Artemisinin: The biosynthetic pathway and its regulation in Artemisia annua, a terpenoid-rich species

Summary Artemisinin is a sesquiterpene lactone isolated from the aerial parts of Artemisia annua L. plants. Besides being currently the best therapeutic against both drug-resistant and cerebral malaria-causing strains of Plasmodium falciparum, the drug has also been shown to be effective against other infections diseases including schistosomiasis and hepatitis. More recently, it has also been shown to be effective against numerous types of tumors. Although chemical synthesis of artemisinin is possible, it is not economically feasible. The relatively low yield (0.01–0.8%) of artemisinin in A. annua is a further serious limitation to the commercialization of the drug. Therffore, the enhanced production of artemisinin either in cell/tissue culture or in the whole plant of A. annua is highly desirable. A better understanding of the biochemical pathway leading to the synthesis of artemisinin and its regulation by both exogenous and endogenous factors is essential for facilitating increased yield. Two genes of the artemisinin biosynthetic pathway have now been identified. This critical review covers recent developments related to the biosynthesis of this important compound and related terpenoids, their regulation, and the production of these compounds both in vitro and in whole plants.     

秃杉中萜类和酚类化学成分

从秃杉(Taiwania flousiana Gaussen)的根皮中分离鉴定了6个三萜类化合物、1个二萜类化合物、1个倍半萜类化合物和9个酚类化合物,其中两个为新化合物,分别鉴定为 (24S)-3b-methoxy-5a-lanost-9(11)-ene-7b, 24,25-triol(1) 和senecrassidiol-9-O-b-D-glucopyranoside (8),化合物1命名为taiwaniatriol。通过波谱学方法确定了这些化合物的结构。     

赤芝一共生菌发酵过滤液中的新倍半萜酯

从四川野生赤芝(Ganoderma lucidum (Leyss. ex Fr.) Karst.)的一共生菌Calcarisporium arbuscula Preuss的发酵过滤液中分离得到3个新的倍半萜酯类化合物,分别命名为calcarisporin B2 (1)、B3 (2)和B4 (3),通过物理方法和波谱分析确定了它们的结构.     

Rupicolin-A and -B,rupin-A and -B,and cumambrin-B oxide from Artemisia tripartita ssp. Rupicola

Five new sesquiterpene Iactones have been isolated from Artemisia tripartita Rydb. ssp. rupicola Beetle. The compounds, all guaianolides, are structurally related in what appears to be a sequence in which epoxidation plays the principal role.     

Novanin: A germacranolide from Artemisia nova

A new germacranolide, novanin (I), has been isolated from Artemisia nova and its structure determined. The compound is also present in small amount in A. tripartite Rydb. ssp. rupicola Beetle.     

Sesquiterpene lactones — insect feeding deterrents in Vernonia

Larval feeding tests were run to determine the preference of six species of Lepidoptera for two species of Vernonia which produce sesquiterpene lactones and one which has lost the ability to produce these bitter principles. Significant differences between the feeding preferences of the insect species were observed. Further feeding tests were run with a Vernonia leaf powder medium to determine how interspecific chemical differences influenced these preferences. The sesquiterpene lactone, glaucolide-A, was found to reduce larval feeding when incorporated in a Vernonia powder-agar medium. The amount of insect feeding was inversely proportional to the concentration of glaucolide-A in the medium.     

Algicidal Sesquiterpene Hydroquinones from the Brown Alga Dictyopteris undulata

Flavoglaucin, its derivatives, and pyranonigrins, which are antioxidants produced by the molds used in fermented foods, were examined for their inhibition of tumor promotion by the Epstein-Barr virus early antigen activation test. Flavoglaucin and its derivatives exhibited high activity. Flavoglaucin and such a derivative as isodihydroauroglaucin inhibited mouse skin tumor promotion in a two-stage carcinogenesis test and appear to be antitumor promoters.     

Desacetyleupaserrin and nevadensin from Helianthus pumilus

Extraction of Helianthus pumilus L. furnished the antileukemic germacradienolide desacetyleupaserrin which was isolated in crystalline form and the relatively rare flavone nevadensin (5,7-dihydroxy -6,8,4$\text{-}\text{?}$trimethoxyflavone).     

Sesquiterpene Lactones with COX‐2 Inhibition Activity from Artemisia lavandulaefolia

Two new sesquiterpene lactones, artelavanolides A ( 1 ) and B ( 2 ), and four known sesquiterpene lactones ( 3 – 6 ) were isolated from the leaves of Artemisia lavandulaefolia. Their structures were elucidated based on the analysis of spectroscopic data (1D, 2D‐NMR and HR‐ESI‐MS). The absolute configuration of 1 was determined by the analysis of single‐crystal X‐ray diffraction data. Artelavanolide A ( 1 ) is a rare sesquiterpene lactone possessing an unusual skeleton with the linkage of Me(14)–C(1) that is probably formed through a rearrangement of the guaiane‐type sesquiterpenoids. Artelavanolide B ( 2 ) is a new highly unsaturated guaianolide. Compounds 1 – 6 were tested for activities on the inhibition of COX‐2 enzyme in vitro. All of compounds exhibited inhibitory activity against COX‐2 with IC₅₀ values ranging from 43.29 to 287.07 μm compared with the positive control, celecoxib (IC₅₀ = 18.10 μm ). Among them, 3 showed the best COX‐2 inhibitory activity with an IC₅₀ value of 43.29 μm .