Robert Burns Woodward
Encyclopedia
Robert Burns Woodward was an American
organic chemist
, considered by many to be the preeminent organic chemist of the twentieth century. He made many key contributions to modern organic chemistry
, especially in the synthesis and structure determination of complex natural products, and worked closely with Roald Hoffmann
on theoretical studies of chemical reactions. He was awarded the Nobel Prize in Chemistry
in 1965.
) and Arthur Chester Woodward, son of Roxbury, Mass. apothecary, Harlow Elliot Woodward. When Robert was one year old, his father died in the flu pandemic of 1918.
From a very early age, Woodward was attracted to and engaged in private study of chemistry
while he attended the public primary and secondary schools of Quincy, Massachusetts
. By the time he entered high school, he had already managed to perform most of the experiments in Ludwig Gattermann
's then widely used textbook of experimental organic chemistry. In 1928, Woodward contacted the Consul-General of the German consulate in Boston, and through him, managed to obtain copies of a few original papers published in German journals. Later, in his Cope lecture, he recalled how he had been fascinated when, among these papers, he chanced upon Diels and Alder's original communication about the Diels-Alder reaction
. Throughout his career, Woodward was to repeatedly and powerfully use and investigate this reaction, both in theoretical and experimental ways. In 1933, he entered the Massachusetts Institute of Technology
(MIT), but neglected his formal studies badly enough to be expelled the next year. MIT readmitted him in 1935, and by 1936 he had received the Bachelor of Science
degree. Only one year later, MIT awarded him the doctorate
, when his classmates were still graduating with their bachelor's degrees. Woodward's doctoral work involved investigations related to the synthesis of the female sex hormone estrone
. MIT required that graduate students have research advisors. Woodward's advisor was Avery A. Ashdown, although it is not clear whether he actually took any of his advice. After a short postdoctoral stint at the University of Illinois, he took a Junior Fellowship at Harvard University
from 1937 to 1938, and remained at Harvard in various capacities for the rest of his life. In the 1960s, Woodward was named Donner Professor of Science, a title that freed him from teaching formal courses so that he could devote his entire time to research.
spectroscopy
in the elucidation of the structure of natural products. Woodward collected together a large amount of empirical data, and then devised a series of rules later called the Woodward's rules
, which could be applied to finding out the structures of new natural substances, as well as non-natural synthesized molecules. The expedient use of newly developed instrumental techniques was a characteristic Woodward exemplified throughout his career, and it marked a radical change from the extremely tedious and long chemical methods of structural elucidation that had been used until then.
In 1944, with his post doctoral researcher, William von Eggers Doering
, Woodward reported the synthesis of the alkaloid
quinine
, used to treat malaria
. Although the synthesis was publicized as a breakthrough in procuring the hard to get medicinal compound from Japanese occupied southeast Asia, in reality it was too long and tedious to adopt on a practical scale. Nevertheless it was a landmark for chemical synthesis. Woodward's particular insight in this synthesis was to realise that the German chemist Paul Rabe had converted a precursor of quinine called quinotoxine to quinine in 1905. Hence, a synthesis of quinotoxine (which Woodward actually synthesized)) would establish a route to synthesizing quinine. When Woodward accomplished this feat, organic synthesis was still largely a matter of trial and error, and nobody thought that such complex structures could actually be constructed. Woodward showed that organic synthesis could be made into a rational science, and that synthesis could be aided by well-established principles of reactivity and structure. This synthesis was the first one in a series of exceedingly complicated and elegant syntheses that he would undertake.
, 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 Woodward's 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. Woodward's 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 Woodward's 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 'stereospecific 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 stereospecific. 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 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
-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. About terramycin, Woodward's colleague and Nobel Laureate Derek Barton said:
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. 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.
. In a remarkable collaboration with his colleague Albert Eschenmoser
in Zurich, a team of almost one hundred students and postdoctoral workers worked for many years on the synthesis of this molecule. The work was finally published in 1973, and it marked a landmark in the history of organic chemistry. The synthesis included almost a hundred steps, and involved the characteristic rigorous planning and analyses that had always characterised Woodward's work. This work, more than any other, convinced organic chemists that the synthesis of any complex substance was possible, given enough time and planning. However, as of 2006, no other total synthesis of Vitamin B12
has been published.
That same year, based on observations that Woodward had made during the B12 synthesis, he and Roald Hoffmann
devised rules (now called the Woodward-Hoffmann rules
) for elucidating the stereochemistry
of the products of organic
reactions
. Woodward formulated his ideas (which were based on the symmetry
properties of molecular orbital
s) based on his experiences as a synthetic organic chemist; he asked Hoffman to perform theoretical calculations to verify these ideas, which were done using Hoffmann's Extended Hückel method
. The predictions of these rules, called the "Woodward-Hoffmann rules" were verified by many experiments. Hoffmann shared the 1981 Nobel Prize for this work along with Kenichi Fukui
, a Japanese chemist who had done similar work using a different approach; Woodward undoubtedly would have received a second Nobel Prize as well had he lived.
Note that a recent paper in the journal Nature describes how mechanical stress can be used to reshape chemical reaction pathways to lead to products that apparently violate Woodward–Hoffman rules.
Woodward Research Institute, based at Basel, Switzerland in 1963. He also became a trustee of his alma mater, MIT, from 1966 to 1971, and of the Weizmann Institute of Science
in Israel
.
Woodward died in Cambridge, Massachusetts
from a heart attack
in his sleep. At the time, he was working on the synthesis of an antibiotic
, erythromycin
. A student of his said about him:
, an artist and technician whom he met at the Polaroid Corp.
This marriage, which lasted until his death in 1979, produced a daughter and a son.
