Open-chain 1,5-polyenes (e.g. squalene) and some oxygenated derivatives are the biochemical precursors of cyclic terpenoids (e.g. steroids, carotenoids). The enzymic cyclization of squalene 2,3-oxide, which has one chiral carbon atom, to produce lanosterol introduces seven chiral centres in one totally stereoselective reaction. As a result, organic chemists have tried to ascertain, whether squalene or related olefinic systems could be induced to undergo similar stereoselective cyclizations in the absence of enzymes (W.S. Johnson, 1968, 1976).  [c.90]

Lanosterol is one component of lanolin a mixture of many substances that coats the wool of sheep  [c.1094]

How does the tetracyclic steroid cholesterol arise from the acyclic triterpene squa lene" It begins with the epoxidation of squalene described earlier m Section 16 14 and continues from that point m Figure 26 10 Step 1 is an enzyme catalyzed electrophilic ring opening of squalene 2 3 epoxide Epoxide ring opening triggers a series of carbo cation reactions These carbocation processes involve cyclization via carbon-carbon bond formation (step 1) ring expansion via a carbocation rearrangement (step 2) another cyclization (step 3) followed by a cascade of methyl group migrations and hydride shifts (step 4) The result of all these steps is the tetracyclic triterpene lanosterol Step 5 of Figure 26 10 summarizes the numerous remaining transformations by which lanosterol IS converted to cholesterol  [c.1094]

The conversion of lanosterol to cholesterol involves 19 steps and is described in the article Cholesterol Biosynthesis Lanosterol to Cholesterol on pp 377-384 in the March 2002 issue of the Journal of Chemical Education  [c.1095]

Inhibitors of Sterol Biosynthesis. The discovery of compounds that inhibit ergosterol biosynthesis in fungi was one of the most significant advances in the history of fungicide research (34). Sterols are known to be essential for all eukaryotes, either synthesized de novo from acetate or taken up from the environment. In fungi, the eady steps in the pathway from acetate culminate with the cyclization of squalene epoxide to produce lanosterol [79-63-0] (47), C qH qO. Figure 5 presents the steps involved in the biosynthesis of the principal sterol in most fungi, ergosterol [57-87-4] (33),  [c.107]

Other, removable cation-stabilizing auxiliaries have been investigated for polyene cyclizations. For example, a sdyl-assisted carbocation cyclization has been used in an efficient total synthesis of lanosterol. The key step, treatment of (257) with methyl aluminum chloride in methylene chloride at —78° C, followed by acylation and chromatographic separation, affords (258) in 55% yield (two steps). When this cyclization was attempted on similar compounds that did not contain the C7P-silicon substituent, no tetracycHc products were observed. Steroid (258) is converted to lanosterol (77) in three additional chemical steps (225).  [c.442]

Triterpenes. The triterpenes (30 carbon atoms) are widely found in nature, especially plants, both in the free state and as esters or glycosides. A smaller but important group, including lanosterol [79-63-0] (114), occurs in animals. The triterpene hydrocarbon, squalene [111-02-4] (115), occurs in the hver oils of certain fish, especially those of sharks.  [c.431]

Nomenclature. The Vitamin D compounds ate steroidal materials and thus ate named according to the lUPAC-IUB rules for nomenclature (1) (Table 1). Vitamin [520-91 -2] is a mixture of vitamin D2 and lumisterol.  [c.124]

Lanosterol is one component of lanolin, a mixture of many substances that coats the wool of sheep.  [c.1094]

The conversion of lanosterol to cholesterol involves 19 steps and is described in the article "Cholesterol Biosynthesis Lanosterol to Cholesterol" on pp. 377-384 in the March, 2002 issue of the Journal of Chemical Education.  [c.1095]

FIGURE 8.17 Many monoterpenes are readily recognized by their characteristic flavors or odors (limonene in lemons citronellal in roses, geraniums, and some perfumes pinene in turpentine and menthol from peppermint, used in cough drops and nasal inhalers). The diterpenes, which are C90 terpenes, include retinal (the essential light-absorbing pigment in rhodopsin, the photoreceptor protein of the eye), phytol (a constituent of chlorophyll), and the gibberellins (potent plant hormones). The triterpene lanosterol is a constituent of wool fat. Lycopene is a carotenoid found in ripe fruit, especially tomatoes.  [c.252]

