Polycyclic triterpene

The isoprenoids contribute most to the list of structural similarities in the sea and on land. They range from common classes in both ecosystems, such as drimane sesquiterpenes, to rare classes in the sea, such as the trichothecenes (Chart 8.3.11). The similarity in marine and terrestrial polyether triterpenes (Chart 8.3.12) may be seen as convergence toward chemically favored structures, starting from squalene as a biosynthetic precursor. Similar conclusions may apply to polycyclic triterpenes. 

Double Sharpless epoxidation was also applied to the synthesis of a key intermediate 10 to the meso-compound 11 that is related to teurilene, abioactive polycyclic triterpene isolated from red alga Laurencia obtusa,4 The reaction of ( , )-Bisallylic alcohol 9 gave the bisglycidic alcohol 10 with 80% de and 89% ee for each epoxidation (Scheme 6AA.4). 

Cyclization of squalene is via the intermediate squalene-2,3-oxide (Figure 5.55), produced in a reaction catalysed by a flavoprotein requiring O2 and NADPH cofactors. If squalene oxide is suitably positioned and folded on the enzyme surface, the polycyclic triterpene structures formed can be rationalized in terms of a series of cycliza-tions, followed by a sequence of concerted Wag-ner-Meerwein migrations of methyls and hydrides... 

Wendt KU, Schultz GE, Corey EJ and Liu DR (2000) Enzyme mechanisms for polycyclic triterpene formation. Angew Chem Int Edn 39, 2812-2833. 

Protonated 2,3-epoxysqualene is the biosynthetic precursor of polycyclic triterpenes such as protostanes and dammaranes. The geneses of the cations of proto-stane and dammarane start from two different conformers of the carbenium ion, which arise intermediately from opening of the protonated 2,3-epoxysqualene. 

Outline. Saponins, sometimes termed saponosides, are glycosidic derivatives of steroids or polycyclic triterpenes which - dissolved in water - behave like soaps (lat. sapo ), i.e., produce a stable foam, emulsify fatty oils, and stabilize suspensions. They are able to lower the surface tension of aqueous solutions and to cause haemolysis. This is due to their lyobipolar character which is based on the lipophilic aglycone and the highly hydrophilic carbohydrate moiety. There is only one report on triterpenoid saponins in the Solanaceae (Cestrum parqui L Herit., see Sect. 7.5.1.), whereas steroidal saponins are common metabolites of this family. Saponins do not occur in the Convolvulaceae. 

Squalene is the precursor of sterols and polycyclic triterpenes. In the 1950s, G. Stork (Columbia University) and A. Eschenmoser (ETH, Zurich) proposed that the biogenetic conversion of squalene to lanosterol involved a synchronous oxidative cyclization pathway. The transformation is acid catalyzed and proceeds through a series of carbonium ions to allow the closure of all four rings. There is now ample evidence that the first step is the selective epoxidation of the -double bond to form 2,3-oxidosqualene (Fig. 5.21). 

Squalene 2,3-oxide has been proposed to account for a vast array of polycyclic triterpenes in natureJ The synthesis of 6-amyrin by van Tamelen and his associates mimics the biological cyclization process, featuring the stereoselective generation of five asymmetric centres during a polyolefinic cyclization of the terminal epoxide Preparation of DIE Component ... 

Saponins are a widespread class of bioactive compounds produced by many plant species. Saponins consist of a hydrophobic polycyclic triterpenes C-30 or steroidal C-27 sapogenin (aglycone/genin) and one or two (rarely three) hydrophilic glycoside moieties attached to backbone. Because of their amphiphilic properties, saponins are amphiphihc glycoconjugates which are able to interact with cell membranes and are also able to decrease the surface tension of an aqueous solution. This activity is the reason for the name saponin, derived from the Latin word sapo, which refers to the formation of a stable soap-like foam in aqueous solution [1,2]. 

The method applied consists in a prior, basic hydrolysis (saponification) of the oil sample, followed by thin layer chromatography (TLC) fractionation of the classes of compounds, namely hydrocarbons, tocopherols, long-chain aliphatic alcohols, triterpenic alcohols, methyl sterols, sterols and triterpenic dialcohols. This procedure loses all information about the combination of polycyclic triter-penes with fatty acids. 

With nearly 20 years of experience on plant-derived natural products, NPRL has identified numerous active anti-HIV compounds including polycyclic diones, saponins, alkaloids, triterpenes, polyphenols, flavonoids and coumarins. Triterpenes have diverse structures and pharmacological activities. 

An impressive cationic domino polycyclization has been developed by Corey and coworkers in their short and efficient enantioselective total synthesis of aegicer-adienol (1-150), a naturally occurring pentacyclic nor-triterpene belonging to the 3-amyrin family [42]. Thus, the treatment of the enantiopure monocyclic epoxy tet-raene 1-147 with catalytic amounts of methylaluminum dichloride induces a ca-tion-JT-tricyclation by initial opening of the epoxide to form the tetracyclic ketone 1-148 in 52 % yield, and its C-14 epimer 1-149 in 23 % yield, after silylation and chromatographic separation (Scheme 1.37). Further transformations led to aegicer-adienol (1-150) and its epimer 1-151. 

Scheme 3. Cationic domino polycyclization to the triterpene dammarenediol II...

Only few sponges are also known to produce triterpenes, such as squalene-derived cyclic ethers consisting of two separate polycyclic systems connected with different types of linkers. The first is sipholenol (118), isolated from the Red Sea sponge Siphonochalina siphonellaP Structurally related sodwanones F (119), yardenone... 

Studies on the ABC -I- E ring construction (189) of the pentacyclic triterpene skeleton were recently described by ApSimon et al. The route has the advantage of rapid provision of a polycyclic species with preformed stereochemistry, countered by the disadvantage of uncontrolled stereochemistry in the cyclization step. 

The meaning of 5a is that the hydrogen atom in position 5 lies below the general plane of the rings. All substituents which lie below this plane in other positions are designated a, and those that lie above this plane are called jS. The a-substituents are represented by dotted lines, and the jS-substituents by thick lines. These symbols, a- and )3-, are used, with similar meaning, for other polycyclic structures, also, such as triterpenes and alkaloids. The complexity of such structures makes the application of (/ ) and (5) nomenclature too difficult. 

The triterpenes encompass several families of polycyclic isoprenoids. The parent C30 carbon chain is derived from the head-to-head condensation of two molecules of FPP to form squalene (7). The reaction parallels those involved in the formation of chrys-anthemyl pyrophosphate and phytoene (vide supra) and proceeds, as they do, via a cyclopropane intermediate, presqualene pyrophosphate (95) a series of Wagner-Meerwein rearrangements are involved before the final product is released (Figure 3.31) (Blagg etal. 2002). 

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