Diterpenoid biosynthesis

Dawson, R.M., Godfrey, I.M., Hogg, R.W.. and Knox, J.R., Synthetic routes to some isotopically labelled intermediates for diterpenoid biosynthesis. Aust. J. Chem., 42, 561, 1989. 

A review of diterpenoid biosynthesis has been published. Preliminary results are reported on the biosynthesis of crassin acetate (57a). Another cyclotetrade-cane terpenoid, casbene is formed from geranylgeranyl pyrophosphate (6 n = 3) in Ricinus communis. The enzymes involved have been partially separated. Although a wide range of diterpenoids are formed from copalyl... 

Diterpenoids are derived biosynthetically from geranylgeranyl diphosphate (GGPP), which is itself biosynthesized by reaction of farnesvl diphosphate with isopentenyl diphosphate. Show the structure of GGPP, and propose a mechanism for its biosynthesis horn FPP and IPP. 

The typical secondary metabolites of soft corals are diterpenoids, although some species also produce sesquiterpenoids. The sesquiterpene portion of furoquinol (Structure 2.102) is labeled by [2-3H]mevalonolactone in Sinularia capillosa,m while Heteroxenia sp. converts acetate and meva-lonate into cubebol (Structure 2.103) and clavukerin A (Structure 2.104).188 In contrast, acetate is used for cetyl palmitate synthesis in Alcyonium molle, but not for de novo diterpene biosynthesis.188... 

Vakognavine is the first example of an N, C-19-seco-diterpenoid alkaloid reported and an interesting alkaloid for biogenetic speculation. The authors (116) suggested that the C-19 aldehyde may be a plausible alternate to the pseudokobusine structure as an intermediate in the biosynthesis of the modified atisine-type skeletons such as hetisine. The C-19 hydroxyl of vakognavine hydriodide (119) is reminiscent of the oxazolidine oxygen of isoatisine. 

Fuscoside B is a lobane diterpenoid isolated from the Caribbean gorgonian Eunicea fusca. It has been evaluated for the inhibitory activities against COX-1, 5-LOX, 12-LOX, PLA2, and other eicosanoid biosynthesis pathways and found only to irreversibly inhibit the 5-LOX pathway with an IC50 value of 10 pM. [141,142]... 

Plant products have also been detected in non-plant organisms. Morphine 1, the archetypal plant alkaloid, has in fact been shown to be a physiological plasma constituent and its production in mammals could be traced to the liver expression of the critical enzymes of its biosynthesis.17 In addition, the plant hormone abscisic acid 12 has been detected as an endogenous constituent of human brain,18 while caffeine 13 was isolated from a marine gorgonian (Paramuricea chamaelon)19 and the atisane diterpenoid serofendic acid 14, an inhibitor of the oxidant-induced mitochondrial death pathway and putative activator of mitoK(ATP) channels, has been characterised from foetal calf serum.20... 

Figure 3. Carbon-carbon bonds introduced from synthetic building blocks by Nicolaou et al. (A) and Danishefsky et al. (B, C2-C9 broken after ketene cycloaddition). In the putative biosynthesis of the diterpenoid 4,7-oxaeunicellanes from cembranoid precursors, only one additional carbon-carbon bond (Cl-CIO) would have to be formed (C). (1 R1 = (E)-N(6 )-methyluroca-nyl, R2 = beta-D-0(2)-acetylarabinopyranosyl stereochemistry has been omitted for clarity).

In conclusion, three independent syntheses of marine eunicellane diterpenoids have been developed, which will be the basis of the future development of this exciting natural product class. The biosynthesis of the eunicellanes probably involves the oxidative cyclization of a cembranoid precursor lacking solely the bond between Cl and CIO (C, Fig. 3). Considering the number of carbon - carbon bonds formed in the course of... 

The partial synthesis from epicandicandiol of some C- and H-labelled kaurene derivatives has been described.These have possible application in the study of the biosynthesis of the Isodon diterpenoids. The syntheses of [17- C]kaur-16-en-20-ol from enmein and of 3-oxygenated derivatives of [17- C]kaur-16-ene from ent-3jS,19-dihydroxy-kaur-16-ene have also been described. The synthesis of radioactive aphidicolin has also been reported. It has been shown ° that ent-kaur-15-ene is formed by the dwarf mutant (ds) of maize in place of ent-kaur-16-ene. 

Peters RJ. Uncovering the complex metabolic network underlying diterpenoid phytoalexin biosynthesis in rice and other cereal crop plants. Phytochemistry 2006 67 2307-2317. 

Terpenoids, which are also known as isoprenoids, constitute the most abundant and structurally diverse group of plant secondary metabolites, consisting of more than 40,000 different chemical structures. The isoprenoid biosynthetic pathway generates both primary and secondary metabolites that are of great importance to plant growth and survival. Among the primary metabolites produced by this pathway are phytohormones, such as gibberellic acid (GA), abscisic acid (ABA), and cytokinins the carotenoids, such as chlorophylls and plastoquinones involved in photosynthesis the ubiquinones required for respiration and the sterols that influence membrane stmcture (see also Steroid and Triterpene Biosynthesis) (Fig. 1). Monoterpenoids (CIO), sesquiterpenoids (Cl5), diterpenoids (C20), and... 

Figure 1 Schematic overview of the biosynthesis of the monoterpenoids, sesquiterpenoids, diterpenoids, and triterpenoids. Representatives of these classes with biological relevance are shown. Enzymatic steps are indicated in italics DMADP, dimethylallyl diphosphate CDP, geranyl diphosphate GGDP, geranylgeranyl diphosphate FDP, farnesyl diphosphate IDP, isopentenyl diphosphate.

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