From Diosgenin

For a long time several steroid hormones have been synthesized from diosgenin (16) isolated from Dioscoria species growing in Mexico. Nowadays, China has... 

Today, a variety of therapeutic estrogens are produced semisynthetically from estrogen intermediates synthesized from diosgenin and other natural precursors. Two semisynthetic, orally active estrogens are ethinyl estradiol (5.27) and its 3-methyl ether (5.28, mestranol). Both of these are used in oral contraceptives (see section 5.8.3). Quinestrol (5.29) is another semisynthetic estrogen. The most important property of the semisynthetic estrogens is their increased oral effectiveness. 

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. 

An alternative sequence from diosgenin to hydrocortisone has been devised, making use of another microbiological hydroxylation, this time a direct 11 p-hydroxylation of the steroid ring system (Figure 5.121). The fungus Curvu-laria lunata is able to 11 p-hydroxylate cortex-olone to hydrocortisone in yields of about 60%. 

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

Later the estrone produced for commercial purposes was obtained from diosgenin. Diosgenin was first oxidized to its l,4,6-triene-3-one derivative, which was aromatized by pyrolysis at 500-600°C,50 subjected to the Marker degradation and the 17-acetyl group removed by Beckmann rearrangement of the 20-oxime. The overall Syntex process51 for the manufacture of Norethindrone from diosgenin (XVIII) is outlined in Scheme 5. 

Overcoming a Health/Safety issue in the manufacture of a betamethasone intermediate from Diosgenin in Mexico City, and the evaluation of newer raw materials derived from plants. 

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. 

Figure 31 Synthesis of cortisone acetate from diosgenin.

The cyclic enolic ether, furostene (246), derived from diosgenin, was opened with substitution at C(16) by aqueous hydrobromic acid, to give the 16-bromo-cholestan-22-one (247). °... 

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. 

Fermentation in its simplest forms, such as the production of bread or wine, is very old technology. In its application with recombinant DNA to produce pharmacologically active proteins (erythropoetin, human growth hormone, human insulin), it is central to the modem biotechnological revolution. In between, it is the method for production of antibiotics and vitamin B12 and provides a step in the production of vitamin C and the synthesis of cortisone from diosgenin. 

Steroid 18 was prepared from diosgenin in 6 steps and 14% yield (Scheme 8). The configuration of the la-OH (22) could not be inverted by using SN2-type reactions, probably owing to the stereohindrance of this position. Therefore an oxidation-reduction sequence was used to epimerize the la-OH (22 18). The trans-... 

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... 

It has also been synthesized from diosgenine by Marker et al. (1940-1941) whieh will be discussed... 

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