Organic chemistry in the 20th century

No specialty was more affected by these changes than organic chemistry. The case of the American chemist Robert B. Woodward may be taken as illustrative. Woodward was the finest master of classical organic chemistry, but he was also a leader in aggressively exploiting new instrumentation, especially infrared, ultraviolet, and NMR spectrometry. His stock in trade was “total synthesis,” the creation of a (usually natural) organic substance in the laboratory, beginning with the simplest possible starting materials. Among the compounds that he and his collaborators synthesized were alkaloids such as quinine and strychnine, antibiotics such as tetracycline, and the extremely complex molecule chlorophyll. Woodward’s highest accomplishment in this field actually came six years after his receipt of the Nobel Prize for Chemistry in 1965: the synthesis of vitamin B12, a notable landmark in complexity. Progress continued apace after Woodward’s death. By 1994 a group at Harvard University had succeeded in synthesizing an extraordinarily challenging natural product, called palytoxin, that had more than 60 stereocentres.

These total syntheses have had both practical and scientific spin-offs. Before the “instrumental revolution,” syntheses were often or even usually done to prove molecular structures. Today they are a central element of the search for new drugs. They can also illuminate theory. Together with a young Polish-born American chemical theoretician named Roald Hoffmann, Woodward followed up hints from the B12 synthesis that resulted in the formulation of orbital symmetry rules. These rules seemed to apply to all thermal or photochemical organic reactions that occur in a single step. The simplicity and accuracy of the predictions generated by the new rules, including highly specific stereochemical details of the product of the reaction, provided an invaluable tool for synthetic organic chemists.

Stereochemistry, born toward the end of the 19th century, received steadily increasing attention throughout the 20th century. The three-dimensional details of molecular structure proved to be not only critical to chemical (and biochemical) function but also extraordinarily difficult to analyze and synthesize. Several Nobel Prizes in the second half of the century—those awarded to Derek Barton of Britain, John Cornforth of Australia, Vladimir Prelog of the Soviet Union, and others—were given partially or entirely to honour stereochemical advances. Also important in this regard was the American Elias J. Corey, awarded the Nobel Prize for Chemistry in 1990, who developed what he called retrosynthetic analysis, assisted increasingly by special interactive computer software. This approach transformed synthetic organic chemistry. Another important innovation was combinatorial chemistry, in which scores of compounds are simultaneously prepared—all permutations on a basic type—and then screened for physiological activity.