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Charles William Shoppee. 4 February 1904 20 October 1994

Lewis N. Mander Biogr. Mems Fell. R. Soc. 2003 49, 495-507 doi: 10.1098/rsbm.2003.0029

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CHARLES WILLIAM SHOPPEE

4 February 1904 20 October 1994

Biogr. Mems Fell. R. Soc. Lond. 49, 495507 (2003)

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CHARLES WILLIAM SHOPPEE

4 February 1904 20 October 1994 Elected FRS 1956 BY LEWIS N. MANDER FRS
Research School of Chemistry, Australian National University, Canberra ACT 0200, Australia

INTRODUCTION
Charles Shoppee was a major figure in research into the steroid family of organic compounds. After an extensive grounding in mechanistic organic chemistry with such major figures as Sir Jocelyn Thorpe FRS at Imperial College and Sir Christopher Ingold FRS at the University of Leeds, Shoppee spent the war years in Basel working with Tadeus Reichstein (ForMemRS 1952). There he began to apply reaction mechanistic concepts to the reactions of natural products, particularly steroids, in which he was in the vanguard of a huge and widespread activity prompted, in part, by the pharmaceutical industrys interests in these important compounds. However, in additional to their therapeutic potential they provided a rigid template on which one could explore aspects of structure determination, synthesis, mechanism and stereochemistry. After the war, Shoppee spent a brief period in London before taking up the chair of chemistry at the University of Wales, Swansea, where he built up the research strengths of the Chemistry Department and continued to build a major opus on the synthesis, stereochemistry and physicalorganic chemistry of steroids during the following eight years. These interests were continued for a further 13 years at the University of Sydney until his formal retirement in 1969. After a period of five years at Texas Technological University, he returned to Australia and maintained his commitment to science until the end, still working at the bench in his 87th year.

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EARLY YEARS
Charles Shoppee was born on 4 February 1904, at Crouch End (a northern suburb of London), the elder son of Joseph William and Emma Elizabeth Shoppee (ne Hawkswell of York). Charless younger brother, Stanley Shoppee (later FCA), predeceased him in 1967. The family was descended from the noble French family of Chappuis, and could trace its ancestry back to 1109. The male members of the family were generally pillars of the Church or lawyers often Clerk of the Parlement at Lyon, although Louis Chappuis was created Marquis de Mirebel by letters patent of Louis XV of France in 1746. An earlier, female member of the family was distinguished by her descendants, being the great-grandmother of Armand Jean du Plessis, Cardinal Duc de Richelieu, and the great-great-grandmother of the Duc de Villars, Marshal of France. Although Joseph Shoppee was only four years old when his own father died, he nevertheless went on to Kings College, London, where he won several prizes. However, after two years financial circumstances caused him to enter the office of John K. Gilliat and Company of 7 Crosby Square, London. There he remained for the rest of his life (d. 15 August 1944), eventually becoming secretary to the company. Joseph Shoppee was a man of varied intellectual attainments; readily reading French and German, he rapidly learnt Spanish when his company entered the Costa Rica coffee market. Although he had not looked at conic sections and trigonometry for some 35 years, he still knew these subjects well when Charles encountered them. The father was interested in French, German and Italian medieval history, and was well acquainted with medieval architecturehe had visited every cathedral in England and Wales several times. As a species of counterweight to this medievalism, he was also interested in the topography of the railways of England, Scotland and Wales. Thus, Charles grew up in a stimulating environment. At the age of 10 years, Charles went to the Stationers Companys School, where he flourished. He eventually became captain of football, captain of cricket, sergeant-major of the Officer Training Corps, school organist, head prefect, and captain of the school. At about the age of 13, he showed promising talent as a pianist and could struggle (his words) through the Scherzo in B flat minor (op. 31) of Chopin. He studied with Dr R. Walker Robson, acquired the Matthey technique, and gradually became acquainted with some of the works of Bach, Mozart, Beethoven, Chopin, Schumann, Liszt, Brahms, Csar Franck, Scriabin and Rachmaninov. At school, he was greatly influenced by two of the masters, A.E. Richards BA (Cantab.) (Mathematics) and F.T. Addyman, BSc (Lond.), FRIC (Chemistry), eventually passing the Intermediate Examination of the University of London with honours in 1921. On leaving school in 1921, Oxford or Cambridge being financially impossible, Shoppee went to Imperial College (Royal College of Science), where he obtained the ARCS in 1923 and majored in chemistry with first-class honours. In his year were H.J. Emeleus and R.P. (later Sir Reginald) Linstead, both later to be elected to the Fellowship of The Royal Society (in 1946 and 1940, respectively), as was Charles. During the year 192324, he became a research student of Sir Jocelyn Thorpes, and tried to repeat some work on citraconic anhydride said to yield a cyclobutane compound. In fact, the main product, derived by three-carbon tautomerism from itaconic anhydride, was a derivative of cyclopentane. During his years at college, Charles played association football (soccer) for the Royal College of Science and Imperial College, and cricket for the Highgate Cricket Club. He also managed to continue playing the piano and the organ, and even managed to earn some useful pocket money by taking services when the church organist was absent on his summer holiday.

