Cyclopropane sterols biosynthesis

Cyclopropane ring openings have been proposed to account for the biosynthesis of several unconventional sterols. Ficisterol (106) [70, 71] is of the 26-norergostane type and contains the rare 23-ethyl substituent. Its biosynthesis became apparent following the isolation of the trace cyclopropane sterol,... 

In green plants, which contain little or no cholesterol, cydoartenol is the key intermediate in sterol biosynthesis.161-1623 As indicated in Fig. 22-6, step c, cydoartenol can be formed if the proton at C-9 is shifted (as a hydride ion) to displace the methyl group from C-8. A proton is lost from the adjacent methyl group to close the cyclopropane ring. There are still other ways in which squalene is cyclized,162/163/1633 including some that incorporate nitrogen atoms and form alkaloids.1631 One pathway leads to the hop-anoids. These triterpene derivatives function in bacterial membranes, probably much as cholesterol does in our membranes. The three-dimensional structure of a bacterial hopene synthase is known.164 1643 Like glucoamylase (Fig. 2-29) and farnesyl transferase, the enzyme has an (a,a)6-barrel structure in one domain and a somewhat similar barrel in a second domain. 

Fig. 13. Opening of the 19-cyclopropane ring during sterol biosynthesis in photosynthetic organisms. This is catalysed by a microsomal enzyme that appears to require no cofactors and generates a sterol product that possesses a lOp-methyl group and a A -double bond.

More than twenty sterols with cyclopropanes or cyclopropenes have been isolated from marine organisms [53], The majority of these come from sponges, although significant numbers have been isolated from dinoflagellates and co-elenterates. There are no terrestrial organisms known to contain such sterols and thus their biosynthesis is purely a marine problem. 

Cycloartenol (94) rather than lanosterol is thought to be the crucial triterpenoid intermediate in the biosynthesis of plant sterols, although in a chlorophyll-containing phylum there appears to be no direct correlation between ability to photosynthesize and the operation of the cycloartenol pathway.163 The cleavage of the cyclopropane ring of (94) between C-9 and C-19 should be accompanied by the incorporation of a proton at C-19, possibly from the medium. That this is the case in pea was shown164 by the incorporation of deuterium specifically at C-19 of cycloartenol obtained from... 

Other biogenetically distinct cyclopropane side chain substitution patterns are typified by the sponge sterols calysterol (25) isolated from Calyx nicaensis, and petrosterol (19) found in Petrosia. Unlike the biosynthesis of gorgosterol-type (17)... 

Using trideuterated methionine on methyl (Met-ds), Djerassi s group showed that the biosynthesis of 24(E)-propylidene cholesterol did not utilize cyclopropanic intermediates, but more probably 24-vinylcholesterol a sterol that has not yet been identified in a living organism. The stages of this biosynthesis are summarized in Figiue 10.1 (Kokke et al, 1984). 

Djerassi, C. and Doss, G.A. (1990) Structure and biosynthesis of cyclopropane-containing sterols of marine origin. New J. Chem., 14, 713-719. 

Doss, G.A., Proudfoot, J.R., Silva, C.J., and Djerassi, C. (1990) Biosynthetic studies of marine lipids. 24. Experimental demonstration of an unprecedented cyclopropane-cydopropene rearrangement in the biosynthesis of the sponge sterol petrosterol. f Am. Chem. Soc., 112, 305-310. 

Silva, C.J. and Djerassi, C. (1991) Sterols in marine invertebrates. Part 64. Isolation, stereochemistry, and biosynthesis of sormosterol, a novel cyclopropane-containing sponge sterol. Collect. Czech. Chem. Commun., 56, 1093-1105. 

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