Sir Alan Rushton Battersby FRS (4 March 1925 – 10 February 2018) was an English organic chemist best known for his work to define the chemical intermediates in the biosynthetic pathway to vitamin B12 and the reaction mechanisms of the enzymes involved. His research group was also notable for its synthesis of radiolabelled precursors to study alkaloid biosynthesis and the stereochemistry of enzymic reactions. He won numerous awards including the Royal Medal in 1984 and the Copley Medal in 2000. He was knighted in the 1992 New Year Honours. Battersby died in February 2018 at the age of 92.
Battersby in his office
Alan Rushton Battersby
4 March 1925
|Died||10 February 2018 (aged 92)|
|Alma mater||University of Manchester|
University of St Andrews
|Spouse(s)||Margaret Ruth née Hart|
|Awards||Davy Medal (1977)|
Paul Karrer Gold Medal (1977)
Royal Medal (1984)
Tetrahedron Prize (1995)
Copley Medal (2000)
|Institutions||University of St Andrews|
University of Illinois
University of Bristol
University of Liverpool
|Thesis||Researches into the structure of Emetine (1949)|
|Doctoral advisor||Dr Hal T Openshaw|
|Doctoral students||Andrew D. Hamilton|
|Influences||Alexander R. Todd|
Alan Battersby was born in Leigh, Lancashire, on 4 March 1925, one of three children of William Battersby, a builder, and his wife Hilda. At the age of 11 he entered Leigh Grammar School, where his chemistry teacher, Mr Evans, nurtured and encouraged him. He would have continued his schooling into the sixth form but for the fact that by age sixteen the Second World War was underway and he decided that he should join the war effort by working for BICC in their local factory. He soon concluded that this decision had been a mistake and so used his spare time to study independently for the Higher School Certificate that would be required to enter university. In October 1943, Alan Battersby took up his place at the University of Manchester's Chemistry Department, having won a scholarship to support his undergraduate studies. He graduated with first class honours in 1946 and that year obtained a Mercer Chemistry Research Scholarship (named in honour of John Mercer) and a DSIR grant. These awards allowed him to complete an MSc (Manchester) in 1947 under the supervision of Dr Hal T Openshaw. When Openshaw was appointed as a Reader at the University of St Andrews, they both moved there and Alan Battersby completed his PhD, which was awarded in 1949. He was immediately appointed an assistant lecturer at St Andrews. This first appointment extended from 1949 to 1953 but was interrupted by two years owing to a Commonwealth Fund Fellowship he obtained for post-doctoral study in the United States. The first year was spent with Lyman C. Craig at the Rockefeller Institute for Medical Research, New York, working on the peptide antibiotics tyrocidine and gramicidin S. The second year involved a move to the biochemistry department of the University of Illinois, working with Herbert Carter on pyruvate oxidation factor.[a]
In 1954, Alan Battersby was appointed a lecturer at the University of Bristol, where he stayed until 1962. This was the period when his own research group of doctoral and post-doctoral students became established. In 1962 he was appointed as a professor of chemistry at Liverpool University until, in 1969, he moved to a professorship at the University of Cambridge and became a Fellow of St Catharine's College. At the time, this was the second Chair of Organic Chemistry at the University, created especially for him; Lord Todd then held the first. In 1988, Professor Battersby was elected to the prestigious 1702 Chair of Chemistry in his department and held that post until his retirement in 1992 when he was granted emeritus status within his college and department, reflecting his distinguished service.
The full output of Sir Alan's work has been published in over 350, mainly peer-reviewed, articles. His research, particularly at Cambridge, took a very collaborative approach which was necessary given the extended time period of the ambitious projects undertaken. Aside from his postgraduate and post-doctoral students, who participated typically for one to three years, the Battersby group included other members of the academic staff of the department, notably Jim Staunton, Ted McDonald and Finian Leeper. The group was funded by external grants, including those from the SERC, the EPSRC, the Leverhulme Trust, Hoffman-La Roche, the Wolfson Foundation and Zeneca.
Alkaloids are a group of naturally occurring chemical compounds that mostly contain basic nitrogen atoms. They have a wide range of pharmacological activities which has made them of considerable interest to researchers. Prior to the 1950s, experimentation, often involving chemical degradation and partial or complete synthesis of possible structures, was necessary to determine their chemical identity which, owing to their stereochemistry, was often difficult to fully describe. This, for example, was the case for emetine, used for the treatment of amoebic infections and the subject of Alan Battersby's PhD thesis. As he later commented
"Roughly 100 g of emetine had been consumed in this work; modern tools would allow the structure of emetine to be determined in three days at most using about 10 mg of recoverable material (365 times faster using 10,000 times less material)."
