Triterpenes

Triterpenes.— Triterpenoids which have been studied include the p-bromo-benzoate derivative of cyclograndisolide (90). All four rings of this compound are trara-fused, and the presence of both the 9,19-cyclopropane 

The fact that farnesyl pyrophosphate is converted into triterpenes by tail-to-tail addition (Fig. 79) is of crucial importance. Tail refers to the pyrophosphate end. Correctly speaking, it is not two molecules of farnesyl pyrophosphate that react together but one molecule of farnesyl pyrophosphate with one molecule of nerolidyl pyrophosphate, an isomer of farnesyl pyrophosphate. The addition takes place reductively. The product is a symmetrical 30 C entity, sequalene. It is widely distributed in the plant and animal kingdoms, even though steady state concentrations may often be very small. This is what one would expect, since squalene is the 

Steroid hormones (e.g. sex hormones and hormones of the adrenal cortex) 

All of these substances have the skeletal structure of sterane or cyclo-pentoperhydrophenanthrene, which is then subjected to modifications which vary from group to group (Fig. 80). 

The sterols bear a hydroxyl group on C atom 3, which gives them their name. Of the animal sterols, the zoosterols, cholesterol is the most important. Cholesterol also occurs in plants. However, the most important sterols in higher plants are )8-sitosterol and stigmasterol (Fig. 79). They differ from each other with respect to a double bond in the side chain which is present in stigmasterol. The C skeleton of both substances consists of 29 atoms, two of which are attached as a branched chain to the side chain at C 24. This branched chain is absent from cholesterol, which has only 27 C atoms. 

In animal organisms the biosynthesis of cholesterol proceeds via the intermediate lanosterol (Fig. 79). The biosynthesis of the phytosterols, on the other hand, is not completely understood. Here, too, apparently the route via lanosterol can be adopted. However, several pieces of evidence make it seem likely that another route via cycloartenol, which is very similar to lanosterol, is practicable. The 2 C branched chain of )8-sitosterol and stigmasterol is not derived from the acetate pool, as one might have supposed. Rather, first one C is incorporated and then the second. The supplier of the 1 C units is the amino acid methionine. As usual, it participates in the reaction in the form of i -adenosyl methionine. 

5-hydride shift generates allylic cation cyclization on to this cation follows, and the cation is eventually quenched by water 

W-M rearrangement ring expansion at expense of tertiary— secondary cation 

An additional feature of the protosteryl cation is that the C-10 methyl and H-5 also share an anti-axial relationship, and are also susceptible to Wagner-Meerwein rearrangements, so that the C-9 cation formed in the cycloartenol sequence may then initiate further migrations. This can be terminated by formation of a 5,6-double 

---

The higher terpenes are formed not by successive addition of C5 units but by the coupling of simpler terpenes Thus the triterpenes (C30) are derived from two mole cules of farnesyl pyrophosphate and the tetraterpenes (C40) from two molecules of ger anylgeranyl pyrophosphate These carbon-carbon bond forming processes involve tail to tail couplings and proceed by a more complicated mechanism than that just described... 

Section 26 11 The triterpene squalene is the biosynthetic precursor to cholesterol by the pathway shown in Figure 26 10... 

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. 

Squalene is also an intermediate in the synthesis of cholesterol. StmcturaHy, chemically, and biogeneticaHy, many of the triterpenes have much in common with steroids (203). It has been verified experimentally that squalene is the precursor in the biosynthesis of all triterpenes through a series of cyclization and rearrangement reactions (203,204). Squalene is not used much in cosmetics and perfumery formulations because of its light, heat, and oxidative instabiUty however, its hydrogenated derivative, squalane, has a wide use as a fixative, a skin lubricant, and a carrier of Hpid-soluble dmgs. 

Table 51.3 and formula D show that the methyl connectivities of the CH COLOC plot are sufficient to indicate essential parts of the triterpene structure. 

Note The solvents employed should be anhydrous. The esters of phenoxy-alkanecarboxylic acids (detection limits 500 ng) [1] yield brown to violet, terpenes violet-grey [2] and triterpenes yellow to violet [5] colored chromatogram zones. 

According to Quinkert, photoexcited cyclic ketones may be transformed to open-chain unsaturated carboxylic acids in the presence of molecular oxygen. This reaction may compete efficiently with a-cleavage and secondary transformations thereof. Thus, both stereo iso meric 17-ketones (109) and (110) yield as much as 20% of the unsaturated acid (111) when irradiated in benzene under a stream of oxygen. This photolytic autoxidation has been used notably for partial syntheses of naturally occurring unsaturated 3,4-seco-acids from 3-oxo triterpenes (for references, see ref. 72). 

Squalene (Section 26.11) A naturally occurring triterpene from which steroids are biosynthesized. 

Terpenes (Section 26.7) Compounds that can be analyzed as clusters of isoprene units. Terpenes with 10 carbons are classified as monoterpenes, those with 15 are sesquiterpenes, those with 20 are diterpenes, and those with 30 are triterpenes. 

Steroids are plant and animal lipids with a characteristic tetracyclic carbon skeleton. Like the eicosanoids, steroids occur widely in body tissues and have a large variety of physiological activities. Steroids are closely related to terpenoids and arise biosynthetically from the triterpene lanosterol. Lanosterol, in turn, arises from cationic cyclization of the acyclic hydrocarbon squalene. 

The only sesquiterpenes which appear to arise by cyclization initiated by external electrophilic attack (as is common in the di-and triterpenes) are iresin (F) by attack of OH+ and polygodial (G) by attack of H+ (2,7,22,23). 

Epoxyfarnesol was first prepared by van Tamelen, Stomi, Hessler, and Schwartz 4 using essentially this procedure. It is based on the findings of van Tamelen and Curphey5 that N-bromosuccinimide in a polar solvent was a considerably more selective oxidant than others they tried. This method has been applied to produce terminally epoxidized mono-, sesqui-, di-, and triterpene systems for biosynthetic studies and bioorganic synthesis.6 It has also been applied successfully in a simple synthesis of tritium-labeled squalene [2,6,10,14,18,22-Tetracosahexaene, 2,6,10,15,19,23-hexamethyl-, (all-E)-] and squalene-2,3-oxide [Oxirane, 2,2-dimethyl-3-(3,7,12,16,20-pentamethyl-3,7,ll,-15,19-heneicosapentaenyl)-, (all-E)-],7 and in the synthesis of Cecropia juvenile hormone.8... 

Sometimes several of these rearrangements occur in one molecule, either simultaneously or in rapid succession. A spectacular example is found in the triterpene series. Friedelin is a triterpenoid ketone found in cork. Reduction gives 3p-friedelanol (47). When this compound is treated with acid, 13(18)-oleanene (48) is formed. In this case seven 1,2 shifts take place. On removal of H2O from position 3 to leave a positive charge, the following shifts occur hydride from 4 to 3 methyl... 

---