Steroidal compounds not occurring

Fig. 7.2 Chemical structures of commonly used steroidal compounds not occurring naturally.

P-Hydroxy steroids which contain the 5,7-diene system and can be activated with uv light to produce vitamin D compounds are called provitamins. The two most important provitamins are ergosterol (1) and 7-dehydrocholesterol (3). They are produced in plants and animals, respectively, and 7-dehydrocholesterol is produced synthetically on a commercial scale. Small amounts of hydroxylated detivatives of the provitamins have been synthesized in efforts to prepare the metaboHtes of vitamin D, but these products do not occur naturally. The provitamins do not possess physiological activities, with the exception that provitamin D is found in the skin of animals and acts as a precursor to vitamin D, and synthetic dihydroxalated... 

The mechanism of reaction with steroids has not been elucidated. Various nonquantitative reactions occur simultaneously. Cyclopentenyl cations have been postulated as intermediates which condense with anisaldehyde to yield colored compounds [4]. It is probable that triphenylmethane dyes are also formed with aromatic compounds. 

Contrary to this bicyclic series, the equilibration of the a- and the b-cyano isomers derived from the steroid enones 92 (R=H or CH3) does not occur. It has also been impossible to produce the B-cyano isomer from the hydrocyanation reaction. This result was explained by the fact that in the steroid series, there is a strong steric interaction between the cyano group and the C-ll methylene group of ring C in the boat-like conformation 95 (cf 98). Consequently, addition to the B-face never occurs in these compounds. This was confirmed by the fact that 1a-cyanocholestanone (derived from 92, [KH3) readily incorporates labeled cyanide (13C=N) under the experimental conditions of the hydrocyanation reaction. 

These compounds often occur as acetate or succinate esters and, for a total analysis, these esters are cleaved by a KOH saponification. Vitamin E is obtained commercially by molecular distillation. This does not provide a pure product, but it does separate vitamin E from most of the other materials associated with it such as chlorophyll, xanthophylls, carotenes, ubiquinol, ubichromenol, steroids, and quinines, but not vitamin A and the beta carotenes. 

The rings are conventionally lettered and numbered as indicated above. However, in actual conformation the basic structure of steroid is not planar. It has also been observed that in the naturally occurring steroidal compounds the substitutions in the rings usually occm at C-3, C-7 and C-11 positions. 

When squalene 2,3-epoxide (2) is cyclized via a chair-boat-chair-boat sequence, the first isolable cyclic intermediate (in plants) is cycloartenol (3) (Fig. 23.6). Cycloartenol proves to be a key intermediate in the synthesis of certain other triterpenes and plant sterols. Many steroids are common [if not ubiquitous, e.g., -sitosterol (4), stigmas-terol (5), and campesterol (6) (Fig. 23.6)] and it is probable that these pathways exist in all plants (Goad and Goodwin, 1973 Grunwald, 1975 1980). Cholesterol (7) occurs in small quantities, but appears to be a universal constituent of plants. This sterol serves as a key intermediate in the synthesis of a number of other steroidal compounds. A new system of numbering sterols was recommended in 1989 (Goad, 1991a). 

A remarkable feature of the Birch reduction of estradiol 3-methyl ether derivatives, as well as of other metal-ammonia reductions, is the extreme rapidity of reaction. Sodium and -butyl alcohol, a metal-alcohol combination having a comparatively slow rate of reduction, effects the reduction of estradiol 3-methyl ether to the extent of 96% in 5 minutes at —33° lithium also effects complete reduction under the same conditions as is to be expected. Shorter reaction times were not studied. At —70°, reduction with sodium occurs to the extent of 56 % in 5 minutes, although reduction with lithium is virtually complete (96%) in the same time. (The slow rates of reduction of compounds of the 5-methoxytetralin type is exemplified by 5-methoxy-tetralin itself with sodium and f-butyl alcohol reduction occurs to the extent of only 50% in 6 hours vs. 99+% with lithium.) The iron catalyzed reaction of sodium with alcohols must be very fast since it competes so well with the rapid Birch reduction. One cannot compensate for the presence of iron in a Birch reduction mixture containing sodium by adding additional metal to extend the reaction time. The iron catalyzed sodium-alcohol reaction is sufficiently rapid that the aromatic steroid still remains largely unreduced. 

Although animals produce steroids, the low concentrations of these compounds does not make these commercially (nor ethically) attractive sources of these substances. Furthermore, they could only serve as sources of naturally occurring steroids. Thus we would not have selected this option. 

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