Some of his best-known students include Robert M. Williams (Colorado State), Harry Wasserman (Yale), Yoshito Kishi
(Harvard), Stuart Schreiber
(Harvard), William R. Roush
(Scripps-Florida), Steven A. Benner
(UF), Christopher S. Foote (UCLA), Kendall Houk
(UCLA), porphyrin chemist Kevin M. Smith, and Ronald Breslow
(Columbia University).
Woodward had an encyclopaedic knowledge of chemistry, and an extraordinary memory for detail. Probably the quality that most set him apart from his peers was his remarkable ability to tie together disparate threads of knowledge from the chemical literature and bring them to bear on a chemical problem.
, and enjoyed Scotch whiskey and a martini or two.
, and Merck
.
Other awards include:
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
organic chemist
Organic chemistry
Organic chemistry is a subdiscipline within chemistry involving the scientific study of the structure, properties, composition, reactions, and preparation of carbon-based compounds, hydrocarbons, and their derivatives...
, considered by many to be the preeminent organic chemist of the twentieth century. He made many key contributions to modern organic chemistry
Organic chemistry
Organic chemistry is a subdiscipline within chemistry involving the scientific study of the structure, properties, composition, reactions, and preparation of carbon-based compounds, hydrocarbons, and their derivatives...
, especially in the synthesis and structure determination of complex natural products, and worked closely with Roald Hoffmann
Roald Hoffmann
Roald Hoffmann is an American theoretical chemist who won the 1981 Nobel Prize in Chemistry. He currently teaches at Cornell University in Ithaca, New York.-Escape from the Holocaust:...
on theoretical studies of chemical reactions. He was awarded the Nobel Prize in Chemistry
Nobel Prize in Chemistry
The Nobel Prize in Chemistry is awarded annually by the Royal Swedish Academy of Sciences to scientists in the various fields of chemistry. It is one of the five Nobel Prizes established by the will of Alfred Nobel in 1895, awarded for outstanding contributions in chemistry, physics, literature,...
in 1965.
Early life and education
Woodward was born in Boston, Massachusetts, to Margaret (née Burns, an immigrant from ScotlandScotland
Scotland is a country that is part of the United Kingdom. Occupying the northern third of the island of Great Britain, it shares a border with England to the south and is bounded by the North Sea to the east, the Atlantic Ocean to the north and west, and the North Channel and Irish Sea to the...
) and Arthur Chester Woodward, son of Roxbury, Mass. apothecary, Harlow Elliot Woodward. When Robert was one year old, his father died in the flu pandemic of 1918.
From a very early age, Woodward was attracted to and engaged in private study of chemistry
Chemistry
Chemistry is the science of matter, especially its chemical reactions, but also its composition, structure and properties. Chemistry is concerned with atoms and their interactions with other atoms, and particularly with the properties of chemical bonds....
while he attended the public primary and secondary schools of Quincy, Massachusetts
Quincy, Massachusetts
Quincy is a city in Norfolk County, Massachusetts, United States. Its nicknames are "City of Presidents", "City of Legends", and "Birthplace of the American Dream". As a major part of Metropolitan Boston, Quincy is a member of Boston's Inner Core Committee for the Metropolitan Area Planning Council...
. By the time he entered high school, he had already managed to perform most of the experiments in Ludwig Gattermann
Ludwig Gattermann
Ludwig Gattermann was a German chemist who contributed significantly to both organic and inorganic chemistry.- Early life :...
's then widely used textbook of experimental organic chemistry. In 1928, Woodward contacted the Consul-General of the German consulate in Boston, and through him, managed to obtain copies of a few original papers published in German journals. Later, in his Cope lecture, he recalled how he had been fascinated when, among these papers, he chanced upon Diels and Alder's original communication about the Diels-Alder reaction
Diels-Alder reaction
The Diels–Alder reaction is an organic chemical reaction between a conjugated diene and a substituted alkene, commonly termed the dienophile, to form a substituted cyclohexene system. The reaction can proceed even if some of the atoms in the newly formed ring are not carbon...
. Throughout his career, Woodward was to repeatedly and powerfully use and investigate this reaction, both in theoretical and experimental ways. In 1933, he entered the Massachusetts Institute of Technology
Massachusetts Institute of Technology
The Massachusetts Institute of Technology is a private research university located in Cambridge, Massachusetts. MIT has five schools and one college, containing a total of 32 academic departments, with a strong emphasis on scientific and technological education and research.Founded in 1861 in...
(MIT), but neglected his formal studies badly enough to be expelled the next year. MIT readmitted him in 1935, and by 1936 he had received the Bachelor of Science
Bachelor of Science
A Bachelor of Science is an undergraduate academic degree awarded for completed courses that generally last three to five years .-Australia:In Australia, the BSc is a 3 year degree, offered from 1st year on...
degree. Only one year later, MIT awarded him the doctorate
Doctor of Philosophy
Doctor of Philosophy, abbreviated as Ph.D., PhD, D.Phil., or DPhil , in English-speaking countries, is a postgraduate academic degree awarded by universities...
, when his classmates were still graduating with their bachelor's degrees. Woodward's doctoral work involved investigations related to the synthesis of the female sex hormone estrone
Estrone
Estrone is an estrogenic hormone secreted by the ovary as well as adipose tissue.Estrone is one of several natural estrogens, which also include estriol and estradiol...
