OXYGEN

CARL DJERASSI, STANFORD UNIVERSITY

Oxygen is a tricky subject to be offered on a silver platter. No such platter is large enough to cope with any but the smallest morsels from the giant pantry filled with oxygen-containing goodies. Rather different from an element with a three-digit atomic number, where modest hors d’oeuvres suffice.

One need not be a chemist to know that without oxygen a human life would cease in seconds or minutes rather than decades. But as an organic chemist who has practiced his art for more than half a century, I must concede that without oxygen I would not have published a single paper, because most of my chemical life was spent grazing in steroid pastures. Few classes of organic molecules are as interesting as steroids—covering the gamut from sex hormones, oral contraceptives, bile acids, corticoids, vitamin D, and cardiac glycosides to anabolic drugs of abuse—yet this panoply of biological diversity is based on a single chemical template: the tetracyclic C₁₇H₂₈ steroid skeleton. A thin paperback written solely in two letters (C and H) becomes the steroid “Bible of Life” through addition of a third letter, O, that nature—and occasionally clever chemists—introduce into select places on that template. I shall cite one example.

Arguably the hottest topic in synthetic organic chemistry around 1950 was cortisone—the glamour steroid that had been anointed with the 1950 Nobel Prize in Physiology or Medicine. Pictures of helpless arthritics dancing within days of cortisone administration flooded the media. The fierce competition was described in breathless prose by Harper’s Magazine in 1951: “The new ways of producing cortisone come as the climax to an unrestrained, dramatic race involving a dozen of the largest American drug houses, several leading foreign pharmaceutical manufacturers, three governments, and more research personnel than have worked on any medical problem since penicillin.” In chemical shorthand, it meant discovering how to introduce oxygen into the inaccessible C-11 position of ring C of some readily available plant sterol. And while a single issue in the 1951 Journal of the American Chemical Society recorded the completion of no less than three such successful solutions, the earliest submission date bore the unlikely address, “Syntex, S.A., Laguna Mayran 413”—an industrial area of Mexico City across from a tortilla stand—in marked contrast to the fancy Rahway, N.J., and Cambridge, Mass., addresses of our competitors.

The following year at a Gordon Conference, Robert B. Woodward from Harvard, Lewis H. Sarett from Merck, Gilbert Stork from Columbia, and I from Syntex demonstrated the inherent collegiality of science by composing a spoof under the authorship of F. Nathaniel Greene and Alvina Turnbull titled “Partial Synthesis of Cortisone from Neohamptogenin” (a putative constituent of a potentially inexhaustible source: New Hampshire maple syrup). Whereas our earlier, testosterone-drenched claims in JACS had each trumpeted the “first successful introduction of a C-11 oxygen function into a steroid devoid of functionality in ring C,” we now jointly proclaimed “the first successful introduction of a 3-keto group into an 11-oxygenated steroid devoid of functional groups in ring A.”

The subsequent 40 years of my research career featured a shift from synthesis to the application of physical methods. But even here, steroids were the focus of all our studies and oxygen the key to our successes. If it had not been for our choice of the carbonyl function and its associated strong Cotton effect, we never would have arrived at the generalizations derivable from optical rotatory dispersion and circular dichroism or drawn many mechanistic conclusions from the mass spectra of such oxygen-containing substrates.

But as a chemist turned playwright, let me end with some lines from “Oxygen”—a play I wrote with Roald Hoffmann:

ASTRID: First to the discovery: No one will question that oxygen confers great benefit on mankind, right?

BENGT: Oxygen was good for people before it was “discovered!”

And then Mme. Lavoisier’s conclusion of the play: “Imagine what it means to understand what gives a leaf its color! And how it turns red. What makes a fever fall, a flame burn. Imagine!”

Carl Djerassi is a playwright, novelist, and professor of chemistry emeritus at Stanford University. He has won both the National Medal of Science (for the first synthesis of a steroid oral contraceptive) and the National Medal of Technology (for promoting new approaches to insect control).

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