Geranyl pyrophosphate, structure

The enzyme catalyzed reactions that lead to geraniol and farnesol (as their pyrophosphate esters) are mechanistically related to the acid catalyzed dimerization of alkenes discussed m Section 6 21 The reaction of an allylic pyrophosphate or a carbo cation with a source of rr electrons is a recurring theme m terpene biosynthesis and is invoked to explain the origin of more complicated structural types Consider for exam pie the formation of cyclic monoterpenes Neryl pyrophosphate formed by an enzyme catalyzed isomerization of the E double bond m geranyl pyrophosphate has the proper geometry to form a six membered ring via intramolecular attack of the double bond on the allylic pyrophosphate unit... 

Isoprenoid structures for carotenoids, phytol, and other terpenes start biosynthetically from acetyl coenzyme A (89) with successive additions giving mevalonate, isopentyl pyrophosphate, geranyl pyrophosphate, farnesyl pyrophosphate (from which squalene and steroids arise), with further build-up to geranyl geranyl pyrophosphate, ultimately to a- and /3-carotenes, lutein, and violaxanthin and related compounds. Aromatic hydrocarbon nuclei are biosynthesized in many instances by the shikimic acid pathway (90). More complex polycyclic aromatic compounds are synthesized by other pathways in which naphthalene dimerization is an important step (91). 

The structure of olivetol is given in the last problem and it is immediately obvious which parts of tetrahydrocannabinol (THC) come from which starting material. The only question is how do they join up There is also the question of the geometry of the alkene. It is E in geranyl pyrophosphate and that cannot cyclize. However, we know at least one way (p. 1440) - allylic rearrangement - of solving that problem. 

These unique alkaloids were obtained by Yunusov and co-workers from Haplophyllum bucharicum and appear to be derived from geranyl pyrophosphate. Although all structures have not been established, the alkaloids seem to be geranyl analogs of the Ravenia bases and are therefore considered in this section. 

Isoprene rule. In the light of the fact that the then known mono- and sesquiterpenes were built up of two or three isoprene units, respectively, O. Wallach in 1887 prtmosed his simple isoprene rule . In 1953 L. Ruzicka formulated his biogenetic isoprene rule which proved to be a milestone in the chemistry of the terpenoids. According to this rule, all terpenoids are derived from acyclic parent structures monoterpenes are formed from geranyl pyrophosphate (GPP, Cio), sesquiterpenes from famesyl pyrophosphate (FPP,... 

Cyclase preparations have been obtained which catalyze the cyclization of geranyl pyrophosphate to essentially all major structural classes of monoterpenes. These cyclases are membrane bound in the synthesizing cells, but are readily solubilized (Charlwood and Charlwood, 1991a Croteau, 1987). 

The enzyme, farnesyl pyrophosphate synthetase (prenyl transferase), is responsible for the condensation of (4.14) with (4.15) to give geranyl pyrophosphate (4.41). The same enzyme mediates addition of a further molecule of (4.14) to (4.41) yielding 2- ran5-farnesyl pyrophosphate (4.19). This is the basic unit for the elaboration of the structurally diverse sesquiterpenes. The results obtained on biosynthesis are as interesting as the sesquiterpene structures. The 2 cis... 

FIGURE 4.18. Structure of the allylic oligoisoprene pyrophosphates. DMAPP dimethyl allyl pyrophosphate, GPP geranyl pyrophosphate, FPP famesyl pyrophosphate, GGPP geranylgeranyl pyrophosphate. 

A large number of insect pheromone compounds are either simple terpenes or are derived from them. The few examples of monoterpenes given in Figure 6.4 illustrates the variety of structures that can be made from geranyl pyrophosphate or linalyl pyrophosphate without much further reaction. Both the Coleoptera and the Hymenoptera make frequent use of terpenes as secretory substances. Bark beetles have particularly employed monoterpenes in their aggregation pheromones. 

More than half of the reported secondary metabolites from macroalgae are isoprenoids. Terpenes, steroids, carotenoids, prenylated quinines, and hydroqui-nones make up the isoprenoid class, which is understood to derive from either the classical mevalonate pathway, or the mevalonate-independent pathway (Stratmann et al. 1992). Melavonic acid (MVA) (Fig. 1.2) is the first committed metabolite of the terpene pathway. Dimethylallyl (dl meth al lal) pyrophosphate (DMAPP) (Fig. 1.3) and its isomer isopentenyl pyrophosphate (IPP, Fig. 1.3) are intermediates of the MVA pathway and exist in nearly all life forms (Humphrey and Beale 2006). Geranyl (ja ran al) (C10) and famesyl (C15) units are generated by head-to-tail (Fig. 1.3) condensation of two (for C10) or three (for C15) 5-carbon DMA-like isoprene units, identifiable in final products by the characteristic fish-tail repeating units, as traced over the structure of a sesquiterpene in Fig. 1.3 (Humphrey and Beale 2006). Additional IPP condensation with famesyl pyrophosphate (FPP)... 

Continuation of the head-to-tail addition of five-carbon units to geranyl (or neryl) pyrophosphate can proceed in the same way to farnesyl pyrophosphate and so to gutta-percha (or natural rubber). At some stage, a new process must be involved because, although many isoprenoid compounds are head-to-tail type polymers of isoprene, others, such as squalene, lycopene, and /3- and y-carotene (Table 30-1), are formed differently. Squalene, for example, has a structure formed from head-to-head reductive coupling of two farnesyl pyrophosphates ... 

The pattern of labelling is consistent with the formation of these alkaloids from tryptophan (with loss of the side-chain) and geranyl-geranlol pyrophosphate. Plausible cyclizations and rearrangements of the acyclic diterpene moiety afford the above structures). 

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