Squalene 29 yields

Species Sex No. of Samples Total No. of Dogfish Sampled Oil Yield (g/IOOg Liver) Squalene Yield (g/IOOg Oil) ... 

Squalene is a naturally occurring triterpene and the precursor of steroids [66]. Oxidation (via squalene monooxygenase) of one of the terminal double bonds of squalene yields 2,3-squalene oxide, which undergoes enzyme-catalyzed cyclization to afford lanosterol, which is then elaborated into cholesterol and other steroids. Humans cannot live without squalene, because squalene is regarded as an essential building block for the production of hormones and other important substances in the human body. Squalene in olive oil may contribute to the low cholesterol levels of individuals consuming Mediterranean-style diets [67]. 

The achiral triene chain of (a//-rrans-)-3-demethyl-famesic ester as well as its (6-cis-)-isoiner cyclize in the presence of acids to give the decalol derivative with four chirai centres whose relative configuration is well defined (P.A. Stadler, 1957 A. Escherunoser, 1959 W.S. Johnson, 1968, 1976). A monocyclic diene is formed as an intermediate (G. Stork, 1955). With more complicated 1,5-polyenes, such as squalene, oily mixtures of various cycliz-ation products are obtained. The 18,19-glycol of squalene 2,3-oxide, however, cyclized in modest yield with picric acid catalysis to give a complex tetracyclic natural product with nine chiral centres. Picric acid acts as a protic acid of medium strength whose conjugated base is non-nucleophilic. Such acids activate oxygen functions selectively (K.B. Sharpless, 1970). 

IPP react with each other, releasiag pyrophosphate to form another allyl pyrophosphate containing 10 carbon atoms. The chain can successively build up by five-carbon units to yield polyisoprenes by head-to-tad condensations alternatively, tad-to-tad condensations of two units can yield squalene, a precursor of sterols. Similar condensation of two C2Q units yields phytoene, a precursor of carotenoids. This information is expected to help ia the development of genetic methods to control the hydrocarbon stmctures and yields. 

Steroids are heavily modified triterpenoids that are biosynthesized in living organisms from farnesyl diphosphate (Cl5) by a reductive dimerization to the acyclic hydrocarbon squalene (C30), which is converted into lanosterol (Figure 27.12). Further rearrangements and degradations then take place to yield various steroids. The conversion of squalene to lanosterol is among the most... 

Other evidence for the wrong value of the very high yield of double-bond destruction can be found from the lower G(-double bond) found by Turner111 and Turner and coworkers112 in the case of irradiation of squalene and natural rubber. 

The tetracyclic alcohol 179 is produced by the action of boron trifluoride etherate or tin(IV) chloride on the oxirane 178 (equation 85)95. A similar cyclization of the oxirane 180 yields DL-<5-amyrin (181) (equation 86)96. In the SnCLt-catalysed ring-closure of the tetraene 182 to the all-fraws-tetracycle 183 (equation 87) seven asymmetric centres are created, yet only two of sixty-four possible racemates are formed97. It has been proposed that multiple ring-closures of this kind form the basis of the biosynthesis of steroids and tetra-and pentacyclic triterpenoids, the Stork-Eschenmoser hypothesis 98,99. Such biomimetic polyene cyclizations, e.g. the formation of lanosterol from squalene (equation 88), have been reviewed69,70. 

Cholesterol is one of the isoprenoids, synthesis of which starts from acetyl CoA (see p. 52). In a long and complex reaction chain, the C27 sterol is built up from C2 components. The biosynthesis of cholesterol can be divided into four sections. In the first (1), mevalonate, a Ce compound, arises from three molecules of acetyl CoA. In the second part (2), mevalonate is converted into isopen-tenyl diphosphate, the active isoprene. In the third part (3), six of these C5 molecules are linked to produce squalene, a C30 compound. Finally, squalene undergoes cycliza-tion, with three C atoms being removed, to yield cholesterol (4). The illustration only shows the most important intermediates in biosynthesis. 

Formation of squalene. Isopentenyl diphosphate undergoes isomerization to form dimethylallyl diphosphate. The two C5 molecules condense to yield geranyl diphosphate, and the addition of another isopentenyl diphosphate produces farnesyl diphosphate. This can then undergo dimerization, in a head-to-head reaction, to yield squalene. Farnesyl diphosphate is also the starting-point for other polyisoprenoids, such as doli-chol (see p. 230) and ubiquinone (see p. 52). 

Formation of cholesterol. Squalene, a linear isoprenoid, is cyclized, with O2 being consumed, to form lanosterol, a C30 sterol. Three methyl groups are cleaved from this in the subsequent reaction steps, to yield the end product cholesterol. Some of these reactions are catalyzed by cytochrome P450 systems (see p. 318). 

This enzyme [EC 2.5.1.21], also known as farnesyltransf-erase, presqualene di-diphosphate synthase, and squa-lene synthase, catalyzes the condensation of two molecules of farnesyl diphosphate to form presqualene diphosphate and diphosphate (or, pyrophosphate). The entire enzyme complex catalyzes the NADPH-depen-dent reduction of presqualene diphosphate to yield squalene. 

The methylene chloride soluble portion of a methanol extract from the wood of Eury-coma longifolia shows strong cytotoxic properties. One of the active constituents, longi-lene peroxide (77) (P2i, 0—0 = 1.472 A, Figure 31), was isolated in a 0.0003% yield. The characteristic horse-shoe-like arrangement, which is observed in the crystal structure of squalene derivative 77, has been associated with its biological activity ... 

H. S. Olcott (University of California, Berkeley, Calif.) We have studied the effects of aliphatic amines on the autoxidation of a fish oil and squalene in air at moderate temperatures. There was little protection unless phenolic-type inhibitors were also added, in which case secondary amines were more effective than primary or secondary amines. However, at 70 °C. trioctylamine alone protected the fish oil, whereas at lower temperatures it did not (2). Further study revealed that peroxides react with trioctylamine to yield some dioctylhydroxylamine which has antioxidant properties (1). These and other observations (3) indicate that... 

Cholesterol is the sterol characteristic of animal cells plants, fungi, and protists make other, closely related sterols instead. They use the same synthetic pathway as far as squalene 2,3-epoxide, at which point the pathways diverge slightly, yielding other sterols, such as stigmasterol in many plants and ergosterol in fungi (Fig. 21-37). 

Cholesterol is formed from acetyl-CoA in a complex series of reactions, through the intermediates /3-hydroxy-/3-methylglutaryl-CoA, mevalonate, and two activated isoprenes, dimethylallyl pyrophosphate and isopentenyl pyrophosphate. Condensation of isoprene units produces the noncyclic squalene, which is cyclized to yield the steroid ring system and side chain. 

On treating the anion generated from 2-farnesylthiothiazoline (603) with farnesyl bromide a 44% yield of the squalene derivative (605) was produced. Desulfurization of this intermediate with Raney nickel afforded squalene in 80% yield (Scheme 133). 

The biosynthesis of steroids begins with the conversion of three molecules of acetyl-CoA into mevalon-ate, the decarboxylation of mevalonate, and its conversion to isopentenyl pyrophosphate. Six molecules of isopentenyl pyrophosphate are polymerized into squalene, which is cyclized to yield lanosterol. Lanos-terol is converted to cholesterol, which is the precursor of bile acids and steroid hormones. 

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