. MIT required that graduate students have research advisors. Woodward's advisor was Avery A. Ashdown, although it is not clear whether he actually took any of his advice. After a short postdoctoral stint at the University of Illinois, he took a Junior Fellowship at Harvard University
Harvard University
Harvard University is a private Ivy League university located in Cambridge, Massachusetts, United States, established in 1636 by the Massachusetts legislature. Harvard is the oldest institution of higher learning in the United States and the first corporation chartered in the country...
from 1937 to 1938, and remained at Harvard in various capacities for the rest of his life. In the 1960s, Woodward was named Donner Professor of Science, a title that freed him from teaching formal courses so that he could devote his entire time to research.
Early work
The first major contribution of Woodward's career in the early 1940s was a series of papers describing the application of ultravioletUltraviolet
Ultraviolet light is electromagnetic radiation with a wavelength shorter than that of visible light, but longer than X-rays, in the range 10 nm to 400 nm, and energies from 3 eV to 124 eV...
spectroscopy
Spectroscopy
Spectroscopy is the study of the interaction between matter and radiated energy. Historically, spectroscopy originated through the study of visible light dispersed according to its wavelength, e.g., by a prism. Later the concept was expanded greatly to comprise any interaction with radiative...
in the elucidation of the structure of natural products. Woodward collected together a large amount of empirical data, and then devised a series of rules later called the Woodward's rules
Woodward's rules
Woodward's rules, named after Robert Burns Woodward and also known as Woodward-Fieser rules are several sets of empirically derived rules which attempt to predict the wavelength of the absorption maximum in an ultraviolet-visible spectrum of a given compound...
, which could be applied to finding out the structures of new natural substances, as well as non-natural synthesized molecules. The expedient use of newly developed instrumental techniques was a characteristic Woodward exemplified throughout his career, and it marked a radical change from the extremely tedious and long chemical methods of structural elucidation that had been used until then.
In 1944, with his post doctoral researcher, William von Eggers Doering
William von Eggers Doering
William von Eggers Doering was a Professor Emeritus at Harvard University and the former Chair of its Chemistry Department...
, Woodward reported the synthesis of the alkaloid
Alkaloid
Alkaloids are a group of naturally occurring chemical compounds that contain mostly basic nitrogen atoms. This group also includes some related compounds with neutral and even weakly acidic properties. Also some synthetic compounds of similar structure are attributed to alkaloids...
quinine
Quinine
Quinine is a natural white crystalline alkaloid having antipyretic , antimalarial, analgesic , anti-inflammatory properties and a bitter taste. It is a stereoisomer of quinidine which, unlike quinine, is an anti-arrhythmic...
, used to treat malaria
Malaria
Malaria is a mosquito-borne infectious disease of humans and other animals caused by eukaryotic protists of the genus Plasmodium. The disease results from the multiplication of Plasmodium parasites within red blood cells, causing symptoms that typically include fever and headache, in severe cases...
. Although the synthesis was publicized as a breakthrough in procuring the hard to get medicinal compound from Japanese occupied southeast Asia, in reality it was too long and tedious to adopt on a practical scale. Nevertheless it was a landmark for chemical synthesis. Woodward's particular insight in this synthesis was to realise that the German chemist Paul Rabe had converted a precursor of quinine called quinotoxine to quinine in 1905. Hence, a synthesis of quinotoxine (which Woodward actually synthesized)) would establish a route to synthesizing quinine. When Woodward accomplished this feat, organic synthesis was still largely a matter of trial and error, and nobody thought that such complex structures could actually be constructed. Woodward showed that organic synthesis could be made into a rational science, and that synthesis could be aided by well-established principles of reactivity and structure. This synthesis was the first one in a series of exceedingly complicated and elegant syntheses that he would undertake.
Later work and its impact
Culminating in the 1930s, the British chemists Christopher Ingold and Robert Robinson among others had investigated the mechanisms of organic reactions, and had come up with empirical rules which could predict reactivity of organic molecules. Woodward was perhaps the first synthetic organic chemist who used these ideas as a predictive framework in synthesis. Woodward's style was the inspiration for the work of hundreds of successive synthetic chemists who synthesized medicinally important and structurally complex natural products.Organic syntheses and Nobel Prize
During the late 1940s, Woodward synthesized many complex natural products including quinineQuinine
Quinine is a natural white crystalline alkaloid having antipyretic , antimalarial, analgesic , anti-inflammatory properties and a bitter taste. It is a stereoisomer of quinidine which, unlike quinine, is an anti-arrhythmic...
, cholesterol
Cholesterol
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...
, cortisone
Cortisone
Cortisone is a steroid hormone. It is one of the main hormones released by the adrenal gland in response to stress. In chemical structure, it is a corticosteroid closely related to corticosterone. It is used to treat a variety of ailments and can be administered intravenously, orally,...
, strychnine
Strychnine
Strychnine is a highly toxic , colorless crystalline alkaloid used as a pesticide, particularly for killing small vertebrates such as birds and rodents. Strychnine causes muscular convulsions and eventually death through asphyxia or sheer exhaustion...
, lysergic acid
Lysergic acid
Lysergic acid, also known as D-lysergic acid and -lysergic acid, is a precursor for a wide range of ergoline alkaloids that are produced by the ergot fungus and some plants. Amides of lysergic acid, lysergamides, are widely used as pharmaceuticals and as psychedelic drugs...
, reserpine
Reserpine
Reserpine is an indole alkaloid antipsychotic and antihypertensive drug that has been used for the control of high blood pressure and for the relief of psychotic symptoms, although because of the development of better drugs for these purposes and because of its numerous side-effects, it is rarely...
, chlorophyll
Chlorophyll
Chlorophyll is a green pigment found in almost all plants, algae, and cyanobacteria. Its name is derived from the Greek words χλωρος, chloros and φύλλον, phyllon . Chlorophyll is an extremely important biomolecule, critical in photosynthesis, which allows plants to obtain energy from light...