Conversion of Lanosterol to Cholesterol Requires 20 Additional Steps  [c.840]

FIGURE 26 10 The biosyn thetic conversion of squa lene to cholesterol proceeds through lanosterol Lano sterol IS formed by enzyme catalyzed cyclization of the 2 3 epoxide of squalene  [c.1094]

The irradiation pathway of precalciferol [50524-96-4] (18) is shown in Figure 3. When irradiated, ergosterol (15b) first undergoes a photochemically allowed conrotatory ring opening of the B-ring to form (18) as a central intermediate. Triene (precalciferol) (18) can undergo a thermally allowed 1,7-sigmatropic shift to form vitamin D2. Precalciferol also forms tachysterol [115-61 -7] (19) by photochemical isomerization of the central triene double bond and lumisterol [474-69-1] (20) by conrotatory ring closure (30—33). Although a tme steady state of the photochemical reaction is never achieved owing to the formation of over-irradiated products, the experimentally determined quasistationary-state yields are ia good agreement with the calculated steady-state values (34,35).  [c.416]

Vitamin D. The irradiation of the provitamins to produce vitamin D as well as several isomeric substances was first studied with ergosterol. The chemistry is identical for the vitamin series and yields analogous isomers. In 1932, a scheme for the irradiation of ergosterol leading to vitamin D2 was proposed (45). Twenty years later, the mechanism of the irradiation of the provitamins to vitamin D and its photoisomers was further elucidated (46,47). More recendy, Jacobs (48) has reviewed the photochemistry. A number of products associated with the irradiation process are shown ia Figure 3. The geometry and electronic characteristics of these molecules have been well estabUshed by x-ray crystallographic analysis and valence force-field calculations (50—52). The irradiation process, which converts 7-dehydrocholesterol to vitamin D also occurs ia the skin of animals if sufficient sunlight is available. The photochemical and thermal isomerisations occur duting the generation of vitamin D in vivo as well as duting its synthetic photochemical preparation (24,53,54). The initial step iavolves ring opening of the B-ring of the sterol by ultraviolet activation of the conjugated diene. The absorbance of uv energy activates the molecule, and the tt — tt excitation (absorption, 250—310 nm = 291 nm, e = 12, 000) results ia the opening of the 9,10 bond and the formation of the (Z)-hexadiene, previtamiu (R) [1173-13-3] (17) or previtamiu D2 (R ) [21307-015-1] (18). The uv irradiation of 7-dehydrocholesterol or ergosterol results ia the steady diminution ia concentration of the provitamin, initially giving rise to predominantiy previtamin D. The pre- levels reach a maximum as the provitamin level drops below ca 10%. The concentration of the previtamin then falls as it is converted to tachysterol and lumisterol, which iacrease ia concentration with continued irradiation (see Fig. 4). Temperature, frequency of light, time of irradiation, and concentration of substrate all affect the ratio of products. Previtamin D undergoes thermal equiUbration to vitamin D (2) or (4), <7 -vitamin D2 [50-14-6] and (7 -vitamin [67-97-0], respectively. The conversion of previtamin D (18) or (17) at temperatures of <80° C by thermal isomerisation to give the cis  [c.128]

Fig. 4. Time course for uv-irradiation of 7-dehydtocholesterol ( ) (o), previtamin D (x), lumisterol (-), tachysterol. Fig. 4. Time course for uv-irradiation of 7-dehydtocholesterol ( ) (o), previtamin D (x), lumisterol (-), tachysterol.
Additionally, the tt — tt excitation of previtamin D can result ia ring closure back to the provitamin (1) [57-87-4] or (3) [434-16-2] or to lumisterol2 [474-69-1] (19) or lumisterol [5226-01 -7] (20), which have the 9 p,10 a configuration. This excitation can also exhibit (Z) (E) photoisomerization to the 6,7-(T)-isomer, tachysterol2 [115-61 -7] (21) or tachysterol [63902-44-3] (22) (58,52).  [c.130]

