Rotational isomerism about the 17(20)-bond of steroids and euphoids as shown by the crystal structures of euphol and tirucallol.

Abstract

The influence of configuration at C-20 on rotation about the 17(20)-bond in steroids and euphoids was examined by x-ray crystallographic studies of the C-20 epimers euphol and tirucallol. The H atom on C-20 was in back next to C-18 in the crystal structures of both of the compounds, and C-22 was found to be cis-oriented ("left-handed") to C-13 in euphol and trans-oriented to it ("right-handed") in tirucallol.The results, which are consistent with the known left-handed crystal structure of 24(25)-dihydroeuphol and right-handed crystal structure of cholesterol and other natural sterols, lend further credence to the earlier suggestion that rotational isomerism at the 17(20)-bond can arise in C-20 epinters and that there is preference for an arrangement with the 20-H atom adjacent to C-18.It is known from x-ray data (1-3) that in the crystalline state, sterols with the natural configuration (20a-H atom, usually 20R in the sequence rule) have a conformation about the 17(20)-bond such that, in the usual view of the molecule, C-22 is to the right. As we suggested earlier (4, 5), the preference for this "right-handed" rotational isomer probably derives from its having the smallest of the groups on C-20 (the H atom) in front and, therefore, adjacent to C-18 in a pseudo-1,3-diaxial fashion. If this were the correct explanation, the H atom on C-20 should remain adjacent to C-18 after inversion. This would place C-22 on the left ("left-handed" isomer)We undertook a study of this stereochemistry, because the ability of the sterol side chain to assume a right-handed conformation without having a methyl group in front seems to be of biological importance. There is a clear correlation between the biological activities of (20R)-sterols (which can have this stereochemistry) and (E)-17(20)-dehydrocholesterol with C-22 fixed to the right (5)(6)(7)(8)(9)(10)(11). Similarly, the activities of (20S)-sterols correlate with (Z)-17(20)-dehydrocholesterol (5-10). If only one of the 17(20)-dehydrosterols is active, it is the right-handed (E)-isomer, and then of the C-20 epimers only the one with the (20R)-configuration is active (5-10). These correlations have been found in the ability of sterols to perform what is thought to be the bulk membrane function in yeast (5, 6), to be metabolized by a protozoan (7,8), and to induce formation of oospores in an oomycete (9, 10). If, on the other hand, both of the 17(20)-dehydrosterols are active, as they are in depressing hepatic cholesterol synthesis after being fed to mice (11), then both of the C-20 epimers of cholesterol are active (11).To determine whether inversion of the C-20 configuration of sterols is actually accompanied in the solid state by transfer of C-22 from the right to the left side of the molecule, we have tried to grow large enough crystals of 20-epicholesterol, prepared as described (12), to permit x-ray analysis.Unfortunately, crystals of adequate size have not been obtained, so we turned our attention to the naturally occurring (13) C-20 epirners euphol and tirucallol...

Euphane triterpenoids of Cassipourea lanceolata from the Madagascar rainforest

“…This argument was derived from careful analysis of the ROESY spectra of the two diastereomers, kansenone [C-20 ( R )] and epi-kansenone [C-20 ( S )] and by comparison with previously reported compounds. The configurations determined for the five compounds discussed in the literature, namely kansenone, epi-kansenone, kansenonol, 11-oxokansenonol and kansenol, were consistent with X-ray crystallographic studies of euphane and tirucallane triterpenoids (Nes et al, 1984; Wang et al, 2003). In the ROESY spectra of 1 , correlations of H 3 -21 to H 2 -16, H-17, and H 2 -23, those of H 3 -18 to H-16α (δ H 1.34, m) and H-20, and that of H-22a (δ H 1.70, m ) to H-12b (δ H 1.58, m ) were observed in addition to the absence of correlations between H 3 -21 and H 3 -18 and between H 3 -21 and H 2 -12 (Fig.…”

Isohelianol: A 3,4-seco-Triterpene Alcohol from Sasanqua Oil

“…The conformer of simulated 3 shows C-22 of the side chain at C-17 oriented into a "left-handed" conformation (C-22 cis-oriented to C-13) similar to that of 5 7,12 and to the crystal structure of 7. 15 This was consistent with the NOE experiment done in solution, thus confirming the proposed structure of 3. On alkaline hydrolysis, acetate 3 yielded the free alcohol, 3,4-seco-19(10f9)-abeo-8R,9 ,10R-eupha-4,24-dien-3-ol (1).…”

“…and the crystal structures of 815 and euferol [19(10f9)-abeo-8R,9 ,10R-tirucalla-5,24-dien-3 -ol] acetate 16. This conformation of 4 was consistent with results from the NOE experiments carried out in solution and supported the proposed structure as depicted in 4.The NOE correlation of H-21 is an essential aid for assignment of stereochemistry at C-20, i.e., for the discrimination of euphane (20R)/tirucallane (20S) and 3,4-seco-migrated euphane/tirucallane triterpenes.…”

Triterpenoid levels are reduced during Euphorbia tirucalli L. callus formation

“…This is the first report to list the major m/z signals of these eleven compounds, which were extracted and analyzed by GC-MS at the same time. The identification of these peaks should be performed with reference to the previously reported Euphorbia compounds with a molecular weight of 426: euphol (Hashimoto 2001;Nes et al 1984), tirucallol (Nes et al 1984), glut-5-en-3-b-ol (Khan et al 1987), cycloeuphordenol (Khan et al 1988), euphorginol (Rasool et al 1989), a-amyrin (Malik et al 1980), lanosterol (Nemethy and Calvin 1983). Functional analyses of the synthases of triterpenoids that accumulate in the laticifers of E. tirucalli plants should also be performed, as has been done in plants that do not possess laticifers (Sawai et al 2006;Suzuki et al 2006;Ohyama et al 2009).…”