, cephalosporin
Cephalosporin
The cephalosporins are a class of β-lactam antibiotics originally derived from Acremonium, which was previously known as "Cephalosporium".Together with cephamycins they constitute a subgroup of β-lactam antibiotics called cephems.-Medical use:...
, and colchicine
Colchicine
Colchicine is a medication used for gout. It is a toxic natural product and secondary metabolite, originally extracted from plants of the genus Colchicum...
. 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
Physical organic chemistry
Physical organic chemistry is the study of the interrelationships between structure and reactivity in organic molecules. It can be seen as the study of organic chemistry using tools of physical chemistry such as chemical equilibrium, chemical kinetics, thermochemistry, and quantum chemistry...
, and by meticulous planning.
Many of Woodward's 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. Woodward's 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
Infrared spectroscopy
Infrared spectroscopy is the spectroscopy that deals with the infrared region of the electromagnetic spectrum, that is light with a longer wavelength and lower frequency than visible light. It covers a range of techniques, mostly based on absorption spectroscopy. As with all spectroscopic...
and later, nuclear magnetic resonance
Nuclear magnetic resonance
Nuclear magnetic resonance is a physical phenomenon in which magnetic nuclei in a magnetic field absorb and re-emit electromagnetic radiation...
spectroscopy
Spectroscopy
Spectroscopy is the study of the interaction between matter and radiated energy. Historically, spectroscopy originated through the study of visible light dispersed according to its wavelength, e.g., by a prism. Later the concept was expanded greatly to comprise any interaction with radiative...
. Another important feature of Woodward's syntheses was their attention to stereochemistry
Stereochemistry
Stereochemistry, a subdiscipline of chemistry, involves the study of the relative spatial arrangement of atoms within molecules. An important branch of stereochemistry is the study of chiral molecules....
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 'stereospecific 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 stereospecific. 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
Reserpine
Reserpine is an indole alkaloid antipsychotic and antihypertensive drug that has been used for the control of high blood pressure and for the relief of psychotic symptoms, although because of the development of better drugs for these purposes and because of its numerous side-effects, it is rarely...
and strychnine
Strychnine
Strychnine is a highly toxic , colorless crystalline alkaloid used as a pesticide, particularly for killing small vertebrates such as birds and rodents. Strychnine causes muscular convulsions and eventually death through asphyxia or sheer exhaustion...
were landmarks.
During World War II
World War II
World War II, or the Second World War , was a global conflict lasting from 1939 to 1945, involving most of the world's nations—including all of the great powers—eventually forming two opposing military alliances: the Allies and the Axis...
, Woodward was an advisor to the War Production Board
War Production Board
The War Production Board was established as a government agency on January 16, 1942 by executive order of Franklin D. Roosevelt.The purpose of the board was to regulate the production and allocation of materials and fuel during World War II in the United States...
on the penicillin project. Although often given credit for proposing the beta-lactam
Lactam
A lactam is a cyclic amide. Prefixes indicate how many carbon atoms are present in the ring: β-lactam , γ-lactam , δ-lactam...
structure of penicillin
Penicillin
Penicillin is a group of antibiotics derived from Penicillium fungi. They include penicillin G, procaine penicillin, benzathine penicillin, and penicillin V....
, it was actually first proposed by chemists at Merck
Merck & Co.
Merck & Co., Inc. , also known as Merck Sharp & Dohme or MSD outside the United States and Canada, is one of the largest pharmaceutical companies in the world. The Merck headquarters is located in Whitehouse Station, New Jersey, an unincorporated area in Readington Township...
and Oxford and then investigated by other groups, as well (e.g., Shell). Woodward at first endorsed an incorrect tricyclic (thiazolidine
Thiazolidine
Thiazolidines are a class of heterocyclic organic compounds with a 5-membered saturated ring with a thioether group and an amine group in the 1 and 3 positions, respectively. It is a sulfur analogue of oxazolidine. The drug pioglitazone contains a thiazolidine ring. It is a drug usually indicated...
fused, amino bridged oxazinone) structure put forth by the penicillin group at Peoria. Subsequently, he put his imprimatur
Imprimatur
An imprimatur is, in the proper sense, a declaration authorizing publication of a book. The term is also applied loosely to any mark of approval or endorsement.-Catholic Church:...
on the beta-lactam
Lactam
A lactam is a cyclic amide. Prefixes indicate how many carbon atoms are present in the ring: β-lactam , γ-lactam , δ-lactam...
structure, all of this in opposition to the thiazolidine
Thiazolidine
Thiazolidines are a class of heterocyclic organic compounds with a 5-membered saturated ring with a thioether group and an amine group in the 1 and 3 positions, respectively. It is a sulfur analogue of oxazolidine. The drug pioglitazone contains a thiazolidine ring. It is a drug usually indicated...
-oxazolone
Oxazolone
Oxazolone is a chemical allergen used for immunological experiments, particularly for experiments on delayed type hypersensitivity. Its long chemical name is 4-ethoxymethylene-2-phenyloxazol-5-one and it is commercially available.-References:...
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
X-ray crystallography
X-ray crystallography is a method of determining the arrangement of atoms within a crystal, in which a beam of X-rays strikes a crystal and causes the beam of light to spread into many specific directions. From the angles and intensities of these diffracted beams, a crystallographer can produce a...
in 1945.