The alcohol fraction is likewise a complex mixture of both aUphatic and cycHc compounds (Table 10). The principal components are cholesterol (34%), and lanosterol and dihydrolanosterol (38%). The aUphatic alcohols account for about 22% of the unsaponifiable products. Sixty-nine components of ahphatic alcohols had been reported up to 1974 (latest reported work as of ca 1997). The hydrocarbons (ca 0.5%) show stmctural similarity to the wool—wax acids or ahphatic alcohols and contain highly branched alkanes as well as cycloalkanes.  [c.354]

Lanosterol [79-63-0] M 426.7, m 138-140", [a] d +<52.0" (c 1, CHCI3). Recrystd from anhydrous MeOH. Dried in vacuo over P2O5 for 3h at 90°. Purity checked by proton magnetic resonance.  [c.277]

FIGURE 26.10 The biosynthetic conversion of squa-lene to cholesterol proceeds through lanosterol. Lano-sterol is formed by enzyme-catalyzed cyclization of the 2,3-epoxide of squalene.  [c.1094]

The terpenes are a class of lipids formed from combinations of two or more molecules of 2-methyl-l,3-butadiene, better known as isoprene (a five-carbon unit that is abbreviated C5). A monoterpene (Cjo) consists of two isoprene units, a sesquiterpene (C15) consists of three isoprene units, a diterpene (C20) has four isoprene units, and so on. Isoprene units can be linked in terpenes to form straight chain or cyclic molecules, and the usual method of linking isoprene units is head to tail (Figure 8.16). Monoterpenes occur in all higher plants, while sesquiterpenes and diterpenes are less widely known. Several examples of these classes of terpenes are shown in Figure 8.17. The triterpenes are C30 terpenes and include squalene and lanosterol, two of the precursors of cholesterol and other steroids (discussed later). Tetraterpenes (C40) are less common but include the carotenoids, a class of colorful photosynthetic pigments. /3-Carotene is the precursor of vitamin A, while lycopene, similar to /3-carotene but lacking the cyclopentene rings, is a pigment found in tomatoes.  [c.251]

Squalene monooxygenase, an enzyme bound to the endoplasmic reticulum, converts squalene to squalene-2,3-epoxide (Figure 25.35). This reaction employs FAD and NADPH as coenzymes and requires Og as well as a cytosolic protein called soluble protein activator. A second ER membrane enzyme, 2,3-oxidosqualene lanosterol cyclase, catalyzes the second reaction, which involves a succession of 1,2 shifts of hydride ions and methyl groups.  [c.838]

Although lanosterol may appear similar to cholesterol in structure, another 20 steps are required to convert lanosterol to cholesterol (Figure 25.35). The enzymes responsible for this are all associated with the endoplasmic reticulum. The primary pathway involves 7-dehydroeholesterol as the penultimate intermediate. An alternative pathway, also composed of many steps, produces the intermediate desmosterol. Reduction of the double bond at C-24 yields cholesterol. Cholesterol esters—a principal form of circulating cholesterol—are synthesized by acyl-CoA cholesterol acyltransferases (ACAT) on the cytoplasmic face of the endoplasmic reticulum.  [c.840]

Condensation of the lynestrol intermediate (47) with ethyl-magnesium bromide affords the oral androgen ethylestrenol (72) Animal experiments on the various drugs above have all shown increased anabolic effects relative to androgenicity.  [c.170]

Allylic bromination of pregnenolone acetate with dibromodi-methylhydantoin affords the 7-bromo compound (155) of undefined stereochemistry. Dehydrobromination by means of collidine followed by saponification affords the 5,7 endocyclic cis,cis-diene, 156. This compound contains the same chromophore as ergosterol, a steroid used as a vitamin D precursor. The latter displays a complex series of photochemical reactions among the known products is lumisterol, in which the stereochemistry at both C9 and Cio is inverted. Indeed, irradiation of 156 proceeds to give just such a product (158). This reaction can be rationalized by  [c.184]

See pages that mention the term Lynestrol : [c.96]    [c.234]    [c.234]    [c.407]    [c.1095]    [c.551]    [c.551]    [c.580]    [c.554]    [c.108]    [c.421]    [c.426]    [c.427]    [c.131]    [c.355]    [c.254]    [c.119]    [c.695]    [c.416]    [c.1094]    [c.1095]    [c.252]    [c.838]    [c.166]   
The organic chemistry of drug synthesis Vol.1 (1977) -- [ c.166 , c.186 ]