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EARLY CAREER
In 1924 Christopher (later Sir Christopher) Ingold FRS was elected to the Chair of Organic Chemistry at the University of Leeds and invited Shoppee to accompany him, obtaining for him a Department of Scientific and Industrial Research grant of 120 a year. Charless mother had been, before her marriage, a teacher at a school in Kirkstall, near Leeds, and he had distant relatives in Wharfedale who were tenant farmers of Lord Harwood. They lived in a delightful old farmhouse, dating from 1577, called The Nunnery at Arthington. He often used to walk to or from Arthington on Sundays and get a good lunch. At Leeds with Ingold, Charles continued the work, begun with Thorpe, on tautomerism and reaction mechanism, but he never became involved in the IngoldRobinson controversy on aromatic nitration. He played soccer for the University of Leeds and in 1926 his team won the Christie Cup in competition with the universities of Manchester and Liverpool for the first time in 15 years; he was elected captain in 1928. He played twice for the combined Northern Universities XI before the International Selection Committee, but to his disappointment he never secured an England cap. Leeds was an excellent centre for music and he had the good fortune to hear performances by Rosenthal, Hoffmann, Backhaus, Rubinstein, Moiseiwitch, Brailowsky, Cortot, Solomon, Smeterlin, Rachmaninov, Curzon and Paderewski (who at the time was Prime Minister of Poland). In 1926 he was awarded a Senior Research Studentship of the Royal Commission for the Exhibition of 1851 and for a variety of reasons decided to hold the award at Leeds instead of going to Europe. In the summer of 1929 he became a demonstrator in organic chemistry at Leeds, and on the strength of this appointment he married Eileen West on 18 July 1929. Eileen was later found to be a distant cousin of Margery Bell (ne West), the wife of the eminent physical chemist R.P. Bell (FRS 1944). Eileen Shoppee was from Leeds and was in her youth a fine tennis playerof Yorkshire County standingwhile Charles himself was still playing competitive tennis in the Langland tournament in Swansea two decades later. In 1930, Ingold left Leeds for University College London, and Shoppee and several other students were left (in their words) high and dry in the provinces. He obtained his DSc (London) in 1931, and was promoted to Assistant Lecturer in 1936. He made several attempts to move from Leeds during the period 193138, but junior academic posts were in short supply after the financial crisis of 1930 and the subsequent Depression. On a visit to the University of Manchester, he had the good fortune to meet I.M. (later Sir Ian) Heilbron, FRS, and told him that he was stranded in Leeds. On Heilbrons advice, he persuaded the University of Leeds to nominate him for a Rockefeller Research Fellowship in 1938. In the spring of 1939, on the very same day, he received two letters: one offering him a Leverhulme Research Fellowship at the University of Oxford for two years, the other offering him a Rockefeller Research Fellowship for one year at any university that he cared to select. Eventually he decided, with some heartache, to accept the Rockefeller invitation, and then there arose the question of where to go. He decided against Harvard or Yale as perhaps being too much like England, and was tempted to go to Adolf Butenandt (ForMemRS 1969) at the Kaiser Wilhelm Institut in Berlin, but his wife considered it would be too dangerous. He then thought of going to Leopold Ruzicka (ForMemRS 1942) in Zurich and sought the advice of Heilbron, who pointed out that Ruzicka had a very large research group and that Shoppee would see little or nothing of the great man, whereas Reichstein had left Zurich in 1938 for Basel and had a relatively small research group. So Charles, with his wife and six-year-old daughter, proceeded