Woodward also applied the technique of infrared spectroscopy
Infrared spectroscopy
Infrared spectroscopy is the spectroscopy that deals with the infrared region of the electromagnetic spectrum, that is light with a longer wavelength and lower frequency than visible light. It covers a range of techniques, mostly based on absorption spectroscopy. As with all spectroscopic...
and chemical degradation to determine the structures of complicated molecules. Notable among these structure determinations were santonic acid
Santonic acid
Santonic acid is an organic compound containing both carboxylic acid and ketone functionality.It was synthesized from santonin by base-mediated hydrolysis of a lactone followed by a multistep rearrangement process by R. B. Woodward....
, strychnine
Strychnine
Strychnine is a highly toxic , colorless crystalline alkaloid used as a pesticide, particularly for killing small vertebrates such as birds and rodents. Strychnine causes muscular convulsions and eventually death through asphyxia or sheer exhaustion...
, magnamycin and terramycin. About terramycin, Woodward's colleague and Nobel Laureate Derek Barton said:
- The most brilliant analysis ever done on a structural puzzle was surely the solution (1953) of the terramycin problem. It was a problem of great industrial importance, and hence many able chemists had performed an enormous amount of work trying to determine the structure. There seemed to be too much data to resolve the problem, because a significant number of observations, although experimentally correct, were very misleading. Woodward took a large piece of cardboard, wrote on it all the facts and, by thought alone, deduced the correct structure for terramycin. Nobody else could have done that at the time.
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
Geoffrey Wilkinson
Sir Geoffrey Wilkinson FRS was a Nobel laureate English chemist who pioneered inorganic chemistry and homogeneous transition metal catalysis.-Biography:...
, then at Harvard, postulated a novel structure for ferrocene
Ferrocene
Ferrocene is an organometallic compound with the formula Fe2. It is the prototypical metallocene, a type of organometallic chemical compound consisting of two cyclopentadienyl rings bound on opposite sides of a central metal atom. Such organometallic compounds are also known as sandwich compounds...
, a compound consisting of a combination of an organic molecule with iron. This marked the beginning of the field of transition metal
Transition metal
The term transition metal has two possible meanings:*The IUPAC definition states that a transition metal is "an element whose atom has an incomplete d sub-shell, or which can give rise to cations with an incomplete d sub-shell." Group 12 elements are not transition metals in this definition.*Some...
organometallic chemistry
Organometallic chemistry
Organometallic chemistry is the study of chemical compounds containing bonds between carbon and a metal. Since many compounds without such bonds are chemically similar, an alternative may be compounds containing metal-element bonds of a largely covalent character...
which grew into an industrially very significant field. Wilkinson won the Nobel Prize for this work in 1973, along with Ernst Otto Fischer
Ernst Otto Fischer
Ernst Otto Fischer was a German chemist who won the Nobel Prize for pioneering work in the area of organometallic chemistry.-Early life:...
. 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. In his Nobel lecture, he described the total synthesis of the antibiotic cephalosporin
Cephalosporin
The cephalosporins are a class of β-lactam antibiotics originally derived from Acremonium, which was previously known as "Cephalosporium".Together with cephamycins they constitute a subgroup of β-lactam antibiotics called cephems.-Medical use:...
, and claimed that he had pushed the synthesis schedule so that it would be completed around the time of the Nobel ceremony.
B12 synthesis and Woodward-Hoffmann rules
In the early 1960s, Woodward began work on what was the most complex natural product synthesized to date- vitamin B12Vitamin B12
Vitamin B12, vitamin B12 or vitamin B-12, also called cobalamin, is a water-soluble vitamin with a key role in the normal functioning of the brain and nervous system, and for the formation of blood. It is one of the eight B vitamins...
. In a remarkable collaboration with his colleague Albert Eschenmoser
Albert Eschenmoser
Albert Eschenmoser is a Swiss chemist working at the ETH Zurich and The Scripps Research Institute.His work together with Lavoslav Ružička on terpenes and the postulation of squalene cyclization to form lanosterol improved the insight into steroid biosynthesis.In the early 1960s, Eschenmoser began...
in Zurich, a team of almost one hundred students and postdoctoral workers worked for many years on the synthesis of this molecule. The work was finally published in 1973, and it marked a landmark in the history of organic chemistry. The synthesis included almost a hundred steps, and involved the characteristic rigorous planning and analyses that had always characterised Woodward's work. This work, more than any other, convinced organic chemists that the synthesis of any complex substance was possible, given enough time and planning. However, as of 2006, no other total synthesis of Vitamin B12
Vitamin B12 total synthesis
Vitamin B12 total synthesis in chemistry describes the total synthesis of the complex biomolecule vitamin B12. A method first reported by the groups of Robert Burns Woodward and Albert Eschenmoser in 1973 is considered a classic in this research field....
has been published.
That same year, based on observations that Woodward had made during the B12 synthesis, he and Roald Hoffmann
Roald Hoffmann
Roald Hoffmann is an American theoretical chemist who won the 1981 Nobel Prize in Chemistry. He currently teaches at Cornell University in Ithaca, New York.-Escape from the Holocaust:...
devised rules (now called the Woodward-Hoffmann rules
Woodward-Hoffmann rules
The Woodward–Hoffmann rules devised by Robert Burns Woodward and Roald Hoffmann are a set of rules in organic chemistry predicting the stereochemistry of pericyclic reactions based on orbital symmetry. These include electrocyclic reactions, cycloadditions , sigmatropic reactions, and group transfer...
) for elucidating the stereochemistry
Stereochemistry
Stereochemistry, a subdiscipline of chemistry, involves the study of the relative spatial arrangement of atoms within molecules. An important branch of stereochemistry is the study of chiral molecules....
of the products of organic
Organic chemistry
Organic chemistry is a subdiscipline within chemistry involving the scientific study of the structure, properties, composition, reactions, and preparation of carbon-based compounds, hydrocarbons, and their derivatives...
reactions
Chemical reaction
A chemical reaction is a process that leads to the transformation of one set of chemical substances to another. Chemical reactions can be either spontaneous, requiring no input of energy, or non-spontaneous, typically following the input of some type of energy, such as heat, light or electricity...
