World of Chemistry on Derek H. R. Barton

Derek H. R. Barton had a long and distinguished career in several universities in different countries in the field of natural products chemistry. He was active in structure determination, synthesis, and biosynthesis of a number of complex molecules, and had a special interest in the invention of new and useful chemical reactions. However, he is primarily known for his brilliant understanding of the importance of geometry in the behavior of organic compounds. Barton shared the 1969 Nobel Prize for Chemistry with Odd Hassel, a Norwegian physical chemist, Afor developing and applying the principles of conformation in chemistry, that is, for showing how the shapes of molecules determine their physical and chemical properties.

Derek Harold Richard Barton was born in Gravesend, Kent, England, on September 8, 1918. His grandfather and father were carpenters, and his father, William Thomas Barton, owned a successful lumberyard. Derek was able attend a good private school, but was forced to leave at seventeen without a degree because of his father's sudden death. He helped his mother, Maude Lukes Barton, in lumber business for two years, then enrolled in Gillingham Technical College. After a year at the college, he entered Imperial College, University of London, a center of science in England. He could not afford to live in London, and commuted two hours each way. At Imperial College, he received his B.Sc. with first-class honors in 1940, and his Ph.D. is 1942. He did his graduate thesis work on the synthesis of vinyl chloride (the starting compound for vinyl plastics) under the supervision of two eminent organic chemists, I. M. Heilbron and E. R. H. Jones. After completing his Ph.D., Barton remained at Imperial College to work on the formulation of secret inks for military intelligence, and in 1944 left to work on the synthesis of organic phosphorous compound for a company in Birmingham. After a year in the chemical industry, Barton returned to Imperial College as a junior lecturer in inorganic chemistry. He taught inorganic and physical chemistry for four years until a position in organic chemistry became available.

When Barton returned to Imperial College, he began research on the structures of complex organic compounds, including triterpenoids and steroids. He correlated structures with a physical property of the molecules, molecular rotation, and was able to assigned structures based on a simple physical measurement. During his work with these complex molecules, he became aware of the work of Odd Hassel, who had determined the precise geometry of cyclohexane, a compound that is a ring of six carbon atoms, with each carbon bonded to two hydrogen atoms. Cyclohexane is a structural unit commonly found in sterpods and triterpenoids, and Barton extended Hassel=s structure to the complex molecules. He designed a set of models that accurately represented the actual geometry of steroisa, and had them built in 1948. These models provided Barton with an understanding of the three-dimensional geometry (stereochemistry) of these molecules, which was unknown to other chemists at the time.

Barton's work on steroids had come to the attention of Louis Fieser, a professor at Harvard University, and an eminent authority on steroids. Fieser invited Barton to Harvard as a visiting lecturer, replacing Robert B. Woodward for his sabbatical year. Barton arrived at Harvard in 1949, at a time of intense interest in the chemistry of steroids because their spectacular use in medicine (cortisone therapy) had just been announced. During a seminar lecture by Fieser, in which he discussed unsolved problems in the chemistry of steroids, Barton realized that the precise shape of the molecules, which he knew from his models, could explain the results. He formulated a four- page paper and submitted it to the Swiss journal Experientia, which had a modest readership. This paper provided a stimulus for countless investigations in practical and theoretical chemistry, and was the basis for Barton=s Nobel Prize in 1969. Barton=s description of the influence of molecular geometry on chemistry is called conformational analysis; the principles are readily understood, and are introduced early in undergraduate organic chemistry textbooks. But conformational analysis is also a powerful tool in solving complex biochemical problems, such as enzyme catalysis and pharmacological studies. Although Barton=s contribution to the field was seminal, he left its development to others. He used the principles of conformational analysis to understand the chemistry of the molecules in which he was interested, but his primary concern was always the molecules themselves.

Another of his major interests was one-electron oxidation of organic compounds, which he exploited to explain how complex molecules, such as morphine, are produced in the opium poppy (biosynthesis). Key intermediates in the electron oxidation are reactive species called free radicals, and Barton vigorously explored the use the use of free-radical chemistry in synthesis. Free radicals may be formed in chemical reactions, or by using energy to rupture chemical bonds. The latter method may involve energy from ultraviolet light, and the radicals are thereby generated photochemically. Barton was able to use photochemical reactions effectively in synthesis, and the ABarton reaction was invented in 1958 to synthesize the steroid aldosterone, a hormone that regulates electrolyte balance in the body. At the time, the world supply of aldosterone was only several milligrams, and Barton=s synthesis yielded 60 grams of the hormone by a simple procedure. Barton devoted many of his studies to the invention, rather than the discovery, of new reactions. He and his co- workers contributed many new reagents and procedures that accomplish otherwise difficult chemical transformations.

Barton=s great command of all areas of chemistry enabled him to see connections between what appear to be unrelated facts; he called this ability Agap jumping. For example, his knowledge of chemical physics and steroid chemistry led to the development of conformational analysis. From an early age, he developed the habit of closely reading the literature, and was associated with many other outstanding chemists throughout his career who kept him informed of the latest discoveries. His routine brought him to the laboratory daily to check on the progress of his students and associates, and even in his seventies his work day lasted from three or four in the morning until seven in the evening.

Barton was married to Jeanne Kate Wilkins, and had a son, William Godfrey Lukes Barton. The marriage ended in divorce, and Barton married Christiane Cognet. Barton held several positions in academic institutions, and was also associated with companies in the chemical and pharmaceutical industries. After his return to England from Harvard in 1950, he accepted a position as reader in organic chemistry at Birkbeck College, University of London, where all classes were held in the evening. He was promoted to professor at Birkbeck College in 1953, and left in 1955 to become Regious Professor at the University of Glasgow. After two years, he returned to Imperial College in London as professor of organic chemistry, remaining there for twenty years.

In 1977, at the age of fifty-nine, Barton was appointed director of research of the Centre National de la Recherch Scientifique (CNRS) at the Institut de Chimie de Substances Naturells (ICSN) at Gif-sur-Yvette, France. A year later, he retired from Imperial College. He had an excellent command of the French language, and his French wife was delighted to return home. At the ICSN, Barton continued his work inventing reactions, producing a series of AGif reagents, named for the site of the ICSN. After eight years, Barton retired again, and this time accepted a Distinguished Professorship at Texas A&M University in College Station. He continued to pursue chemical research at his usual active pace in his newly adopted country. Barton had previously visited the United States many times to give lectures and courses, and he spent several summers at the Research Institute for Medicine and Chemistry (RIMAC) in Cambridge, Massachusetts. It was at RIMAC that the Barton reaction for the synthesis of aldosterone was invented. Recognized for his achievement by chemical societies and universities of many nations, he is regarded as one of the most prominent organic chemists of the twentieth century. Barton died in 1998.