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to Basel. The move was to shape his science for the future as he combined his Ingoldian heritage of mechanistic organic chemistry with his freshly acquired skills in steroid chemistry to excellent effect.

BASEL, 193845, AND LONDON, 194548

On 3 September 1939 Charles listened with dismay, but without surprise, to Neville Chamberlains broadcast declaring war on Germany and at once wrote to the ViceChancellor of the University of Leeds offering to resign his Research Fellowship and return home; but he was instructed to continue his work unless he received other instructions from the British Consulate-General in Basel. During the winter of 1939 and the spring of 1940 he worked with Reichstein on the structures of the adrenocortical steroid hormones and completed some of his best experimental work. He acquired Reichsteins micro-technique and learnt how to do column chromatography with colourless, non-fluorescent compounds. At Whitsuntide in 1940, with war news getting worse and worse, the family attempted to return to England, but their French visas never came through and they were compelled to remain in the largest and most beautiful concentration camp in Europe, namely Switzerland, for six years. His contribution to the war effect was accordingly confined to collecting news about Germany and to gathering specimens of petrol from German lorries in Basel and analysing the samples. In 1944, Charles was appointed, in absentia, through the good offices of Sir Ian Heilbron, to a Readership in Chemistry in the University of London, tenable at the Royal Cancer Hospital (now the Royal Marsden Hospital). After a nightmarish journey from Basel to London, taking three days and zigzagging across the Channel in a very small steamer The Isle of Thane, he took up his Readership in May 1945 and the family was able to celebrate VE Day in London. At the Royal Cancer Hospital he worked on the steroid constituents of the unsaponifiable extract of human Bantu livers, but could isolate only cholesterol and its oxidation and dehydration products.

SWANSEA, 194856
In 1948 Shoppee was appointed to the Chair of Chemistry in the University of Wales at the University College, Swansea, succeeding J.E. Coates, a physical chemist. He continued the application of reaction mechanism to the determination of configuration of steroids with some success, and was elected to the Fellowship of The Royal Society in 1956. By present standards, the 1948 Swansea Department of Chemistry would be regarded as far too small a department to give an adequate training in chemistry or opportunities for research. Charles had five members of staff, together with a full-time demonstrator. (Three of the five subsequently became professors, and the demonstrator founded a special chemicals company.) In his eight years in Swansea the department produced about 130 honours graduates in chemistry, and from these a vigorous research school developed. Current orthodoxy suggests that the number of postgraduates would be inadequate for a viable research training, but such a view is hardly tenable, given that the Swansea department produced six professors (R.J.W. Cremlyn, W.O. George, D.H. Richards, M.W. Roberts, J.M. (later Sir John Meurig) Thomas (FRS 1977)

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and W.J. Thomas), as well as a polytechnic director (D.W.F. James) and several university readers and senior lecturers. Shoppee was able to generate enthusiasm among his staff and students. He had a genial, friendly disposition and was ready to ask his most junior colleagues for their advice on research problems. In the teaching of chemistry he had a favourite adage, there are not three chemistries, organic, inorganic and physical, but just onechemistry itself. He consequently supported the research interests of all his colleagues with students and finance for apparatus and expensive chemicals, despite the fact that the departmental funding was generally hard pressed. He was also ready to listen to the beginning research students and to accept their choice of research topic and supervisor, even when this did not coincide with his own inclinations. He was often accompanied by his dog, Wally, and a member of the technical staff would be requested to exercise the dog in the adjacent park. It was not uncommon to see Shoppee returning to his home for lunch as a pillion rider on a motorcycle driven by a member of the technical staff, with the dog occupying an intermediate position.

