Formation of cycloartenol

In animals (Chapter 1) squalene 2,3-oxide is first converted into lanosterol (TA) and this reaction also occurs in yeasts. However, in higher plants and algae the first cyclic product is cycloartenol (2-A). 

In order to save space and repetition of structural fomudae sterol structures are designated by a number (nucleus) and a letter (side chain). The keys are given in Figs. 1 and 2. 

The enzyme involved is squalene 2,3-oxide cycloartenol cyclase and the substrate is the S enantiomer. The reaction is initiated by H attack on the oxygen of the epoxy group of the substrate held in the chair, boat, chair, boat unfolded conforma- 

The presence of only 4 deuteriums in poriferasterol (4-B) formed from [C HjJmethionine in Ochromonas implies the formation of an intermediate ethyl-idene compound. Feeding experiments showed that the 28-Z isomers ethylidene lophenol (5-C) and isofucosterol (4-C) are both effectively incorporated into 

A similar mechanism for the formation of alkyl sterols functions in Euglena and the Xanthophyte Monodus subterraneus. 

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Kg. 2. Proposed mechanism for formation of cycloartenol from squalene 2,3-oxide (Rees et al 1968). 

A reaction unique to plant sterols is the opening of the cyclopropane ring generated in the formation of cycloartenol. However as already mentioned, smother reaction specific to plants is alkylation at C-24. As the enzyme which opens the cyclopropane ring in general acts only on alkylated derivatives, it is logical to discuss the alkylation reactions first. However, an enzyme preparation will occasionally act on nonalkylated intermediates, as in the case just discussed in which an Euphorh/u latex isomerizes cycloartenol to lanosterol. 

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.

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 formation of cyclosteroids through intramolecular substitution of a sulphonate by a carbanion, used successfully in the preparation of 5a,7a-cyclosteroids, has provided a route to a variety of curious cyclic structures. The 9jS,i9-cyclo structure (13) found in cycloartenol was obtained [yi] when... 

As expected, lanosterol (70) but not cycloartenol (72) was converted in rats into cholesterol on the other hand both triterpenoids are utilized by Zea mays in the formation of C-24-alkylated sterols. Sterol formation has been demonstrated in the fern Polypodium vulgare, tobacco, and Calendula... 

The syntheses of labelled lanosterol, cycloartenol, and parkeol derivatives for use in biosynthetic studies have been described. Terminal labelling of the side-chain [25- C] or [26,27- H6] was achieved by the formation of Wittig intermediates with the trisnortriterpenoid units followed by reaction with labelled acetone. Methods for the removal of one or both methyl groups from 4,4-dimethyl-steroids have been published. Lanosterol has been degraded to the trimethyl-pregnenolone (54). 

The present state of knowledge of terpenoid biosynthesis does not allow many detailed conclusions to be reached on its taxonomic importance. However, some gross differences at the phyla level are apparent. This review has already commented on differences observed in the formation of steroidal A - and A -double bonds, 24-alkyl groups, and whether lanosterol or cycloartenol is formed from squalene epoxide. 

Fig. 7. The formation of 24-methylene cycloartanol, cyclolaudenol and cyclosadol by methylation of cycloartenol.

Fig. 10. Retention of configuration on formation of the cyclopropane ring of cycloartenol.

The scheme for steroid biosynthesis is the same in both plants and animals up to the formation of the carbocation 3-2. The biosynthesis diverges at this point in animals the methyl group at Cg migrates to afford lanosterol (4-1) as an isolable product (Scheme 2.4). The first steroidal product that can be isolated in plants, cycloartenol (4-2), features a cyclopropyl ring fused on to ring B at carbons 9,10. 

More direct methods for the degradation of the side-chain of cyclolaudenol have been published/ It has been shown, using the squalene 2,3-oxide (38) with a chiral methyl group, that the 1,3-proton loss in the formation of the cyclopropane ring of cycloartenol occurs with retention of configuration at the C-10 methyl group/ ... 

One of the clear distinctions between higher animals and plants is in the products resulting from cyclization of squalene epoxide (76). Plants form cycloartenol (78) whereas animals form lanosterol (80). Moreover, animals are unable to metabolize cycloartenol. Further examples of cycloartenol formation are reported with a tissue culture of Rubus fructicosus and Pinus pineaf Cycloartenol and 24-methylenecycloartanol are recovered unchanged with microsomes from the Rubus tissue culture but cycloeucalenol (79) is metabolized... 

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