Cycloartenol

The path from squalene (114) to the corresponding oxide and thence to lanosterol [79-63-0] (126), C qH qO, cholesterol [57-88-5] (127), and cycloartenol [469-38-5] (128) (Fig. 6) has been demonstrated in nonphotosynthetic organisms. It has not yet been demonstrated that there is an obligatory path paralleling the one known for generation of plant sterols despite the obvious stmctural relationships of, for example, cycloartenol (128), C qH qO, to cyclobuxine-D (129), C25H42N2O. The latter, obtained from the leaves of Buxus sempervirens E., has apparentiy found use medicinally for many disorders, from skin and venereal diseases to treatment of malaria and tuberculosis. In addition to cyclobuxine-D [2241-90-9] (129) from the Buxaceae, steroidal alkaloids are also found in the Solanaceae, Apocynaceae, and LiUaceae. 

Several other naturally occurring antioxidants have been identified in oils. Sesamol [533-31-3] (6) occurs as sesamoline [526-07-8], a glycoside, in sesame seed oil. FemUc acid [1135-24-6] (7) is found esterified to cycloartenol [469-38-5] in rice bran oil and to 3-sitosterol in com oil. Although it does not occur in oils, rosemary extract has also been found to contain powerful phenoHc antioxidants (12). 

Knob (southern Canterbury Administrative Region see Fig. 2.11) and cycloartenol methyl ether [58] was found in plants from Clarke River, whereas four other collections failed to yield any TMEs. Similarly, populations of C. rigida (Raoul) Zotov from eastern South Island do not synthesize TMEs, whereas those from western South Island were shown to accumulate p-amyrin methyl ether [59]. An additional difference between populations from these two sites lies in the capacity of the former to produce short-chain wax components, as opposed to long-chain compounds from the latter (Cowlishaw et al., 1983). Different chemodemes were also described for C. cheesemanii (Hackel ex Cheesem.) Zotov plants from North Island exhibited lupeol methyl ether as the dominant compound along with lesser amounts of arun-doin and two unidentified compounds, whereas populations from the South Island had arundoin as the major compound with lesser amounts of lupeol methyl ether. 

Phytosterols have been demonstrated as being anti-cancer components in the diet (Awad and Fink 2000). Scientific studies indicate that phytosterols may offer profection against colon, breast and prostate cancers (Vanderhaeghe and Bouic, 2000). The possible mechanisms, as reported by these authors, include the effect of phytosterols on membrane structure and function and on the signal transduction pathways that regulate tumor growth and apoptosis. The rice bran derived phytosterol-cycloartenol-ferulic acid ester on the central nervous system has been studied by Hiraga et al. (1993). 

HIRAGA Y, NAKATA N, JIN H, ITO S, SATO R, YOSHIDA A, MORI T, OZEKI M, IKEDA Y (1993) Effect of the rice bran-derived ph)itosterol cycloartenol ferulic acid ester on the central nervous system. Arzneimittel-Forschung, 43(7) 715-21. 

As described earlier, the dichotomy at the point of squalene (26) cyclization has been used as a distinguishing feature of photosynthetic and non-photosynthetic organisms [1], Cycloartenol (32) is the primary cyclization product in the former group, while in the latter, lanosterol (33) is initially produced (Scheme 2). Recent investigations into the cyclization of squalene in marine organisms have provided interesting results. 

Until recently, the only marine example of cycloartenol (32) production was in the chrysophyte Ochromonas sp. [20], A survey, documenting the products of squalene oxide (37) cyclization (see Scheme 3) using crude enzyme preparations of various algal phyla has recently been reported [21]. Interestingly, while all... 

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. 

Triterpenoid saponins are synthesized via the isoprenoid pathway.4 The first committed step in triterpenoid saponin biosynthesis involves the cyclization of 2,3-oxidosqualene to one of a number of different potential products (Fig. 5.1).4,8 Most plant triterpenoid saponins are derived from oleanane or dammarane skeletons although lupanes are also common 4 This cyclization event forms a branchpoint with the sterol biosynthetic pathway in which 2,3-oxidosqualene is cyclized to cycloartenol in plants, or to lanosterol in animals and fungi. 

