X-Ray Crystallography and the Chemistry of the Steroids. Part I
Abstract
A survey has been made of the X-ray crystallography of some eighty sterol derivatives belonging mainly to the cholesterol and ergosterol series but including also calciferol and other photoderivatives of ergosterol and some higher plant and animal sterols. The measurements are recorded in four tables and include determinations of unit cell size, space group and some data on the crystal morphology and optics. In three cases, cholesteryl chloride, bromide and cholesteryl chloride hydrochloride, Patterson projections have also been derived from the intensities of the X-ray reflexions of the h0l planes. These confirm earlier deductions on the shape and size of the sterol molecules, proving that these are roughly lath-shaped, 20 × 7 × 4 A, and the details of the patterns can also to some degree be correlated with the actual arrangement of the carbon atoms in the sterol ring system and with the positions of the chlorine and bromine atoms. The arrangement of the molecules in the crystal units is closely that given by the preliminary examination from the optic orientation, and this has therefore been employed to suggest in each of the remaining sterol crystal structures the probable molecular arrangement. Among the eighty compounds studied a number of different types of crystal structure appear. An attempt is made to group these in a general geometric classification depending upon the relative orientation of the molecular axes, thickness, width, and length to the crystallographic axes a, b, and c. In monoclinic crystals three main groups are distinguished in which the monoclinic b axis is the direction of the molecular thickness, width or length, and the orthorhombic and triclinic crystals are classified by comparison with the monoclinic varieties. Inside each group divisions are based first on the multiplicities, the numbers of molecules present, and secondly on the space groups. Altogether 105 different sterol structures are included in the classification, and of these seventy-seven fall into the second of the three main groups described above, which includes cholesteryl chloride and bromide and has been called the normal type of sterol structure. oThe crystallographic measurements as a whole are discussed in their bearing on specific chemical problems under the following headings: (a) Characterization and identification The X-ray data have been applied particularly among the higher plant and animal sterols both to identify individual constituents (e.g. stigmasterol in phytosterol mixtures), to distinguish additional crystal forms (e.g. two types of cerevisterol) and to characterize new sterols and relate these to previously known compounds (e.g. a sterol from rubber). (b) Molecular weight determinations Molecular weight measurements have been carried out on cholestenone, ergotetraene, γ -spinastenol acetate, ergosterol H2O, stigmasterol H2O, γ -sitosterol H2O and β sitosterol from rubber. In the case of crystals of cholestanol, β -ergostadienetriol and Δ -4-cholestene-7-ol, the measurements are used to estimate water of crystallization. (c) The stereochemistry of the carbon skeleton The X-ray measurements indicate that the general configuration of the sterol ring system must be flat, but so far it has been impossible to correlate stereochemical changes at particular ring junctions with crystallographic changes, e.g. between rings C and D (α -ergostenol, β -ergostenol), B and C (lumisterol), and A and B (coprostane, cholestane). (d) The effect of substituents on the crystallography of the sterols (i) The position of the hydroxyl group. A hydroxyl group at C3 of the sterol skeleton generally, but not invariably, leads to double-layer formation in the crystal structure and vice versa, a double-layer crystal structure usually indicates the presence of a terminal hydroxyl group. Exceptions are cholestane 6-ol which shows a double layer, and pyrocalciferol which does not. Brassicasterol, cerevisterol, and the spinasterols all probably have hydroxyl groups at C3. The position of i-cholesterol (which shows no double layer) is obscure. (ii) The slereochemistry of the hydroxyl group at C3. It is not possible to distinguish at this stage between the two possible configurations of the hydroxyl group at C3. In cholesteryl chloride and bromide, the chlorine and bromine atoms must lie closely in the plane of the ring system. α -Chlor-cholestane is correlated crystallographically with cholesteryl chloride. (iii) The position of the double bonds. The introduction of either hydroxyl groups or halogens at the double-bond system usually produces radical changes in the crystallography which makes simple comparison difficult. The Patterson analysis of cholesteryl chloride hydrochloride provides, however, definite evidence that the extra chlorine atom is at C5. The crystallography of both the hydroxyl and maleic anhydride derivatives of ergosterol is in agreement with their present chemical formulae but provides no certain proof of the correctness of these. (e) A comparison of the crystallography of different sterols-monohydroxy compounds There is a group of sterols, including ergosterol and many of the higher plant and animal sterols, which show particularly close resemblances in crystal structure to one another. While inclusion in this group must indicate close similarity both in sterol skeleton and molecular arrangement, deviations do not necessarily seem to have a chemical significance. (f) The structure of calciferol Calciferol, while showing certain differences from the characteristic sterol group mentioned above, also shows similarities, particularly in c-plane intensities. It seems unlikely therefore that the actual distribution of the atoms in the molecule differs considerably from that in ergosterol. Conclusion Many of the outstanding problems of the chemical structure of the sterols can only be settled by exact analysis. The present survey has indicated a number of compounds that are suitable for such treatment.
- Publication:
-
Philosophical Transactions of the Royal Society of London Series A
- Pub Date:
- December 1940
- DOI:
- 10.1098/rsta.1940.0010
- Bibcode:
- 1940RSPTA.239..135B