Terpenes squalene

Chain elongation during polymerization of prenyl units can be terminated in one of a number of ways. The pyrophosphate group may be hydrolyzed to a monophosphate or to a free alcohol. Alternatively, two polyprenyl compounds may join "head to head" to form a symmetric dimer. The C30 terpene squalene, the precursor to cholesterol, arises in this way from two molecules of famesyl diphosphate as does phy-toene, precursor of the Qo carotenoids, from E,E,E geranylgeranyl diphosphate. The phytanyl groups of archaebacterial lipids (p. 385) arise rather directly from geranylgeranyl diphosphate by transfer of the poly-... 

Plant terpenes may deter herbivores and attract pollinators. They may participate in competition among plants and may act as antibiotics, called phytoalexins, to protect plants from bacteria and fungi.84 In invertebrate animals terpenes serve as hormones, pheromones, and defensive repellants (Figs. 22-3,22-4). The terpene squalene is the precursor to sterols. Some terpenes are toxic. For example, thujone (Fig. 22-3), which is present in the liqueur absinthe, causes serious chronic poison-... 

Natural rubber (pages 5 and 6) is a member of this group of polymers although it is synthesised in the rubber tree by a quite different process. NR is a high member of the terpene family and is made by the same kind of enzyme-controlled chemistry as the terpene squalene, which is the precursor of cholesterol in animals. Squalene is often used as a low Mj model to study the reactions of cis-poly(isoprene) (PI). 

Although it has 27 carbon atoms (instead of 30) and is therefore not strictly a terpene, cholesterol Is synthesized in the body from the terpene squalene through a complex process that, in its final stages, involves the loss of three carbon atoms. 

Tail to tail linkages of isoprene units sometimes occur especially m the higher terpenes The C(12)—C(13) bond of squalene unites two C15 units m a tail to tail man ner Notice however that isoprene units are joined head to tail within each C15 unit of squalene... 

Processes of this kind are important in the biosynthesis of steroids and tetra- and pentacyclic terpenes. For example, squalene 2,3-oxide is converted by enzymatic catalysis to dammaradienol. 

Polyene cyclizations are of substantial value in the synthesis of polycyclic terpene natural products. These syntheses resemble the processes by which the polycyclic compounds are assembled in nature. The most dramatic example of biosynthesis of a polycyclic skeleton from a polyene intermediate is the conversion of squalene oxide to the steroid lanosterol. In the biological reaction, an enzyme not only to induces the cationic cyclization but also holds the substrate in a conformation corresponding to stereochemistry of the polycyclic product.17 In this case, the cyclization is terminated by a series of rearrangements. 

Examples of terpenes (a) isoprene, (b) phytene, which is a side chain of chlorophyll a, (c) squalene, (d) vitamin A, (e) haslene, (f) amyrin, and (g) cephalosporin. 

Squalene takes part in metabolism as precursor for synthesis of steroids and structurally quite similar to (3-carotene, coenzyme qlO, vitamins Ki, E, and D. The squalene in skin and fat tissue comes from endogenous cholesterol synthesis as well as dietary resources in people who consume high amounts of olive and fish oil especially shark liver (Gershbein and Singh, 1969). Squalene is synthesized by squalene synthase which converts two units of farnesyl pyrophosphate, direct precursor for terpenes and steroids, into squalene. As a secosteroid, vitamin D biosynthesis is also regulated by squalene. Moreover, being precursor for each steroid family makes squalene a crucial component of the body. 

A well-known phase which is used as a reference because it is the only one that is well defined is squalane. Its polarity is zero by the McReynolds scale (2.13). This saturated hydrocarbon (C3oHe2) is derived from squalene, a natural terpene extracted from shark liver or skin. On this stationary phase, which can be used between 20 and 120 C (deposition or impregnation), compounds are eluted... 

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 ... 

Since squalene can be produced from farnesyl pyrophosphate with NADPH and a suitable enzyme system, the general features of the above scheme for terpene biosynthesis are well supported by experiment. 

Daphniphyllum macropodum contains a great variety of related alkaloids whose structures are quite complex and novel (Section II). It is structurally evident that these alkaloids with an isopropyl or a potential isopropyl group are regarded as a terpene alkaloid. Bio-genetieally, these Daphniphyllum alkaloids, particularly C22 alkaloids, have been proposed to be derived from four molecules of mevalonic acid (MVA) and one acetate unit (15, 39). However, the recent tracer experiments showed that these alkaloids could be biosynthesized from six MVA molecules through a squalene-like intermediate. Accordingly, they should be included in a group of triterpene alkaloid. 

Most oils contain low levels of saturated and unsaturated hydrocarbons. In olive oil, the unsaturated hydrocarbon squalene can constitute up to 40% of the unsaponifiable fraction (Boskou, 1996). Other hydrocarbons commonly present in olive oil are straight chain alkanes and alkenes with 13 to 35 carbon atoms, along with very low amounts of branched chain hydrocarbons. Variations are found between different olive varieties but the main hydrocarbons are those with 23, 25, 27 and 29 carbon atoms (Guinda et al., 1996). Olive oil can clearly be differentiated from other vegetable oils on the basis of hydrocarbon components, and levels of 2.6% crude rapeseed oil or crude sunflower oil can be detected by hydrocarbon analysis (Webster et al., 1999). Terpenes have been identified in the volatile fraction of crude sunflower oil (Bocci and Frega, 1996). 

The Opening of Squalene-2,3-Epoxide Steroids are tetracyclic compounds that serve a wide variety of biological functions, including hormones (sex hormones), emulsifiers (bile acids), and membrane components (cholesterol). The biosynthesis of steroids is believed to involve an acid-catalyzed opening of squalene-2,3-epoxide (Figure 14-6). Squalene is a member of the class of natural products called terpenes (see Section 25-8). The enzyme squalene epoxidase oxidizes squalene to the epoxide,... 

Although related structurally to phenanthrene, these compounds are not acetogenins but are true terpenes that are synthesized in living systems from isoprene via squalene. (Compare the structure of squalene—compound 6 in Example 6.1—with that of perhydrocyclopentanophenanthrene.)... 

---