Fig. 5.1 Cyclization of 2,3-oxidosqualene to sterols and triterpenoids. The 2,3-oxidosqualene cyclase enzymes that catalyse the formation of the different products are indicated LS, lanosterol synthase CS, cycloartenol synthase LuS, lupeol synthase PAS, P-amyrin synthase aAS, a-amyrin synthase.

Expressed sequence tag (EST) analysis of cDNAs from specific plant tissues has proved to be a valuable tool for the identification of genes for secondary metabolite biosynthesis.36 We have used this approach to identify two distinct sequences predicted to encode OSCs from cDNA libraries from roots of diploid oat (Avena strigosa).35 One of these sequences is highly homologous to cycloartenol... 

The deduced amino acid sequence of AsbASl contains the conserved DCTAE motif implicated in substrate binding in OSCs,37 and also four conserved QW motifs that are characteristic for the OSC superfamily.38 Remarkably, AsbASl is clearly distinct from the other cloned PAS enzymes that have been characterized to date from other plant species, and is more closely related to lanosterol synthases from animals and fungi than to triterpenoid synthases or cycloartenol synthases from plants (Fig. 5.3).35 There are substantial mechanistic differences in the processes of... 

Genetic analysis indicates that two of the 10 sad mutants of A. strigosa that we isolated represent different mutant alleles at the Sadi locus.6 These mutants accumulate radiolabelled 2,3-oxidosqualene but not p-amyrin when the roots are fed with 14C-labelled precursor mevalonic acid, suggesting that the triterpenoid pathway is blocked between 2,3-oxidosqualene and P-amyrin.34 The roots of these mutants also lack detectable P-amyrin synthase activity, but, like the wild type and the other mutants, are unimpaired in cycloartenol synthase (CS) activity and sterol biosynthesis.34 The transcript levels for AsbASl are substantially reduced in roots of sadl mutants, while AsCSl transcript levels are unaffected,35 suggesting that the sadl mutants are either mutated in the AsbASl gene itself or in a gene involved in its regulation. 

HENRY, M., RAHIER, A., TATON, M., Effect of gypsogenin 3,0-glucuronide pretreatment of Gypsophila paniculata and Saponaria officinalis cell suspension cultures on the activities of microsomal 2,3-oxidosqualene cycloartenol and amyrin cyclases, Phytochemistry, 1992,31,3855-3859. 

TATON, M., BENVENISTE, P., RAHIER, A., N-[(l,5,9)-tnmethyl-decyl]-4a,10-dimethyl-8-aza-trans-decal-3P-ol A novel potent inhibitor of 2,3-oxidosqualene cycloartenol and lanosterol cyclases, Biochem. Biophys. Res. Comm., 1986, 138, 764-770. 

FANG, T-Y., BAISTED, D.J., 2,3-Oxidosqualene cyclase and cycloartenol-S-adenosylmethionine methyltransferase activitites in vivo in the cotyledon and axis tissues of germinating pea seeds, Biochem. J., 1975,150, 323-328. 

Sitosterol Campesterol Stigmasterol Unusual sterols Cycloartenol Cholesterol, minute quantities... 

Buxus alkaloids have a imique steroid-triterpenoid pregnane type skeleton with C-4 methyls, 9fl, lOp cycloartenol system with a degraded C-20 side chain [21-33]. These alkaloids exhibit varions biological activities including anti-HIV, anti-TB,... 

Liang Y et al (2009) Antisense suppression of cycloartenol synthase results in elevated ginsenoside levels in Panax ginseng hairy roots. Plant Mol Biol Rep 27 298 Lawrence GHM (1951) Taxonomy of vascular plants. Macmillan Press, New York, NY Fountain MS (1986) Vegetation associated with natural populations of ginseng Panax quinquefolium in Arkansas USA. Castanea 51 42... 

Wood SG, Gottheb D (1978) Evidence from mycelial studies for differences in the sterol biosynthetic pathway of Rhizoctonia solani and Phytophthora cinnamomi. Biochem J 170 343 Nes WD et al (1986) A comparison of cycloartenol and lanosterol biosynthesis and metabolism by the Oomycetes. Expeiientia 42 556... 

Among the recent outstanding contributions to the chemistry of natural products is the conformational analysis designed by Derek Barton. He used it for the structural determinations of many complex molecules such as P-amyrin and cycloartenol. Robert B. Woodward was involved in the structural determinations of penicillin, strychnine, patalin, terramycin, aureomycin and the synthesis ofVitamin B12. 

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