Diterpenoids pyrophosphate

The terpenoid precursor isopentenyl diphosphate, formerly called isopentenyl pyrophosphate and abbreviated IPP, is biosynthesized by two different pathways depending on the organism and the structure of the final product. In animals and higher plants, sesquiterpenoids and triterpenoids arise primarily from the mevalonate pathway, whereas monoterpenoids, diterpenoids, and tetraterpenoids are biosynthesized by the 1-deoxyxylulose 5-phosphate (DXP) pathway. In bacteria,... 

A useful review of diterpenoid chemistry has appeared.1 Some aspects of the distribution of diterpenoids in plants have been discussed.2 An interesting feature of the new diterpenoids described over the past few years is the increase in the number with skeleta based on the macrocyclic ring formed by the cyclization of geranylgeranyl pyrophosphate at the distal double bond. This mode of cyclization has formed the basis of a biogenetically patterned synthesis3 of ( )-nephthenol (2) and ( )-cembrene A from the distal epoxide of geranylgeranyl phenyl thioether (1). 

In a biogenetically patterned synthesis, the cyclization of epoxygeranylgeraniol with boron trifluoride etherate has been shown to afford the compounds (103) and the pimaradienols (104). The cyclization of epoxygeranylgeranyl pyrophosphate by kaurene synthetase affords the epimeric 3-hydroxykaurenes. A cyclization of olefinic jS-keto-esters (105) to the bicyclic compound (106) has formedthe basis of a novel synthesis of A -podocarpen-13-one (107), a compound which is an intermediate in several diterpenoid total syntheses. Synthetic approaches to the... 

The kaurene synthetase from Echinocystsis macrocarpa (wild cucumber) seed is able to cyclize both R- and 5-enantiomers of 14,15-oxidogeranylgeranyl pyrophosphate to give 3a- and 3/3-hydroxykaurene respectively in good yields. The degree of flexibility of substrate revealed by the diterpenoid cyclase makes more plausible previous proposals that naturally occurring axially hydroxylated terpenoids might arise by direct cyclization of appropriate epoxide precursors. 

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... 

Cubitene (95), which was isolated from an East African termite soldier, Cubitermes umbratus, possesses an unusual twelve-membered ring. Its structure was determined by A-ray analysis. The irregular isoprenoid structure may be derived via a cembrene derivative or by coupling farnesyl pyrophosphate with dimethylallyl pyrophosphate to give an irregular diterpenoid directly. 

Generally, terpenoids have been believed to be biosynthesized via acetate-mevalonate pathway. Aphidicolin, a tetracyclic diterpenoid isolated from moulds, Cephalosporium aphidicola [47] and Nigrospora sphaerica [48], was also proved to be biosynthesized from mevanonic acid [49]. In this pathway, isopentenyl pyrophosphate (IPP), geranylgeranyl diphosphate (GGPP), labdane-type and pimarane-type diterpenoids were proposed to be intermediate precursors of aphidicolin [50]. 

The diterpenoids are a large and ubiquitous family of isoprenoids derived from 2E,61% ] 0 -geranylgeranvl pyrophosphate. Of all the families of natural products, the diterpenoids have one of the widest ranges of biological activity. The clearest classification of the cyclic diterpenoids (abietane, labdane, clerodane,...) is based on biogenetic considerations. The variety of structural types found amongst the diterpenoids has led to their use as phytochemical markers. Indeed, many of the diterpenoids found in recent years have been isolated in the course of phytochemical surveys of the Compositae. 

An unusual diterpenoid, cyathin A3 (121). has been isolated from the bird s nest fungus, Cyathus helenae. Its structure, which followed from a careful examination of the n.m.r. spectrum supported by an X-ray analysis, represents a unique cyclization and rearrangement of geranylgeranyl pyrophosphate (122). 

There have been a number of novel diterpenoid skeleta described during the year based on alternative modes of discharge of the carbocation derived from the initial cyclizations of geranylgeranyl pyrophosphate. Diterpenoids of different skeletal types appear to be characteristic taxonomic markers in a current survey of the Compositae. The useful Kyoto series of reviews of diterpenoid chemistry has been continued. ... 

Fig. 111. Synthesis of cyclic diterpenoids from (+)-labdadienyl pyrophosphate...

Terpenes are synthesised in organisms by complex mechanisms from isoprene units, isopentenyl phosphate and dimethy-lallyl diphosphate (pyrophosphate). The first product is geranyl diphosphate, which is the universal precursor of monoterpenoids. The reaction of geranyl diphosphate with another molecule of isopentenyl diphosphate yields famesyl diphosphate, which is the precursor of sesquiterpenoids. Further reaction with isopentenyl diphosphate gives geranylgeranyl diphosphate, the precursor of diterpenoids (see Figure 3.10). 

Diterpenoids contain four isoprene units and the natural precursor for them all is geranylgeranyl pyrophosphate. The potential variety of diterpenoids is even greater than that of sesquiterpenoids and, as with the latter, many of them possess interesting biological activities. As a result of their low volatility and consequent lack of odor, there are no diterpenoids that are used in perfumery, other than as solvents and diluents. 

Fifteen terpenoid antibiotics are included in this chapter two additional ones are discussed elsewhere in this book (mycelianamide and fumagiUin). All these substances contain carbon, hydrogen, and at least two oxygens. All are either monoterpenoids (comprised of two Cg units), sesquiterpenoids (three Cg units), or triterpenoids (six Cg units). Since most of the terpenoids are of these three types, this is hardly surprising a few diterpenoid (four Cg units) and carotenoid (eight Cg units) antibiotics will probably eventually be found. In some of the terpenoid antibiotics (e.g. grifohn and eburicoic acid), carbon atoms not derived from isopentenyl pyrophosphate (I) have become attached to terpenoid units in others (e.g. helvoHc acid and pristimerin), carbon atoms have been lost at some stage in the biosynthesis. 

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