SYDNEY, 195669
However, the damp climate of Wales affected Eileen Shoppees health and, after she had suffered a long series of upper respiratory tract ailments, Charles was advised by former colleagues in Harley Street to seek a warmer and sunnier climate for her. He therefore accepted an invitation to the Chair of Organic Chemistry at the University of Sydney at the end of 1956, after the resignation of Arthur Birch (FRS 1958), who left Sydney for Manchester. When his emigration to Australia became known, Shoppee was jokingly asked, in view of his stereochemical interests, whether going down-under would entail an inversion of nomenclature. After some pondering he realized that it was the subject of a joke. The Sydney sunshine restored his wifes health and they began to enjoy the beauties of a new and fascinating continent. The early part of Shoppees tenure at Sydney coincided with the relocation of the School of Chemistry from its rather ramshackle accommodation in the Science Road of the University to the modern building in Western Avenue, where it remains to this day. More importantly, his tenure coincided with the period of expansion and flowering of Australian universities, to which he made major contributions. Shoppee continued to apply reaction mechanistic concepts and new techniques to structure determination in natural products, mainly within the context of steroid chemistry, a major part of the work being pursued in collaboration with Associate Professor Ruth E. Lack. Shoppee was elected a Fellow of the Australian Academy of Science in 1958, and served as a member of its Council from 1959 to 1962 and as a Vice President from 1961 to 1962). Although Shoppee never sought administrative positions within the University of Sydney, he was throughout his tenure the head of the Department of Organic Chemistry by virtue of his appointment as professor, and he worked conscientiously and successfully on behalf of his department with the invaluable help of Ern Ritchie FAA, who was to succeed him as Professor of Organic Chemistry in 1969. Shoppee also served a period as Dean of the Faculty of Science (196667) and, although this position was far less central than it is at present, he rendered distinguished service to the Faculty in this capacity. He benefited from the former isolation of Australia that had made sabbatical leave much more accessible than in the UK. Thus, he was able to visit the USA and the UK every two years. These periods of leave proved extremely stimulating, and in 196768 he learnt about the WoodwardHoffman rules, and recognized that some of his early work with Ingold at Leeds

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in 1928 had involved the thermal ground-state cycloaddition of a pentadienyl cation. A paper to this effect appeared in 1969, the year of his retirement, thereby closing the circle on a remarkable career.

POST-RETIREMENT, 197094
He was compulsorily retired at the age of 65 after a year rendered very difficult by the need to become acting head of the School of Chemistry as a consequence of the illness of his senior professorial colleague, R.J.W. Le Fvre FRS, and the subsequent illness and death of his junior professorial colleague, A.E. Alexander FAA. However, associates in the USA had heard that he would be available in 1970, and he was offered the Foundation Welch Professorship of Chemistry at Texas Technological University (Lubbock, Texas), which he took up in January 1970 for a period of five years. He continued some steroid work, but concentrated the main effort of his group on the cycloadditions of penta-1,4-dienyl cations. He retired from the Welch Chair in 1975, and he and his wife returned to Australia to be closer to their daughter, Adrienne Horrigan, her husband, William, and their four grandchildren. After a period as an honorary professorial fellow at Macquarie University (197679) Charles moved to Melbourne to be closer to his family, after the death of his beloved Eileen. He was appointed an honorary visiting professor at La Trobe University in 1980 and maintained his research interests into his middle 80s, working at the bench for one day each week until the age of 87. In his letters he noted that the university encouraged him to waste their money on his chemicals so that he could pursue some long-standing interests.

