Terpenes, isoprenoid

Terpenes are often referred to as isoprenoid compounds and are classified accord mg to the number of isoprene units they contain (Table 26 2)... 

Although the term terpene once referred only to hydrocarbons current usage includes functionally substituted derivatives as well grouped together under the general term isoprenoids Figure 26 6 (page 1086) presents the structural formulas for a number of representative examples The isoprene units m some of these are relatively easy to identify The three isoprene units m the sesquiterpene farnesol, for example are mdi cated as follows m color They are joined m a head to tail fashion... 

Terpenes and related isoprenoid compounds are biosynthesized from isopentenyl pyrophosphate... 

Terpenes are a large and diverse class of compounds produced by a wide variety of organisms, though plants are an especially prolific source. The terms terpenoid and isoprenoid can be used interchangeably with terpene, though, strictly, terpenes are hydrocarbons (composed only of carbon and hydrogen) while terpenoids and iso-prenoids have been further functionalized. 

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)... 

Also known as isopentyl unit. T-s3,pren. yii-nat 1 isoprenoid See terpene., T-s3- pre,n6id ... 

Wu SQ, Schalk M, Qark A, Miles RB, Coates R, Chappell J (2006) Redirection of cytoso-hc or plastidic isoprenoid precursors elevates terpene production in plants. Nat Biotechnol 24 1441-1447... 

The biosynthesis of synthetic natural rubber has been completely determined and appears in Fig. 15.1. Many plants and animals use this same biosynthetic pathway to make hundreds of terpenes and steroids from their common isoprenoid building blocks. 

Prenylation, the key step in terpene biosynthesis, is catalyzed by prenyltransferases. These enzymes are responsible for the condensation of isopentenyl pyrophosphate (IPP) with an allyl pyrophosphate, thus yielding isoprenoids. Numerous studies have been performed with fluorinated substrates in order to determine the mechanism of the reactions that involve these enzymes prenyltransferases, farnesyl diphosphate synthase (FDPSase), famesyltransferase (PFTase), and IPP isomerase. These studies are based on the potential ability of fluorine atoms to destabilize cationic intermediates, and then slow down S l type processes in these reactions. 

A high variety of isoprenoids is also observed for fossil molecules (Fig. 11.1, pink ribbon, first to the left). This suggests that the first cnidarians at Cambrian times have extensively exploited what the terpene chemistry allows (Pietra 1995). Although overshadowed by diagenetic transformations, and not comprising volatiles for obvious reasons, Chart 16.1 is suggestive of the structure of these early isoprenoids. 

A large group of isoprenoid lipids, including sterols, terpenes, and carotenoid compounds, are... 

The terpenes, carotenoids, steroids, and many other compounds arise in a direct way from the prenyl group of isopentenyl diphosphate (Fig. 22-1).16a Biosynthesis of this five-carbon branched unit from mevalonate has been discussed previously (Chapter 17, Fig. 17-19) and is briefly recapitulated in Fig. 22-1. Distinct isoenzymes of 3-hydroxy-3-methylglutaryl-CoA synthase (HMG-CoA synthase) in the liver produce HMG-CoA destined for formation of ketone bodies (Eq. 17-5) or mevalonate.7 8 A similar cytosolic enzyme is active in plants which, collectively, make more than 30,000 different isoprenoid compounds.910 However, many of these are formed by an alternative pathway that does not utilize mevalonate but starts with a thiamin diphosphate-dependent condensation of glyceraldehyde 3-phosphate with pyruvate (Figs. 22-1,22-2). 

Figure 22-2 The glyceraldehyde 3-phosphate pyruvate alternative pathway of isoprenoid biosynthesis. The intermediate 1-deoxyxylulose 5-phosphate may enter terpenes, vitamin B6, and thiamin. Isopentenyl diphosphate is shown as the final product, but the intermediate steps are uncertain. See Lange et al 2 ...

Section 26.8 X fi-Thujone a toxic monoterpene present in absinthe Terpenes and related isoprenoid compounds are biosynthesized from isopentenyl pyrophosphate. 

Until 1993, all terpenes were considered to be derived from the classical acetate/mevalonate pathway involving the condensation of three units of acetyl CoA to 3-hydroxy-3-methylglutaryl CoA, reduction of this intermediate to mevalonic acid and the conversion of the latter to the essential, biological isoprenoid unit, isopentenyl diphosphate (IPP) [17,18,15]. Recently, a totally different IPP biosynthesis was found to operate in certain eubacteria, green algae and higher plants. In this new pathway glyceradehyde-3-phosphate (GAP) and pyruvate are precursurs of isopentenyl diphosphate, but not acetyl-CoA and mevalonate [19,20]. So, an isoprene unit is derived from isopentenyl diphosphate, and can be formed via two alternative pathways, the mevalonate pathway (in eukaryotes) and the deoxyxylulose pathway in prokaryotes and plant plastids [16,19]. 

The diverse, widespread and exceedingly numerous class of natural products that are derived from a common biosynthetic pathway based on mevalonate as parent, are synonymously named terpenoids, terpenes or isoprenoids, with the important subgroup of steroids, sometimes singled out as a class in its own right. Monoterpenes, sesquiterpenes, diterpenes and triterpenes are ubiquitous in terrestrial organisms and play an essential role in life, as we know it. Although the study of terrestrial terpenes dates back to the last century, marine terpenes were not discovered until 1955. 

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). 

A number of compounds important to animal physiology have been identified as isoprenoid compounds. Notable examples are vitamin A, retinal (Section 28-7), and squalene (Table 30-1). Also, terpene hydrocarbons and oxygenated terpenes have been isolated from insects and, like famesol, show hormonal and pheromonal activity. As one example, the juvenile hormone isolated from Cecropia silk moths has the structure shown in 3 ... 

Mono- and bicyclic terpenes.1 This isoprenylsilane is useful for synthesis of mono- and bicyclic terpenes. It reacts with a variety of dienophiles under A1C13 catalysis to give mainly the so-called para adducts with the desired isoprenoid skeletons. 

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