Antimalarial diterpenoid dimers of a new carbon skeleton from Aphanamixis grandifolia

Abstract

Chemical investigation into the minor constituents of Aphanamixis grandifolia yielded three new diterpenoid dimers, aphadilactones E-G (1-3) featuring a new carbon skeleton. Their structures and absolute configurations were fully established by comprehensive spectroscopic data analysis and ECD calculation. Discovery of another two new dimers (4 and 5) suggested the structure of recently reported aphanamene A to be re-investigated. Compounds 1-5 showed moderate antimalarial activities with low micromolar IC50 values.

Naturally Occurring Diterpenoid Dimers: Source, Biosynthesis, Chemistry and Bioactivities

“…Chiral HPLC dramatically accelerated the isolation of stereoisomers, especially those with complex structures like diterpenoid dimers [7][8][9]. In recent years, ECD calculations have been widely used to determine the absolute configurations of diterpenoid dimers [7,[9][10][11]. According to our literature review, around 31 publications related to diterpenoid dimers were found before 2000, and this number has increased to 88 in January 2016.…”

“…Furthermore, the development of purification and structural elucidation methods, especially preparative HPLC and high resolution NMR, makes it now possible to identify compounds at trace amounts. Chiral HPLC dramatically accelerated the isolation of stereoisomers, especially those with complex structures like diterpenoid dimers [7][8][9]. In recent years, ECD calculations have been widely used to determine the absolute configurations of diterpenoid dimers [7,[9][10][11].…”

“…Phytochemical studies of the green fruits of X. amazonica and stem barks and leaves of X. frutescens resulted in the identification of amazonins B and A (6, 10) and frutoic acid (7), respectively [26,27]. In other studies, emarginatines A-D (8,9,11,12) were isolated from the branches and stem barks of X. emarginata [26,28]. These dimers are composed of kauranoid and labdanoid units, and could be considered as taxonomic markers of the genus Xylopia.…”

“…These two compounds inhibited LPS-induced NO production in RAW264.7 cells with IC 50 values of 9.72 and 7.98 µM, respectively. Recently, a chemical investigation into the minor constituents of A. grandifolia yielded one diterpenoid dimer, namely aphadilactone I (159), which was found to be a diastereoisomer of aphanamene A [9]. Besides, three diastereomeric diterpenoid dimers, namely aphadilactones E-G (160-162), were also isolated from this species and found to contain a new carbon skeleton incorporating a 1,1,2,2-tetrasubstituted cyclobutane moiety.…”

Natural Products Research in China From 2015 to 2016

“…Annotinolides A–C ( 671 - 673 ), three novel 7,8-seco-lycopodanoid 8,5-lactones, were afforded by Lycopodium annotinum (Tang et al, 2016b ). Aphanamixis grandifolia (Hainan, China) produced three novel diterpenoids dimers, aphadilactones E–G ( 674 - 676 ) (Zhang et al, 2016b ). Artaboterpenoid A ( 677 ) and (±)-artaboterpenoid B ((±)- 678 ), two new bisabolene-derived sesquiterpenoids, were obtained from the roots of Artabotrys hexapetalus (Xi et al, 2016 ).…”