SCIENTIFIC WORK
Prewar period, 192139

After Shoppee graduated from the University of London, he was invited by Christopher Ingold, the doyen of UK physicalorganic chemists to join him at the University of Leeds, where he had just accepted a chair in chemistry. Ingolds influence on the whole of organic chemistry was enormous and clearly left its mark on Shoppee. Although Shoppee was to devote most of his future research to the chemistry of steroids, the emphasis was very much on mechanism and more physical aspects: among others, he published a series of 70 papers on Steroids and Walden inversion (see below). Late in his career he was to become ever more preoccupied with structure and mechanism. At Leeds he continued the work, begun with Thorpe, on tautomerism and reaction mechanisms until Ingolds return to London. Later, during the period 193138, he extended these studies to various cyclopentenes, publishing a series of papers jointly with Harold Burton. Basel, 193945 Supported by a Rockefeller Research Fellowship, Shoppee decided to join Tadeus Reichsteins group at Basel in the spring of 1939, a fateful decision in several respects. The adrenal glands of mammals comprise two sharply differentiated regions, the medulla producing ( )-adrenaline, and the cortex elaborating several hormones essential to life. Absence of these hormones, after destruction of the glands by tubercular infection (Addisons disease) or bilateral adrena-

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lectomy, was shown to lead to multiple insufficiency symptoms and death. In about 1930, adrenocortical extracts were prepared, which by daily injection were capable of maintaining patients with Addisons disease and adrenalectomized animals alive for practically unlimited periods. It was at first thought that the biological activity of such extracts was due to a single substance, but during the period 193560 47 compounds were isolated. Eight of these compounds are highly active, including cortexone, aldosterone, cortisone and cortisol, this last being the most important adrenocortical hormone. Four groups of workers were engaged in the isolation of individual compounds, 31 of which were discovered by the Reichstein group. Milligram amounts of individual steroids were isolated from half a tonne of adrenal glands that had been obtained from 20 000 cattle. Shoppee discovered that the inert 11-oxygen function, characteristic of the adrenocorticoids, could be smoothly removed as an axial 11 hydroxyl group by acid-catalysed dehydration. Subsequent conversion into known steroids provided the first direct structural correlation for these compounds. Reichstein and Shoppee also worked on the structures of cardiotonic glycosides and their aglycones. Certain steroidal glycosides isolated from plants possess powerful cardiotonic activity. Acidic or enzymatic hydrolysis affords the steroid aglycones or genins. The cardiotonic property is associated with the special structure of the aglycone but is modified in regard to solubility and transport by the nature of the conjugated sugars. Use of digitalis in heart therapy was introduced in 1785 by the Scottish physician William Withering and met with spectacular success. Administration in cases of impaired heart function leads to decreased rate and increased intensity of the heart beat, whereas overdosage produces systolic stoppage of the heart. In addition to use in cardiotherapy, some glycosides have been used as drugs in trials by ordeal and as arrow poisons. The free aglycones are convulsive poisons rather than heart stimulants and are of little medicinal value. The main sources of the glycosides are plants of the Apoeynaceae, Liliaceae, Ranunculaceae and Scrophulariaceae; certain species of Digitalis (foxglove) furnish most of the drugs of therapeutic value. Shoppee and Reichstein worked on the structure of diginin, isolated from leaves of Digitalis purpurea by Karrer in 1936, which was actually devoid of cardiac activity; 13 g of glycoside was supplied by Hoffmann LaRoche. By a series of transformations, including WolffKishner reduction and hydrogenation, Shoppee was able to degrade the derived aglycone, diginigenin, to the parent hydrocarbon, which was not identical with any hydrocarbon known at the time, and arrived at the tentative formula 1. An intermediate diketone was later identified by Press and Reichstein by synthesis as 5 ,14 ,17 -pregnane-3,20-dione. This evidence established the steroid nature of diginigenin and the location of oxygen functions at C-3 and C-20. However, it was another two decades before Shoppee, in collaboration with Ruth Lack and Alex Robertson at the University of Sydney, established the correct structure as 2 with the benefit of NMR data. In 1943, with Reichsteins approval, Shoppee started to apply reaction mechanistic concepts to the reactions of natural products, and particularly O O H H HO
(1)

