Triterpene cycloartenol

Triterpenes are synthesized via the MVA pathway from two molecules of FPP that are joined by tail-to-tail condensation to squalene. Cyclization of its metabolite 2,3-oxidosqualene followed by rearrangements and methyl shifts yields various structures, mostly tetra- or penta-cyclic. 2,3-Oxidosqualene is also the precursor of plant steroids. In this case, it is cyclized to the triterpene cycloartenol, which is then converted to the compound cholesterol with the loss of three methyl groups. The oxygen of 2,3-oxidosqualene is usually retained as hydroxy group at C-3 in both triterpenes and steroids. 

Sea cucumbers (Holothuroidea, Echinodermata) appear to be unique in their mode of squalene oxide (37) cyclization. Tritium-labeled lanosterol (33), cycloartenol (32) and parkeol (38) were individually administered to the sea cucumber Holothuria arenicola. While the former two triterpenes were not metabolized [22], parkeol was efficiently transformed into 14x-methyl-5a-cho-lest-9(l l)-en-3/ -ol (39) (Scheme 3). Other A1 sterols present in H. arenicola were not found to be radioactive and were thus assumed to be of dietary origin. The intermediacy of parkeol was confirmed by the feeding of labeled mevalonate (23) and squalene (26) to the sea cucumber Stichopus californicus [15]. Both precursors were transformed into parkeol, but not lanosterol nor cycloartenol, aqd to 4,14a-dimethyl-5a-cholest-9(ll)-en-3/J-ol (40) and 14a-methyl-5a-cholest-9(ll)-en-3/ -ol. Thus, while all other eukaryotes produce either cycloartenol or lanosterol, parkeol is the intermediate between triterpenes and the 14-methyl sterols in sea cucumbers. 

Yeast does not synthesise cycloartenol or triterpenes, and so approaches to clone plant OSCs by complementation in S. cerevisiae are not feasible because of the lack of appropriate mutants. However, LS-deficient yeast mutants accumulate high levels of 2,3-oxidosqualene, favouring the synthesis of novel cycfisation products generated by heterologous expression of OSCs. The absence of lano-sterol also facilitates analysis of the reaction products. Corey and co-workers isolated a cDNA encoding Arabidopsis thaliana CS by transforming a plant cDNA expression library into such a yeast mutant and screening protein preparations derived from pools of transformants for the ability to synthesise cycloartenol by TLC [39]. 

Poralla K (1999) Cycloartenol and other triterpene cyclases. Comprehensive Natural Products Chemistry, Vol 2. Elsevier, Amsterdam, pp 299-319. 

Methylenecycloartenol (= 24-Methylcycloart-24 (24 )-en-3P-ol) (triterpene) Helianthus annuus (Asteraceae) Cycloartenol widespread CHY (-100 pM) [105]... 

Cycloartenol ferulate (triterpene ferulic ester) Cycloartenol ferulic acid key plant compound precursors HIV-1 RT (2)... 

The biosynthesis of triterpenes by photosynthetic organisms proceeds via cyclization of 2,3-oxidosqualene (92) to yield cycloartenol (93), in contrast to non-photosynthetic organisms where the cyclization product is lanosterol (94) The last step in this... 

Through a series of cyclizations, squalene oxide (C30) affords lanosterol in animals and fungi and cycloartenol in plants (Fig. 19). In both instances, the intermediate is a protosteryl cation that can also undergo a series of Wagner-Meerwein rearrangements to afford the cytotoxic cucurbitacins of melons and cucumbers. Squalene oxide in a chair-chair-chair-boat conformation yields the dammarenyl cation, a parent of numerous triterpene skeleta (e.g., lupane, oleanane, ursane, and taraxerane) contained in the saponins found in many foodstuffs, in soaps, and in several... 

Triterpenols and sterols are present as free or esterified with fatty acids (oleic acid and linoleic acid as the most relevant). Total content of triterpens is between 100-300 mg/100 g of oil. 24-Methylen-cycloartanol and cycloartenol are dominant. Erythrodiol, uvaol and triterpenic acids (ursolic, oleanolic acids etc) have been described in the imsaponifiable fraction of olive oil. The terpenoid fraction is complex and many constituents are still imdefined. 