. Woodward formulated his ideas (which were based on the symmetry
Symmetry
Symmetry generally conveys two primary meanings. The first is an imprecise sense of harmonious or aesthetically pleasing proportionality and balance; such that it reflects beauty or perfection...
properties of molecular orbital
Molecular orbital
In chemistry, a molecular orbital is a mathematical function describing the wave-like behavior of an electron in a molecule. This function can be used to calculate chemical and physical properties such as the probability of finding an electron in any specific region. The term "orbital" was first...
s) based on his experiences as a synthetic organic chemist; he asked Hoffman to perform theoretical calculations to verify these ideas, which were done using Hoffmann's Extended Hückel method
Extended Huckel method
The extended Hückel method is a semiempirical quantum chemistry method, developed by Roald Hoffmann since 1963. It is based on the Hückel method but, while the original Hückel method only considers pi orbitals, the extended method also includes the sigma orbitals.The extended Hückel method can be...
. The predictions of these rules, called the "Woodward-Hoffmann rules" were verified by many experiments. Hoffmann shared the 1981 Nobel Prize for this work along with Kenichi Fukui
Kenichi Fukui
Kenichi Fukui was a Japanese chemist.Kenichi Fukui was co-recipient of the Nobel Prize in Chemistry in 1981 with Roald Hoffmann, for their independent investigations into the mechanisms of chemical reactions...
, a Japanese chemist who had done similar work using a different approach; Woodward undoubtedly would have received a second Nobel Prize as well had he lived.
Note that a recent paper in the journal Nature describes how mechanical stress can be used to reshape chemical reaction pathways to lead to products that apparently violate Woodward–Hoffman rules.
Woodward Institute and later life
While at Harvard, Woodward took on the directorship of theWoodward Research Institute, based at Basel, Switzerland in 1963. He also became a trustee of his alma mater, MIT, from 1966 to 1971, and of the Weizmann Institute of Science
Weizmann Institute of Science
The Weizmann Institute of Science , known as Machon Weizmann, is a university and research institute in Rehovot, Israel. It differs from other Israeli universities in that it offers only graduate and post-graduate studies in the sciences....
in Israel
Israel
The State of Israel is a parliamentary republic located in the Middle East, along the eastern shore of the Mediterranean Sea...
.
Woodward died in Cambridge, Massachusetts
Cambridge, Massachusetts
Cambridge is a city in Middlesex County, Massachusetts, United States, in the Greater Boston area. It was named in honor of the University of Cambridge in England, an important center of the Puritan theology embraced by the town's founders. Cambridge is home to two of the world's most prominent...
from a heart attack
Myocardial infarction
Myocardial infarction or acute myocardial infarction , commonly known as a heart attack, results from the interruption of blood supply to a part of the heart, causing heart cells to die...
in his sleep. At the time, he was working on the synthesis of an antibiotic
Antibiotic
An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...
, erythromycin
Erythromycin
Erythromycin is a macrolide antibiotic that has an antimicrobial spectrum similar to or slightly wider than that of penicillin, and is often used for people who have an allergy to penicillins. For respiratory tract infections, it has better coverage of atypical organisms, including mycoplasma and...
. A student of his said about him:
- I owe a lot to R. B. Woodward. He showed me that one could attack difficult problems without a clear idea of their outcome, but with confidence that intelligence and effort would solve them. He showed me the beauty of modern organic chemistry, and the relevance to the field of detailed careful reasoning. He showed me that one does not need to specialize. Woodward made great contributions to the strategy of synthesis, to the deduction of difficult structures, to the invention of new chemistry, and to theoretical aspects as well. He taught his students by example the satisfaction that comes from total immersion in our science. I treasure the memory of my association with this remarkable chemist.
Family
In 1938 he married Irja Pullman; they had two daughters. In 1946, he married Eudoxia MullerEudoxia Woodward
Eudoxia Muller Woodward was an American artist and scientist. She was known for her work with Edwin H. Land at the Polaroid Corporation, where her research helped produce the Vectograph and the SX-70....
, an artist and technician whom he met at the Polaroid Corp.
Polaroid Corporation
Polaroid Corporation is an American-based international consumer electronics and eyewear company, originally founded in 1937 by Edwin H. Land. It is most famous for its instant film cameras, which reached the market in 1948, and continued to be the company's flagship product line until the February...
This marriage, which lasted until his death in 1979, produced a daughter and a son.
Publications
During his lifetime Woodward authored or coauthored almost 200 publications, of which 85 are full papers, the remainder comprising preliminary communications, the text of lectures, and reviews. The pace of his scientific activity soon outstripped his capacity to publish all experimental details, and much of the work in which he participated was not published until a few years after his death. Woodward trained more than two hundred talented Ph.D. students and postdoctoral workers, many of whom later went on to distinguished careers.Some of his best-known students include Robert M. Williams (Colorado State), Harry Wasserman (Yale), Yoshito Kishi
Yoshito Kishi
Yoshito Kishi is the Morris Loeb Professor of Chemistry at Harvard University. He is known for his contributions to the sciences of organic synthesis and total synthesis....
(Harvard), Stuart Schreiber
Stuart Schreiber
Stuart L. Schreiber is a scientist at Harvard University and the Broad Institute. He has been a pioneer in a field of research named chemical biology for over 20 years. His name is closely associated with the increasingly common use of small molecules as probes of biology and medicine...
