Triterpenes and Steroids

There has been considerable discussion regarding the mode of action of the sea cucumber and starfish saponins. Both the triterpene and steroidal glycosides inhibit both Na/K ATPase and Ca/Mg ATPase 06) possibly as a result of their aglycone structures. However, their detergent properties cause membrane disruption which will influence the activity of membrane-bound enzymes such as the ATPases. In investigating the actions of saponins on multilamellar liposomes, it was found that cholesterol serves as the binding site for such saponins and that cholesterol-free lip-somes are not lysed by saponins 107). 

The biomimetic cationic domino cyclization of an acyclic unsaturated substrate to give the tetracyclic scaffold of triterpenes and steroids is intensively described in the literature.1121 The concept has recently been used by Corey et al. to prepare enanti-opure (+)-dammarenediol II 18 in an exceptional short way.1131 The synthesis demonstrates the power of the combination of cation-olefin polyannulation with the aldol cyclization for tetraannulation (scheme 4). Successive treatment of the acylsilane 13 with 2-propenyllithium 14 and the iodoalkane 15 efficiently yidds the epoxytriene 16. The Lewis acid... 

Concerning the metabolism of triterpenes and steroids, quite a number of P450 catalyzed transformations are very important, namely the 14a-demethyla-tion of lanosterol [50], the side-chain cleavage of cholesterol [51]and pregnenes [52], and the desaturation of ring A of androgens with concomitant oxidative removal of C(19) [53]. The latter reaction is catalyzed by human placental aromatase, associated with a NADPH-dependent reductase, and requires three moles of oxygen and three moles of NADPH in order to oxidize andro-stenedione 45 to formic acid and estrone 46, Fig. 10. 

If as above we simply represent alicyclic rings sharing two Gs by a vertical line, then we can represent the basic tetracyclic structure of lanosterol as G61G61 G6 C5 (noting that there are two double bonds and various alkyl substituents and also a 3-hydroxyl on the first of the alicyclic rings). Many subsequent reactions yield cholesterol, a major triterpene membrane component that modifies the fluidity of animal cell membranes and is a precursor for synthesis of animal bile acids (fat solubilizing amphipathic detergents) plant triterpenes and steroid hormones such as the corticosteroids cortisol and cortisone, the mineralocorticoid aldosterone and the sex hormones testosterone and 17-(3-oestradiol. The structure and bioactivity of the plant terpenes is sketched below. 

Two molecules of farnesyl pyrophosphate are converted to squalene, a C30 triterpene. Squalene is the starting material for all triterpenes and steroids. 

Indole, Triterpene, and Steroidal Alkaloids , Verlag Chemie, Weinheim, 1975. 

Biosynthetically-patterned microbiological transformations exploit the substrate flexibility of enzymes involved in the biosynthesis of secondary metabohtes. These biotransformations are sometimes known as analogue biosynthesis or precursor-directed biosynthesis. This approach to biotransformation can be useful in preparing analogues of biologically-active microbial metabolites for structure-activity studies, a feature that has been exploited with penicillins using a cloned isopenicillin N synthase. The structures of the substances that are transformed and of their products can also shed light on the stereo-electronic constraints of enzymatic steps and on the nature of biosynthetic intermediates, a feature that has been exploited in studies on the cyclization of squalene to the triterpenes and steroids. 

The integrity of biomembranes is of ultimate importance for the functioning of cells and of all neuronal activities. Compounds which disturb biomembranes and thus make cells leaky, are usually strong cell poisons and interfere with membrane potential. Natural products which exhibit these properties are either very lipophilic or amphiphilic, such as mono-, sesqui- and diterpenes or triterpene and steroid saponins, respectively. 

Terpenoids occur in abundance in the plant world where they possess many different kinds of functions. Essentially, they are derived from the basic 5-carbon isoprene unit, biosynthetically as isopentenyl pyrophosphate, which is itself derived from acetate via mevalonic acid. They may be classified into diverse groups according to the number of isoprene units, e.g., monoterpenes (Cio), sesquiterpenes (Cu), diterpenes (C2o), triterpenes and steroids (C30),... 

There are different types of tests for detecting the presence of triterpenes in an extract. The Liebermann-Bouchard reagent is the one most frequent used to differentiate triterpenes and steroidal aglycones, whereas Zimmermann s test is appropriate for 3-oxo triterpenoids. 

Triterpenic and steroidal compounds were also isolated from Teucrium species. Common triterpenic acids such as ursolic acid, oleanolic acid and small amounts of micromeric acid were isolated from T.fruticans [81] while a-amyrin, lupeol, sitosterol and stigmasterol were present in T. divaricatum subsp. villosum [75]. Two new steroidal compounds SP-hydroxy-stigmast-24(24i), 25-dien-242-al (157) and 3P-hydroxy-24a-ethylcholesta-5, 25-dien-7-one (158) were isolated together with two known compounds 24a-ethylcholesta-5, 25-dien-3P-ol (159) and sitosterol from the aerial parts of T.chamaedrys subsp. chamaedrys [82]. The plant also yielded a-amyrin and ursolic acid. The structures of the new steroidal compounds were established by NMR techniques and by comparison of similar known compounds (Table 24). 

Constit. of Centrophorus granulosus, Scymnorhinus lichiOy Etmopterus spinan and Lepidorhinus squamosus. Precursor of triterpenes and steroids in vivo. Oil. Mp -4.8 to -5.2. Bp2s 284-285 . 

Unsaturated and hydroxylated triterpenes and steroids give colored products with aromatic aldehydes in strong mineral acids, with acetic anhydride in sulfuric acid, and with inorganic salts (cerium(IV) sulfate and antimony(III) chloride, for example) in an acidic solution. These reactions have been used as the basis for determination of saponins. The analysis of Ginseng radix (Panax ginseng, Araliaceae) in Pharmacopoeia Helvetica VII, for example, relies on reaction with glacial acetic acid/sulfuric acid and spectrophotometric determination at 520 nm of the red product. The jS-aescine component of horse chestnut (Aesculus hippocastanum, Hippocastan-aceae) saponin can be determined spectrophoto-metrically after treatment with a mixture of iron(III) chloride, acetic acid, and sulfuric acid. 

Triterpenes constitute a significant portion of the lipid substances of all plants more than 4000 triterpenoids have been isolated. TTiese compounds are precursors to steroids in both plants and animals. Steroids are components of membranes in plants. Botii triterpenes and steroids occur free, as glycosides (Boar and Allen, 1973), or in other combined forms. Correct structures for many were not forthcoming until about 1940 (Connolly and Overton, 1972). The structures of triterpenes and steroids may be subdivided into about 40... 

In contrast to the previously discussed mono-, sesqui-, and diterpenes that are biosynthesized by linear condensation of five carbon units, triterpenes arise via dimerization of two famesyl pyrophosphate units to produce an intermediate compound, squalene (1) (Fig. 23.2). Squalene (usually as the 2,3-epoxide) may then be cyclized by several mechanisms from different conformations on an enzyme surface to produce the parent skeletal types of many different kinds of triterpenes that undergo subsequent modification (Banth-orpe and Chari wood, 1980 Harrison, 1985). The structures of many triterpenes and steroids may be explained by the biogenetic isoprene rule see Chapter 18) (Connolly and Hill, 1991). 

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