H O O H H HO
(2)

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a Yb c

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a X Y c Figure 1 b + X-

1 2 5

6 Figure 2

steroids, with which he was in the vanguard of a huge and widespread activity prompted in part by the pharmaceutical industrys interests in these important compounds. Postwar period, 194548 In May, 1945 Shoppee took up a Readership in Chemistry in the University of London and was based at the Royal Cancer Hospital. While there, he initiated his remarkable series of 70 papers on Steroids and the Walden inversion, the latter term describing a process (which would now be labelled as SN2 substitutionsee figure 1) in which a group attached to an organic molecule is replaced by another group with inversion of the configuration of the carbon atom bearing the leaving group. In practice, the title of the series was a convenient label for wide-ranging explorations of structure, stereochemistry and mechanism. Ironically, much of the chemistry described in the very first paper involved the retention of configuration rather than inversion. At the time there was considerable controversy over the conformation (shape) of the six-membered cyclohexane ring and compounds containing this structure. Two major conformations are possible (figure 2). One is a rigid puckered shape described as a chair in which carbons 2,3 and 5,6 are coplanar, with C-1 above this plane and C-4 below. The second conformation is quite mobile and has C-1 and C-4 both above the plane; it is described as a boat. Shoppee calculated that the barrier between the two conformations should be ca. 10 kcal mmol 1, a remarkably close estimate to the now established value of 11 kcal mmol 1. D.H.R. (later Sir Derek) Barton (FRS 1954), with whom Shoppee later published a brief communication on the conformation of cyclohexene, received the Nobel Prize for his research in this area. Swansea, 194856 Shoppee was invited to the Chair of Chemistry in this small but vigorous department. However, as in much of the UK, not much research had been done during the war and its aftermath. He set about building it up and was to enhance its standing considerably. He continued his research on steroids, a significant part of it in collaboration with G.H.R. Summers, publishing prolifically on transformations applied to various parts of these molecules. In addition to continuing the Walden inversion series, he also began in 1952 a new series of (ultimately) 39 papers on broader aspects of steroid chemistry. One special interest was the behaviour of 5-3 -hydroxy steroids (a major feature of cholesterol). From his

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H H
ArSO2O 3
5 XFigure 3

H H H X H

earlier work at Leeds with Ingold, Shoppee recognized that in substitution reactions at C-3, the 5-ene bond was participating in the reaction (partial bonding between C-3 and C-5) so that retention rather than the more normal inversion prevailed. Under the right conditions, a bond is actually formed between C-3 and C-5 with the addition of a ligand to C-6 to form an i-steroid (figure 3). Again, we should note that although such changes would be obvious with the benefit of modern spectroscopic techniques, it was a triumph of analytical reasoning to deduce such changes in their absence. And although the results from these and other studies pursued by Shoppee and his co-workers were of vital importance to our knowledge of steroid chemistry, they also informed wider areas of endeavour in our understanding of modern organic chemistry. During this period, he published more than 65 articles and original papers, the value of which was recognized in 1956 by his election to the Fellowship of The Royal Society. University of Sydney, 195669 Arriving in Sydney must have been a terrible shock for Shoppee. It was before the Murray Report in 1957 that was to revolutionize the funding and organization of Australian universities under Commonwealth auspices (with enormous resistance from the individual states). Research funding and modern equipment for organic chemists were almost non-existent; there was not even an infrared spectrometer in the Organic Chemistry Department, and it was necessary to plot ultraviolet spectra by hand. Shoppees predecessor, Arthur Birch, had departed for a chair at Manchester in sheer frustration, prompting newspaper headlines referring to Beggars in mortarboards. David Craig (FRS 1968) and Ronald (later Sir Ronald) Nyholm (FRS 1958) left soon afterwards, reinforcing the message, although Birch and Craig were to return in 1967 to found the Research School of Chemistry at the Australian National University. Nyholm participated in the planning, but elected to remain in the UK. Nevertheless, Shoppees research on steroids prospered. He continued his interests in the bromination of steroidal ketones, but branched out to modification of various steroidal skeletons and the insertion of nitrogen into various rings in a search for interesting biological activity. His research was given a considerable boost with the arrival of modern spectrometric methods (for organic chemists) and he enthusiastically embraced these new techniques, especially nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (in addition to ultraviolet and infrared spectroscopy, which had finally been established at Sydney). The techniques were liberating and, among other objectives, Shoppee revisited long-standing problems, finally deriving definitive structures for several steroidal sapogenins, including diginigenin (see above), digifologenin and digacetigenin. With the publication of the WoodwardHoffman rules in 1964, the principles underlying huge tracts of hitherto poorly