(Harvard), William R. Roush
William R. Roush
William R. Roush is an American organic chemist. He was born on February 20, 1952 in Chula Vista, California. Roush studied chemistry at the University of California Los Angeles and Harvard University . Following a year postdoctoral appointment at Harvard, he joined that faculty at the...
(Scripps-Florida), Steven A. Benner
Steven Albert Benner
Steven A. Benner is a former V.T. & Louise Jackson Distinguished Professor of Chemistry at the University of Florida Department of Chemistry. He was also a faculty member in the Department of Molecular Cell Biology....
(UF), Christopher S. Foote (UCLA), Kendall Houk
Kendall Houk
Kendall Newcomb Houk is a Professor of Chemistry and the Saul Winstein Chair in Organic Chemistry at the University of California, Los Angeles.-Education:...
(UCLA), porphyrin chemist Kevin M. Smith, and Ronald Breslow
Ronald Breslow
Ronald C. D. Breslow is an American chemist from Rahway, New Jersey. He is currently University Professor at Columbia University, where he is based in the Department of Chemistry and affiliated with the Departments of Biological Sciences and Pharmacology; he has also been on the faculty of its...
(Columbia University).
Woodward had an encyclopaedic knowledge of chemistry, and an extraordinary memory for detail. Probably the quality that most set him apart from his peers was his remarkable ability to tie together disparate threads of knowledge from the chemical literature and bring them to bear on a chemical problem.
Idiosyncracies
His lectures were legendary and frequently used to last for three or four hours. [His longest known lecture defined the unit of time known as the "Woodward", and thereafter his other lectures were deemed to be so many "milli-Woodwards" long!] In many of these, he eschewed the use of slides and used to draw beautiful structures by using multicolored chalk. As a result, it was always easy to take good notes at a Woodward lecture. Typically, to begin a lecture, Woodward would arrive and lay out two large white handkerchiefs on the countertop. Upon one would be four or five colors of chalk (new pieces), neatly sorted by color, in a long row. Upon the other handkerchief would be placed an equally impressive row of cigarettes. The previous cigarette would be used to light the next one. His famous Thursday seminars at Harvard often lasted well into the night. He had a fixation with blue, and all his suits, his car, and even his parking space were coloured in blue. In one of his laboratories, his students hung a large black and white photograph of the master from the ceiling, complete with a large blue "tie" appended. There it hung for some years (early 1970s), until scorched in a minor laboratory fire. He detested exercise, could get along with only a few hours of sleep every night, was a heavy smokerChain smoking
Chain smoking is the practice of lighting a new cigarette for personal consumption immediately after one that is finished, sometimes using the finished cigarette to light the next one. It is a common form of addiction.-Causes:...
, and enjoyed Scotch whiskey and a martini or two.
Honors/Awards
For his work, Woodward received many awards, honors and honorary doctorates, including election to the National Academy of Sciences in 1953, and membership in academies around the world. He was also a consultant to many companies such as Polaroid, PfizerPfizer
Pfizer, Inc. is an American multinational pharmaceutical corporation. The company is based in New York City, New York with its research headquarters in Groton, Connecticut, United States...
, and Merck
Merck & Co.
Merck & Co., Inc. , also known as Merck Sharp & Dohme or MSD outside the United States and Canada, is one of the largest pharmaceutical companies in the world. The Merck headquarters is located in Whitehouse Station, New Jersey, an unincorporated area in Readington Township...
.
Other awards include:
- John Scott MedalJohn Scott AwardThe John Scott Legacy Medal and Premium, created in 1816, is a medal presented to men and women whose inventions improved the "comfort, welfare, and happiness of human kind" in a significant way...
, from the Franklin InstituteFranklin InstituteThe Franklin Institute is a museum in Philadelphia, Pennsylvania, and one of the oldest centers of science education and development in the United States, dating to 1824. The Institute also houses the Benjamin Franklin National Memorial.-History:On February 5, 1824, Samuel Vaughn Merrick and...
and City of Philadelphia, 1945 - Baekeland Medal, from the North Jersey Section of the American Chemical SocietyAmerican Chemical SocietyThe American Chemical Society is a scientific society based in the United States that supports scientific inquiry in the field of chemistry. Founded in 1876 at New York University, the ACS currently has more than 161,000 members at all degree-levels and in all fields of chemistry, chemical...
, 1955 - DavyHumphry DavySir Humphry Davy, 1st Baronet FRS MRIA was a British chemist and inventor. He is probably best remembered today for his discoveries of several alkali and alkaline earth metals, as well as contributions to the discoveries of the elemental nature of chlorine and iodine...
Medal, from the Royal SocietyRoyal SocietyThe Royal Society of London for Improving Natural Knowledge, known simply as the Royal Society, is a learned society for science, and is possibly the oldest such society in existence. Founded in November 1660, it was granted a Royal Charter by King Charles II as the "Royal Society of London"...
in 1959 - Roger AdamsRoger AdamsRoger Adams was an American organic chemist. He is best-known for the eponymous Adams' catalyst, and his work did much to determine the composition of naturally occurring substances such as complex vegetable oils and plant alkaloids...
