Pregnane derivatives biosynthesis

Lindemann, P and Luckner, M. (1997) Biosynthesis of pregnane derivatives in somatic embryos of Digitalis lanata. Phytochemistry, 46, 507-13. 

The bufatenolides (90) probably have a biosynthesis in plants similar to the cardenolides. Pregnenolone is incorporated into hellebrin [(90) with (89 Sp-OH, 19-oxo)] and scilliroside [(90) with (89 A )]. However, in the toad Bufo) cholanic acid derivatives are far better precursors than pregnane derivatives. This suggests that all five carbon atoms of the enolester ring (90) may be derived from cholesterol in the toad compared with only two in plants. In the toad, marinobufagin [(90) with (89 5 -OH, 14,15-oxide)] is the precursor of telecinobufagin [(90) with (89 5 -OH)]. ... 

The main topic of this review will be the summarization of our present knowledge of how pregnenolone is formed from cholesterol in steroid-producing tissues. Since pregnane derivatives are so widely found in nature, some attention will also be paid to the type of C21 steroids isolated, to their distribution, to their precursors and steroids closely related to them, and to the distribution of the enzymes concerned with their formation. Among the major contributions responsible for the advances made in this field, one may list the preparation of appropriate steroid substrate intermediates, both unlabeled and labeled, and the development of analytical techniques for their chromatographic separation and measurement. As in all major fields of science there has been an exponential increase in published material on steroid biosynthesis, not without considerable duplication. However, since various authors look at the subject from dif-... 

The first glimpse into species differences regarding the biosynthesis of pregnane derivatives was afforded by Bush (1953), who demonstrated that various species differed in their adrenal secretion of cortisol and corticosterone. Interesting species differences have been observed by Idler and co-workers in fish. Thus, the Elasmo-branchii alone were found to possess la-hydroxycorticosterone in their blood stream and the responsible corticosterone la-hydroxylase in their interrenal tissue (Idler et al., 1969). la-Hydroxycorticosterone had approximately 80% of the sodium transport activity across the isolated toad bladder exhibited by d-aldosterone (Grimm et al., 1969). 

The biosynthesis of pregnenelone (112) in mammals has been well documented [1] it is known to be produced from cholesterol (1) via its 20,22-dihydroxy derivative (121) (Scheme 19A). The origin of 112 has been investigated in the sponge Amphimedon compressa. At the present time it is not known whether cholesterol and its 20,22-dihydroxy derivative serve as precursors for this pregnane in A. compressa however a new pathway (Scheme 19B) has been found to operate [89]. This involves the conversion of 22-dehydro sterols (e.g. stigmasterol, 122) to pregnenelone. The mechanism is believed to... 

This direct synthesis of steroidal pyrones should make a variety of structures related to the lucibufagins (as well as to the toad-derived bufadienolides) readily available for biological investigation for the first time. How the insects themselves manage to obtain their defensive pregnanes and steroidal pyrones remains a mystery, since insects are generally considered to lack the enzymatic machinery essential for steroid biosynthesis (19). In fact, we do not yet know whether these insect defensive steroids are produced de novo or whether they are derived... 

---