Forgotten Genius

Build a Steroid

As Percy Julian knew only too well, the synthesis of a chemical compound found in nature is a highly complicated process that can take years of research and experimentation. Beginning with a readily available "starter" chemical like diosgenin, which can be extracted from the cheap and plentiful Mexican yam, makes a chemist's job easier. This compound already has the basic chemical structure that all major steroids share. Though it may take numerous chemical reactions to get there, chemists can fashion diosgenin into any steroid, from estrogen for menopausal women to anabolic steroids for athletes. In this feature, watch as diosgenin transforms into adrenal hormone cortisone.—Claudine Ko

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The basic molecular structure of a steroid includes four rings—three six-membered and one five-membered—which are built entirely of carbon atoms. The biological function of a steroid depends on the groups attached to these rings. Diosgenin, for instance, has two additional rings (highlighted here in red). To modify diosgenin's molecular structure to the desired cortisone, our virtual chemist needs to perform a series of chemical reactions.

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Intermediate Compound #1
Multiple steps have been combined to give us our first intermediate compound (16-Dehydropregnenolone acetate, shown here). Note how the red groups have changed. The next steps include oxidation reactions, which add oxygen to the compound. In this case, the chemist uses chromium trioxide (CrO3) and then heats the mixture, which breaks bonds and allows the oxygen to recombine with the steroid.

Wing Structure
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Intermediate Compound #2
After several more steps, the chemist reaches another intermediate compound (11-Dehydrocorticosterone, shown here). The chemist must be precise to prevent any side reactions, which could result in unwanted compounds. To verify that the correct intermediate compound was produced, Percy Julian might have checked its melting point, which is unique to each compound; today chemists use various forms of spectroscopy.

Landing Gear
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Julian made a major chemical breakthrough when he figured out how to add a hydroxyl group at the difficult carbon-11 position, turning the previous intermediate compound into hydrocortisone. But the process took 27 steps. Later, biochemists discovered a fungus that could add the hydroxyl group in a single step.

Tail Assembly
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To produce cortisone, the chemist needs only modify the hydroxyl group in hydrocortisone using another oxidation reaction. When it was first isolated from animals, cortisone—which is used to treat ailments such as rheumatoid arthritis, asthma, and hepatitis—cost about $100 a gram. But after chemists determined how to make it from the Mexican yam, production increased, prices dropped, and the drug became widely available.


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© | Created January 2007