Medal, from the American Chemical Society in 1961 - Pius XI Gold Medal, from the Pontifical Academy of Sciences in 1969
- National Medal of ScienceNational Medal of ScienceThe National Medal of Science is an honor bestowed by the President of the United States to individuals in science and engineering who have made important contributions to the advancement of knowledge in the fields of behavioral and social sciences, biology, chemistry, engineering, mathematics and...
from the United States of AmericaUnited StatesThe United States of America is a federal constitutional republic comprising fifty states and a federal district...
in 1964 ("For an imaginative new approach to the synthesis of complex organic molecules and, especially, for his brilliant syntheses of strychnine, reserphine, lysergic acid, and chlorophyll.") - Nobel Prize in ChemistryNobel Prize in ChemistryThe Nobel Prize in Chemistry is awarded annually by the Royal Swedish Academy of Sciences to scientists in the various fields of chemistry. It is one of the five Nobel Prizes established by the will of Alfred Nobel in 1895, awarded for outstanding contributions in chemistry, physics, literature,...
in 1965 - Willard Gibbs Medal from the ChicagoChicagoChicago is the largest city in the US state of Illinois. With nearly 2.7 million residents, it is the most populous city in the Midwestern United States and the third most populous in the US, after New York City and Los Angeles...
Section of the American Chemical Society in 1967 - Lavoisier Medal from the Société Chimique de FranceSociété Chimique de FranceThe Société Chimique de France is a learned society and professional association founded in 1857 to represent the interests of French chemists in a variety of ways in local, national and international contexts.-History:...
in 1968 - The Order of the Rising SunOrder of the Rising SunThe is a Japanese order, established in 1875 by Emperor Meiji of Japan. The Order was the first national decoration awarded by the Japanese Government, created on April 10, 1875 by decree of the Council of State. The badge features rays of sunlight from the rising sun...
, Second Class from the Emperor of JapanJapanJapan is an island nation in East Asia. Located in the Pacific Ocean, it lies to the east of the Sea of Japan, China, North Korea, South Korea and Russia, stretching from the Sea of Okhotsk in the north to the East China Sea and Taiwan in the south...
in 1970 - Hanbury Memorial Medal from The Pharmaceutical Society of Great BritainGreat BritainGreat Britain or Britain is an island situated to the northwest of Continental Europe. It is the ninth largest island in the world, and the largest European island, as well as the largest of the British Isles...
in 1970 - Pierre Bruylants Medal from the University of Louvain in 1970
- AMA Scientific Achievement AwardAMA Scientific Achievement AwardThe AMA Scientific Achievement Award is awarded by American Medical Association. It may be given to either physicians or non-physician scientists who have contributed significantly to the field of medical science...
in 1971 - Cope AwardArthur C. Cope AwardThe Arthur C. Cope Award is a prize awarded for achievement in the field of organic chemistry research. It is generally considered one of the highest honors in the field. It is sponsored by the Arthur C. Cope Fund, and has been awarded since 1973 by the American Chemical Society.Recipients...
from the American Chemical Society, shared with Roald HoffmannRoald HoffmannRoald Hoffmann is an American theoretical chemist who won the 1981 Nobel Prize in Chemistry. He currently teaches at Cornell University in Ithaca, New York.-Escape from the Holocaust:...
Honorary degrees
Woodward also received over twenty honorary degrees, including honorary doctorates from the following universities:- Wesleyan UniversityWesleyan UniversityWesleyan University is a private liberal arts college founded in 1831 and located in Middletown, Connecticut. According to the Carnegie Foundation for the Advancement of Teaching, Wesleyan is the only Baccalaureate College in the nation that emphasizes undergraduate instruction in the arts and...
in 1945; - Harvard UniversityHarvard UniversityHarvard University is a private Ivy League university located in Cambridge, Massachusetts, United States, established in 1636 by the Massachusetts legislature. Harvard is the oldest institution of higher learning in the United States and the first corporation chartered in the country...
in 1957; - University of CambridgeUniversity of CambridgeThe University of Cambridge is a public research university located in Cambridge, United Kingdom. It is the second-oldest university in both the United Kingdom and the English-speaking world , and the seventh-oldest globally...
in 1964; - Brandeis UniversityBrandeis UniversityBrandeis University is an American private research university with a liberal arts focus. It is located in the southwestern corner of Waltham, Massachusetts, nine miles west of Boston. The University has an enrollment of approximately 3,200 undergraduate and 2,100 graduate students. In 2011, it...
in 1965; - Technion Israel Institute of Technology in HaifaHaifaHaifa is the largest city in northern Israel, and the third-largest city in the country, with a population of over 268,000. Another 300,000 people live in towns directly adjacent to the city including the cities of the Krayot, as well as, Tirat Carmel, Daliyat al-Karmel and Nesher...
in 1966; - University of Western OntarioUniversity of Western OntarioThe University of Western Ontario is a public research university located in London, Ontario, Canada. The university's main campus covers of land, with the Thames River cutting through the eastern portion of the main campus. Western administers its programs through 12 different faculties and...
in CanadaCanadaCanada is a North American country consisting of ten provinces and three territories. Located in the northern part of the continent, it extends from the Atlantic Ocean in the east to the Pacific Ocean in the west, and northward into the Arctic Ocean...
in 1968; - University of Louvain in BelgiumBelgiumBelgium , officially the Kingdom of Belgium, is a federal state in Western Europe. It is a founding member of the European Union and hosts the EU's headquarters, and those of several other major international organisations such as NATO.Belgium is also a member of, or affiliated to, many...
, 1970.
Sources
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- Robert Burns Woodward: Architect and Artist in the World of Molecules; Otto Theodor Benfey, Peter J. T. Morris, Chemical Heritage Foundation, April 2001.
- Robert Burns Woodward and the Art of Organic Synthesis: To Accompany an Exhibit by the Beckman Center for the History of Chemistry (Publication / Beckman Center for the History of Chemistry); Mary E. Bowden; Chemical Heritage Foundation, March 1992
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External links
- Robert Burns Woodward
- Video podcast of Robert Burns Woodward talking about cephalosporin
- Robert Burns Woodward Patents Woefully incomplete list; see Discussion pages.
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