Steroid Starting Materials

One commercially important class of steroid drugs, it should be noted, is still, interestingly, obtained by isolation from mammahan sources. The best-known drug 

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Although all the main classes of steroids have now been attained by total synthesis, most drugs are in fact, as noted above, prepared by partial synthesis from natural products that contain the steroid nucleus. The bulk of the world s supply of steroid starting material is derived by differing chemical routes from only two species of plants the Mexican yam, a species of... 

Investigation of the possible synthesis of limonin from a steroidal starting material has led to the preparation of the model compound (115).68... 

The driving force behind the development of total syntheses for estrane and to some extent gonanes described in Chapters 2 and 3 lay in the then scarce and hence expensive steroid starting materials. The schemes that were developed made possible the elaboration of derivatives not accessible from estrone, such as gonanes with an additional carbon on the angular methyl at C13. Both androstene-17-dione and testosterone have been prepared by total synthesis. The schemes by which that was accomplished, however, were lengthy and complex. Those syntheses mainly represented a tour deforce for chemical synthesis since they were not competitive with sources of androstanes from pregnenolone or by fermentation. 

Chapter 2 opens with a description of the biosynthesis of naturally occurring steroids. The conversion of two very different phytochemicals to steroids that can be elaborated to potential dmgs follows. The narrative focuses on a discussion of the chemistry whereby these steroidal natural products are modified into steroid starting materials. 

An alternative approach is to make use of a steroidal starting material. The products are then optically active. A major achievement here is the synthesis of the highly functionalized derivative (80) from testosterone (79). The overall yield was low, as expected for a sequence involving some 28 steps. Chenodeoxycholic acid (81) has been converted into the lactone (82). ... 

Some plant and animal steroids occur in large quantities and can be used as inexpensive starting materials for pharmaceutically useful steroid hormones (see table 22). 

The major problem in such conversions is the degradation of the branched carbon side-chain on C-17 which is present in all abundant steroids and lacking in all steroid hormones. The most important starting material used in industry today is diosgenin from the Mexican dioscorea plant. It is degraded by the method of Marker to 16-dehydropregnenolone in 45% total yield. This compound is a key substance in the production of several hormones with anabolic, catabolic, and sexual effects. 

There are three general processes that ate used, as of ca 1996, woddwide for steroid production (/) direct isolation from natural sources, (2) partial synthesis from steroid raw materials that have been isolated from plants and animals, and (J) total synthesis from nonsteroidal starting materials (120). 

Processing Raw Materials. Along with the aforementioned chemical methods of processing steroid raw materials, microbial transformations have been and are used in a number of commercial degradation processes. The microbial degradation of the C17 side chain of the two most common sterols, cholesterol (2) and P-sitosterol (41), is a principal commercial method for the preparation of starting materials in Japan and the... 

Deuterium labeling of certain positions in the steroid nucleus can be a serious problem if suitably functionalized starting materials are not available or if a particular part of the molecule to be labeled is unsuitable for the various reactions described previously in this chapter. In these cases, the only practical solution to this problem is to incorporate the appropriately labeled carbon fragment by synthesis of the desired skeleton. 

During the course of a mass spectrometric study of D-homo-14-hydroxy steroids, it was necessary to prepare the corresponding C-8 deuterium labeled analogs. The preparation of these uncommon steroid derivatives has been achieved by repeating the Torgov total synthesis [(257) (262)] with a deuterium-labeled bicyclic starting material (258). Both of the resulting 14-hydroxy epimers, (261) and (262), exhibited better than 90% isotopic purity. ... 

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