During the late 1940s, Woodward synthesized many complex natural products including quinine, cholesterol, cortisone, strychnine, lysergic acid, reserpine, chlorophyll, cephalosporin, and colchicine. With these, Woodward opened up a new era of synthesis, sometimes called the Woodwardian era in which he showed that natural products could be synthesized by careful applications of the principles of physical organic chemistry, and by meticulous planning.
Many of Woodwards syntheses were described as spectacular by his colleagues and before he did them, it was thought by some that it would be impossible to create these substances in the lab. Woodwards syntheses were also described as having an element of art in them, and since then, synthetic chemists have always looked for elegance as well as utility in synthesis. His work also involved the exhaustive use of the then newly developed techniques of infrared spectroscopy and later, nuclear magnetic resonance spectroscopy. Another important feature of Woodwards syntheses was their attention to stereochemistry or the particular configuration of molecules in three-dimensional space. Most natural products of medicinal importance are effective, for example as drugs, only when they possess a specific stereochemistry. This creates the demand for stereoselective synthesis', producing a compound with a defined stereochemistry. While today a typical synthetic route routinely involves such a procedure, Woodward was a pioneer in showing how, with exhaustive and rational planning, one could conduct reactions that were stereoselective. Many of his syntheses involved forcing a molecule into a certain configuration by installing rigid structural elements in it, another tactic that has become standard today. In this regard, especially his syntheses of reserpine and strychnine were landmarks.
During World War II, Woodward was an advisor to the War Production Board on the penicillin project. Although often given credit for proposing the beta-lactam structure of penicillin, it was actually first proposed by chemists at Merck and Edward Abraham at Oxford and then investigated by other groups, as well (e.g., Shell). Woodward at first endorsed an incorrect tricyclic (thiazolidine fused, amino bridged oxazinone) structure put forth by the penicillin group at Peoria. Subsequently, he put his imprimatur on the beta-lactam structure, all of this in opposition to the thiazolidine&ndash;oxazolone structure proposed by Robert Robinson, the then leading organic chemist of his generation. Ultimately, the beta-lactam structure was shown to be correct by Dorothy Hodgkin using X-ray crystallography in 1945.
Woodward also applied the technique of infrared spectroscopy and chemical degradation to determine the structures of complicated molecules. Notable among these structure determinations were santonic acid, strychnine, magnamycin and terramycin. In each one of these cases, Woodward again showed how rational facts and chemical principles, combined with chemical intuition, could be used to achieve the task.
In the early 1950s, Woodward, along with the British chemist Geoffrey Wilkinson, then at Harvard, postulated a novel structure for ferrocene, a compound consisting of a combination of an organic molecule with iron. This marked the beginning of the field of transition metal organometallic chemistry which grew into an industrially very significant field. Wilkinson won the Nobel Prize for this work in 1973, along with Ernst Otto Fischer. Some historians think that Woodward should have shared this prize along with Wilkinson. Remarkably, Woodward himself thought so, and voiced his thoughts in a letter sent to the Nobel Committee.
Woodward won the Nobel Prize in 1965 for his synthesis of complex organic molecules. He had been nominated a total of 111 times from 1946 to 1965. In his Nobel lecture, he described the total synthesis of the antibiotic cephalosporin, and claimed that he had pushed the synthesis schedule so that it would be completed around the time of the Nobel ceremony.