Biosynthesis of diterpenes

The biosynthesis of diterpenes was created to produce molecular diversity. Literally hundreds of different macrocyclic, bicyclic and polycyclic diterpenes... 

Two major steps exist in the biosynthesis of diterpene resin acids the formation of the diterpene and the stepwise oxidation of the diterpene to the corresponding acid. Most conifer diterpenes are tricyclic they are biosynthesized by bifunctional di-TPS that first cyclize geranylgeranyl diphosphate to (+)-copalyl diphosphate and then cyclize this intermediate even... 

Three modified clerodanes 9, 10 and 11 were extracted from Dodonaea viscosa. These compounds have been proposed as hypothetical intermediates in the biosynthesis of diterpenes containing bicyclo[5.4.0]undecane or bicyclo[5.3.0]decane ring systems <01T2981>. Three furoclerodanes, namely 12-epi-Teukotschyn, teughrebin and 12-epi-... 

West CA( 1981) Biosynthesis of diterpenes. In Porter JW, Spurgeon SL (eds) Biosynthesis of isoprenoid compoimds. Wiley, New York, Vol 1, p 375... 

Diterpenes are a heterogeneous class of natural compounds based on 20 carbon atoms. They are widely distributed in nature, both in terrestrial and marine organisms, and originate by condensation of four isoprene units derived from mevalonate or deoxyxylulose phosphate [1] pathways, wherein the latter pathway was recently discovered taking place in the biosynthesis of diterpene compounds in plants [2]. As for other classes of natural compounds diterpenes have shown an importance as biomarker of certain species, thus contributing to their chemotaxonomy classification [3]. For example, macrocyclic diterpenes and their cyclization products have been isolated only from Euphorbiae plants of which they could be considered as biomarker [4]. Although thousands of diterpene compounds have been described in nature from terrestrial and marine organisms, only few of them became clinically effective [5]. Active compounds isolated from plants are used directly in therapy or... 

BIOSYNTHESIS OF DITERPENE PHYTOALEXIN PRECURSORS IN CELL-FREE EXTRACTS OF RICE... 

UV-treated rice leaves have a greatly increased capacity for biosynthesis of diterpenes in comparison with untreated controls. Among the dlterpene hydrocarbon products, ent-kaurene, a gibberllin precursor, and sandaracopimaradiene, a proposed precursor of the oryzalexin group of phyto-alexins, have been identified by GC-MS analysis. Three other metabolites tentatively identified as plmaradlenes were also detected. 

Diterpenes are among the most abundant terpenoids on the planet. Although significant advancements have been made, the biosynthesis of diterpenes is not fully elucidated. In this chapter, a general overview of the biosynthesis of diterpenes and selected applications of pericyclic reactions for the synthesis of complex diterpenes will be presented. 

BIOSYNTHESIS OF DITERPENES BASED ON CATIONIC CYCLIZATIONS, 1,2-SHIFTS,... 

Since GAs as diterpenes share many intermediates in the biosynthetic steps leading to other terpenoids, eg, cytokinins, ABA, sterols, and carotenoids, inhibitors of the mevalonate (MVA) pathway of terpene synthesis also inhibit GA synthesis (57). Biosynthesis of GAs progresses in three stages, ie, formation of / Akaurene from MVA, oxidation of /-kaurene to GA 2" hyde, and further oxidation of the GA22-aldehyde to form the different GAs more than 70 different GAs have been identified. 

Davis EM, Croteau R (2000) Cyclization Enzymes in the Biosynthesis of Monoterpenes, Sesquiterpenes and Diterpenes. 209 53-95 Davies JA, see Schwert DD (2002) 221 165-200... 

A recent example demonstrates that corals rely on induced biosynthesis of terpenes as a dynamic defense strategy as well. The induction of terpenoid secondary metabolites was observed in the sea whip Pseudopterogorgia elisabethae [162]. Levels of pseudopterosins 89-92, a group of diterpene glycosides with anti-inflammatory and analgesic properties (Scheme 23) [163-165], are increased in response predation by the mollusk Cyphoma gibbosum. First bioassays indicate that these natural products are involved in the chemical defense. 

The biosynthesis of monoterpenes, the major components of peppermint essential oils, can be divided into four stages (Fig. 9.4). Stage 1 includes the formation of isopentenyl diphosphate (IPP) and dimethylallyl alcohol (DMAPP). In plants, two separate pathways are utilized for the synthesis of these universal C5 intermediates, with the cytosolic mevalonate pathway being responsible for the formation of sterols and certain sesquiterpenes, and the plastidial mevalonate-independent pathway being involved in the biosynthesis of isoprene, monoterpenes, certain sesquiterpenes, diterpenes, tetraterpenes, as well as the side chains of chlorophyll and plastoquinone.16 In peppermint oil gland secretory cells, however, the mevalonate pathway is blocked and the biosynthesis of monoterpenoid essential... 

Davis EM, Croteau R, Leeper FJ, Vederas JC (2000) Cyclization enzymes in the biosynthesis of monoterpenes, sesquiterpenes, and diterpenes. In Topics in current chemistry biosynthesis-aromatic polyketides, isoprenoids, alkaloids. Springer, Heidelberg, pp 53-95... 

These processes are normally enzyme-catalyzed. Purefy ctemical processes are seldom encountered with carbon conq)ounds in nature. The few exceptions include the very act of phenol coupling (by which racemic compounds are obtained), cyclization reactions ofpolyprenyl compoimds (which benefit from the preferred conformation of the reaction partners, suitable for the cyclization, Wendt 2000), and Diels-Alder cycloadditions. The latter have been advocated for the biosynthesis of celastroidine A (= volubilide) from a lupane triterpene and an abietane diterpene in two different plants, Hippocratea celastroides Kunth from Mexico (Jimenez-Estrada 2000) and Hippocratea volubilis Linnaeus (Alvarenga 2000). 

The mevalonate-independent pathway is present in most bacteria and all phototropic organisms. In higher plants and most algae both pathways run independently. The mevalonate pathway is located in the cytoplasm and is responsible for the biosynthesis of most sesquiterpenoids. The mevalonate-independent pathway, in contrast, is restricted to the chloroplasts where plastid-related isoprenoids such as monoterpenes and diterpenes are biosynthesised via this pathway [43-45]. Figure 4.2 illustrates the interrelationships of both biosynthetic pathways connected to Fig. 4.1 [46]. 

---