,17-epoxylathyrane into premyrsinane derivative.…”

“…To the best of our knowledge, this strategy has not been used for the functionalization of non-activated positions of premyrsinane-type diterpenoids. Studies of the biological activities of premyrsinanes are scarce in the literature; this is likely because of the reduced amount of the isolated compounds [10]. Nevertheless, several studies have reported that premyrsinanes possess promising anticancer [17][18][19], multidrug resistance reversal [20], and anti-inflammatory activities, inhibiting the lipopolysaccharideinduced NO production [21].…”

“…Premyrsinanes-type diterpenoids have been isolated from approximately 20 Euphorbia species and Jatropha jurcus [ 10 ]. They are characterized by a 5/7/6/3-tetracyclic carbon framework with trans -oriented A/B and B/C ring junctions.…”

“…They are characterized by a 5/7/6/3-tetracyclic carbon framework with trans -oriented A/B and B/C ring junctions. As described in several reports, they often exhibit three characteristic oxymethyne protons at C-3, C-5, and C-7 positions and one oxygenated methylene group at C-17 [ 10 , 11 ].…”

“…Appendino et al proposed a biogenetic relationship between lathyranes and premyrsinanes based on the cooccurrence of these diterpenoids with a similar functionalization pattern (Scheme 1). They Studies of the biological activities of premyrsinanes are scarce in the literature; this is likely because of the reduced amount of the isolated compounds [10]. Nevertheless, several studies have reported that premyrsinanes possess promising anticancer [17][18][19], multidrug resistance reversal [20], and anti-inflammatory activities, inhibiting the lipopolysaccharide-induced NO production [21].…”