Progesterone from diosgenin

Figure 10.1 An outline of the synthesis of progesterone from diosgenin...

The most viable method for obtaining larger amounts of steroid hormones is to start with some readily available natural product with a structure that is similar to a steroid and convert it to the desired compound. Russell Marker, a professor at Pennsylvania State University, developed such a method to prepare progesterone from diosgenin, a material that is readily available from Mexican yams. His synthesis is outlined in Figure 28.9. However, he could not interest a major pharmaceutical company in his process, so in 1944 he founded his own company, Syntex, in Mexico City to develop it. 

One way to accomplish the isomerization of a double bond into conjugation with a carbonyl group, one of the reactions needed for the last part of the synthesis of progesterone from diosgenin, is to treat the compound with base as shown in the following equation. Show a mechanism for this reaction. 

Diosgenin, isolated from Mexican yams and used as precursor of progesterone in its semisynthesis as an early oral contraceptive... 

The two major types of steroidal sapogenin are diosgenin and hecogenin. Steroidal saponins are used in the commercial production of sex hormones for clinical use. For example, progesterone is derived from diosgenin. 

Powdered Dioscorea (wild yam) root or extract is also marketed to treat the symptoms of menopause as an alternative to hormone replacement therapy (see page 279). Although there is a belief that this increases levels of progesterone, which is then used as a biosynthetic precursor of other hormones, there is no evidence that diosgenin is metabolized in the human body to progesterone, and any beneficial effects may arise from diosgenin itself. 

The discovery of this stereoselective hydroxylation at C-11 and the introduction of diosgenin as a cheap raw material had dramatic effects in reducing the cost of steroid hormones. Thus in the early 1950 s, the price of progesterone dropped within just three years from 80 to 3/g. In its turn cortisone cost about 200/g in 1949 whereas today its cost is less than l/g. Several other steroids are also prepared by processes which include a microbiological oxidation step among them, cortexone and fluocortolone. 

For the formation of testosterone (51), androsten-5-3-ol-17-one (50) obtained by oxidation from cholesterol was employed although it was also derivable from diosgenin by way of l6-dehydropregnenolone as described for the preparation of progesterone. The synthesis of the androgen followed the route shown and the acetate was isolated in an overall yield of nearly 40% in the Syntex procedure from the androstenone intermediate. 

Pregnenolone from diosgenin can be converted to progesterone in two straightforward steps. Thus, catalytic hydrogenation of 1-1 leads to the dihydro derivative 1-2 (Scheme 6.1). Oppenauer reaction provides the carbonyl group... 

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