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understood organic mechanisms were revealed. For Shoppee it was intoxicating, and he revisited the research that had been undertaken with Ingold and then Burton, finally achieving a full understanding of the processes involved. Texas Technological University, 197074 After his retirement from Sydney University, Shoppee moved to a chair at Texas Tech, where he continued his interests in electrocyclic processes, publishing a dozen or so papers in this area. He was especially interested in re-examining the thermal ground-state [ 2s+ 2a] conrotatory cycloadditions of penta-1,4-dienyl cations, the photochemical excited-state [ 2s+ 2s+ 2s] disrotatory cycloaddition of a penta-1,4-dienide anion, and some photochemical excited-state [ 2s+ 2s] or [ 2a+ 2a] disrotatory cycloadditions of penta-1,4diene molecules. Retirement years, 197594 Shoppee returned to Australia in August 1975 and took up an appointment as an honorary professorial fellow at Macquarie University (197679), then moved to Melbourne to be closer to family after the death of his wife. Shoppee was appointed an honorary visiting professor at La Trobe University in 1980 and maintained a vigorous interest in chemistry until his death on 20 October 1994, aged 90. As a measure of his fascination with chemistry, he was still working at the bench at the age of 87.

CONCLUSION
We should place Shoppees scientific achievements into context. Contemporary organic chemists enjoy the enormous benefits of spectroscopic techniques and separation methods that became available only towards the end of Shoppees career. Without these aids most modern practitioners would not know where to begin, and yet it was a field in which he excelled, especially the assignment of stereochemistry. Problems that could now be solved in a few minutes by a first-year undergraduate, using NMR spectroscopy, would have taken Shoppee and his colleagues several months or even longer. The availability of reagents was extremely limited and very few were commercially available. From a modern perspective it is difficult to understand how it was possible to isolate and deduce the structures of organic molecules, especially those as complex as the adrenocortical steroid hormones, before the availability of NMR spectroscopy in the late 1950s. And yet chemical and some limited physical methods were sufficient for Shoppee and his co-workers until the arrival of the first NMR spectrometer (a Varian A60) at Sydney in 1962. The advent was almost too late for Shoppee, but it was a turning point for those of us that followed. In 1998, the University of Wales at Swansea launched the C.W. Shoppee Memorial Appeal to fund scholarships for entering chemistry students. Students from all over the world are eligible, reflecting the international nature of the career pursued by Shoppee,

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ACKNOWLEDGEMENTS
I am most grateful to William Horrigan, the late Sir Ewart Jones FRS, Brian Gowenlock, John Davies and R.H. Davies for providing material relating to the earlier stages of Shoppees career, and to Sever Sternhell and Henry Shine for information on the later years. The frontispiece photograph is reproduced by courtesy of the Victoria and Albert Museum. Copyright Victoria and Albert Museum Archives.

BIBLIOGRAPHY
A full bibliography appears on the accompanying microfiche. A photocopy is available from The Royal Societys Library at cost.

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