Cyclopropane sterols

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,... 

Another cyclopropane sterol, petrosterol (42) was isolated as the major sterol from Petrosia ficiformis and Halichondria sp. The structure was determined as... 

As the glycosides from starfish are steroidal in nature and as some known polyhydroxylated steroids with moderate cytotoxicity have been isolated from these animals, the literature since 1980 dealing with such compounds will be reviewed here. Aside from some monohydroxyste-rols from Echinaster sepositus 646), Acanthaster planci 647) - this being a source of a new cyclopropane sterol Asterias vulgaris 648), and Comasterias lurida 649), the reports deal mainly with polyhydroxylated steroids. 

Doss, G.A., Margot C., Sodano, G., and Djerassi, C. (1988) Biosynthetic studies of marine lipids. 21. Experimental demonstration of a biosynthetic interconversion of cyclopropane sterols in the sponge Calyx nicaeensis. Tetrahedron Lett., 29,6051-6054. 

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. 

The full details of the conversion of cycloeucalenol into [19- H]obtusifoliol by the microsomes of Zea mays in DjO have appeared (see Vol. 7, p. 135). The formation of a A intermediate in the enzymatic cleavage of the cyclopropane ring is excluded by the incorporation of only one deuterium atom. Both cyclo-artenol and lanosterol are converted into normal sterols by Saprolegnia ferax and Chlorella ellipsoidea. ... 

Intramolecular alkylation has been used in the synthesis of the cyclopropane side chain of the marine sterols Glaucasterol95 and Petrosterol96. During the preparation of the latter the mesylate 1 was reacted with 1.0 equivalent of potassium-tcr -butoxide in tetrahydrofuran/ben-zene at 0°C to give the trans-substituted cyclopropane 2 in >70% yield. 

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. 

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... 

Head-to-head condensation of two farnesylpyrophosphate (C]3—PP) molecules yields a G13-cyclopropane (C3)-CH intermediate which is then reduced to yield squalene H(CH2-C(CH3)=CH-CH2)3-(CH2-CH=C(CH3)CH2)3 (C30), that is, if one represents the isoprene polarities as IP and PI, one could represent squalene as (IP)3—(PI)3. Squalene is subsequently oxidized [via a squalene monooxygenase] to yield squalene 2,3-epoxide which is cyclized to the tetracyclic sterol terpene lanosterol (C30) [via squalene cyclase]. 

Heintz, R. and Benveniste, P. (1974) Enzymatic cleavage of the 9p,19-cyclopropane ring of cyclopropyl sterol in bramble tissue cultures. /. Biol. Chem., 249,4267-74. 

Israeli chemists" have synthesized some sterols having a cyclopropane system in the side chain. Some naturally occurring. sterols have recently been found to possess this... 

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)... 

The synthesis of novel 4a-substituted sterols was undertaken in the laboratory of C.H. Robinson. These compounds are potential inhibitors of sterol 4-demethylation. To prepare the desired 4-allenyl-5a-cholestan-3p-ol, the exocyclic olefin precursor was first reacted with bromoform/potassium f-butoxide to afford the geminal dibromo-substituted cyclopropane derivative. Next, methyllithium was used to bring about the rearrangement to afford the allene, and finally acidic conditions were applied for the removal of the THP protecting group. 

Treatment of the mesylate (21) with non-nucleophilic f-butoxide gives the cyclopropane (24), which serves as precursor to a marine sterol, demethylgorgosterol. 

A complex series of reactions including opening of the cyloartenol cyclopropane ring, double bond formation and isomerization, demethylation of ring carbons, and methylation of the side chain result in formation of a number of different plant sterols [24]. Sitosterol is the most common plant sterol (Fig. 7) however, plants normally contain mixtures of sterols whose proportions differ from tissue to tissue. In addition, sterol esters, sterol... 

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