No attempt as yet has been made to study the biogenesis of Buxus alkaloids. Indirect evidence gave rise to the presumption that in the biogenetic scheme lanosterol is followed by cycloartenol (or similar triterpene type). Goutarel (205) tentatively proposed a possible pathway via lanosterol, cycloartenol, 9j8,19-cyclo-4,4, 14a-trimethyI-5a-pregnan-3(8 - ol - 20 - one, 9, 19 - cyclo - 4,4, 14a - trimethyl - 5a - pregnan - 3,20 - dione, mono-, and diaminosteroids. 

Dimethylsterols (triterpene alcohols). The main triterpene alcohols present in olive oil are (3-amyrin, butyrospermol, cycloartenol and 24-methylene-cycloartanol (Figure 9.6). This sterol fraction is complex and many constituents are still unidentified. Itoh and his co-workers (1981) used argentation thin layer chromatography and GC-MS to identify minor 4,4-dimethylsterols present in olive oil and olive pomace oil ((3-residue oil). 

Dimethyl sterols (triterpene alcohols) Sample (j-Amyrin A8-Sterol a- Amyrin Cycloartenol A7-Sterol 24-Methylene cycloartanol Others... 

The lanostanes are the most relevant group of the tetracyclic triterpenes (Tables 12-13). Many of this type of compounds are described as antiinflammatories and their mechanism of action has been studied frequently. Cycloartenol and some 3,4-seco-lanostane derivatives have been reported to have activity also. 

Ehrhardt, J.D., L. Hirth, and G. Ourisson Etude des tri-terpenes tetracycliques des feuiUes de tabac. Presence de cycloartenol absence de lanosterol [Study of the tetracyclic triterpenes in tobacco leaf. Presence of cycloartenol absence of lanosterol] Compt. Rendu Acad. Sci. 260 (1965) 5931-5934. 

Two molecules of famesyl pyrophosphate are joined head-to-head to form squalene, a triterpene, in the first dedicated step towards sterol biosynthesis (Fig. 8.4). Squalene is then converted to 2,3-oxidosqualene, which next can be cyclized to the 30 carbon, 4-ring structure cycloartenol by the enzyme cycloartenol synthase (EC 5.4.99.8). Cycloartenol can be further modified by reactions such as desaturation or demethylation to form the common sterol backbones such as... 

The sterols (0.6%) are mainly )8-sitosterol, camp-esterol and stigmasterol. The triterpenes (0.04%) include cycloartenol, cycloartanol, 24-methylene-cycloartenol and probably a-amyrin (Fedeli et aL, 1966). 

When squalene 2,3-epoxide (2) is cyclized via a chair-boat-chair-boat sequence, the first isolable cyclic intermediate (in plants) is cycloartenol (3) (Fig. 23.6). Cycloartenol proves to be a key intermediate in the synthesis of certain other triterpenes and plant sterols. Many steroids are common [if not ubiquitous, e.g., -sitosterol (4), stigmas-terol (5), and campesterol (6) (Fig. 23.6)] and it is probable that these pathways exist in all plants (Goad and Goodwin, 1973 Grunwald, 1975 1980). Cholesterol (7) occurs in small quantities, but appears to be a universal constituent of plants. This sterol serves as a key intermediate in the synthesis of a number of other steroidal compounds. A new system of numbering sterols was recommended in 1989 (Goad, 1991a). 

Seedlings of cucumber, Cucumis sativus, converted the triterpene (51) into cucurbitacin C (52) microsomal fractions from seedlings of Cucurbita maxima converted squalene 2,3-epoxide into 10a-cucurbita-5,24-dien-33-ol. Neither parkeol (53) (Fig. 23.1), cycloartenol (3), 11-ketocycloartenol, or 24,25-dihydro-9a,lla-epoxyparkeol were incorporated significantly, and no products with a cu-curbitane skeleton were isolated (Balliano et al., 1983 Harrison, 1985). 

The sweet-tasting compounds from Abrus fruticulosus and A. precatorius (Fabaceae) also are a mixture of triterpene glycosides related to cycloartenol (Choi et al., 1989 Fullas et al., 1990). Abrusosides A-D (19-22) are 30-100 times sweeter than a 2% solution of sucrose. 

Squalene can be converted to numerous families of triterpenes characterized by the different conformations it takes on the surface of the cyclizing enzyme. Apart from lanosterol (1-A) and cycloartenol (2-A), which are the precursors of sterols in different organisms, one can cite /3-amyrin (III) and serratene (IV) as typical examples. In this chapter we are concerned only... 

---