These tools are the now-familiar mass spectrometry, multi-atom nuclear magnetic resonance spectroscopy and X-ray crystallography: when applied to alkaloids these allowed relationships in structural sub-types to be clarified. This meant that attention could switch to an understanding of the biosynthetic pathways by which these materials are produced in the bacteria, fungi, plants and animals in which they are found. In 1937, Sonderhoff and Thomas showed how deuterium-labelled acetate could be used to investigate the biosynthesis of fats and steroids; by 1950 13C and 14C labelled acetate had been incorporated into cholesterol. Alan Battersby realised that these techniques could be used to study alkaloid biosynthesis and that it was timely to do so because simple one-carbon precursors had become commercially available. By using radiolabelled starting materials incorporating tritium or, especially, 14C to follow intermediates on the pathway, he determined the sequence in which the multiple alkaloids found together in a given organism were formed. For example, the biosynthesis of morphine was shown to proceed from L-tyrosine via reticuline, salutaridine, thebaine, codeinone and codeine. The Battersby group worked on many other alkaloids, for example colchicine, (from the autumn crocus Colchicum autumnale) which is used to treat gout. This was shown to be derived from the amino acids phenylalanine and tyrosine via (S)-autumnaline. Similarly, the biosynthesis of the indole alkaloids ajmalicine, corynantheal, catharanthine and vindoline was shown to involve the precursors tryptamine and loganin. To Alan Battersby's surprise, quinine, the anti-malarial drug was shown to derive from corynantheal, although it does not share its indole substructure.
Alan Battersby is, above all, known for his research on the biosynthesis of the "pigments of life" that are built on closely related tetrapyrrolic structural frameworks. His research group elucidated, in particular, the essential role played by two enzymes, deaminase and cosynthetase, in the steps from aminolevulinic acid via porphobilinogen and hydroxymethylbilane to uroporphyrinogen III. The latter is the first macrocyclic intermediate in the biosynthesis of haem, chlorophyll, vitamin B12, and sirohaem. The work involved the careful study of labelled intermediates, using deuterium, tritium, 13C and 14C placed into potential precursors made by organic or enzyme-assisted synthesis. The most successful strategy was to incorporate the stable isotope 13C into potential substrates, since the outcome of the biochemical reactions (for example giving uroporphyrinogen III) could readily be followed using high-field 13C NMR. The Battersby group's use of doubly-13C-labelled porphobilinogen was especially revealing of the rearrangement step which had puzzled those who wished to understand the details of the biosynthesis of uroporphyrinogen III. Based on these results, Alan Battersby suggested that a spiro-pyrrolenine intermediate was generated at the active site of cosynthetase and to prove this mechanism his group designed and synthesised a spiro-lactam analogue which was indeed shown to inhibit the enzyme.
Later steps towards vitamin B12, especially the incorporation of the additional methyl groups of its structure, were investigated using methyl-labelled S-adenosyl methionine. It was not until a genetically-engineered strain of Pseudomonas denitrificans was used, in which eight of the genes involved in the biosynthesis of the vitamin had been overexpressed, that the complete sequence of methylation and other steps could be determined thus fully establishing all the intermediates in the pathway.   As Alan Battersby wrote in his review article in Accounts of Chemical Research
"One can get some appreciation of the massive effort that was involved by the groups of Arigoni, Battersby, Francis Blanche, Vladimir Bykhovski, Joel Crouzet, Gerhard Muller and A. Ian Scott; K. Bernhauer and David Shemin also made some early contributions."
The Battersby group's work on the biosynthesis of haem-related natural products involved considerable organic synthesis. For example, they produced fully synthetic haem a, haem d1 and sirohydrochlorin. Another challenge requiring pure synthesis was to investigate the function of the enzymes that contained porphyrin-related ligands, or (in the case of haemoglobin) used haem for oxygen-transport, by mimicking these properties without recourse to the protein that in nature surrounds the active site. Alan Battersby chose to investigate mimics for myoglobin and cytochrome P450, designing artificial targets wherein a single metal-containing coordination complex was synthesised and its behaviour compared with the natural system it was replacing. The small-molecule targets were porphyrins carrying substituents in positions where they would be unlikely to interfere with the electronic properties of the metal complex. By the time that he retired in 1992, this area of chemistry had become very active. 
The work described above is a subset of a broader field which attempts to understand the stereochemistry and mechanism of enzyme catalysis. The Battersby group used their expertise in the use of tritium-labelled substrates to probe a number of enzyme systems, for example histidine decarboxylase and tyrosine decarboxylase.
Alan Battersby married Margaret Ruth née Hart in 1949. She was a botanist by profession who died of cancer in 1997. They had two sons, Martin and Stephen, four grandchildren and, after Margaret died, Alan acquired three great-grandchildren. In retirement, he enjoyed hiking and fly-fishing but he also kept in touch with his many colleagues and former students.
Alan Battersby received Honorary Doctorates from his alma mater the University of St Andrews, in 1977, Rockefeller University, the University of Sheffield in 1986, Heriot-Watt University in 1987, Bristol University in 1994  and Liverpool University in 1994. In 1988, he was elected a Foreign Honorary Member of the American Academy of Arts and Sciences, and a Foreign Fellow of the National Academy of Sciences of India in 1990. He was awarded the Wolf Prize in Chemistry along with Duilio Arigoni of ETH Zurich in 1989 for "their fundamental contributions to the elucidation of the mechanism of enzymic reactions and of the biosynthesis of natural products, in particular the pigments of life".
Lord Todd (1944-1971)
Ralph Raphael (1972-1988)
| 1702 Professor of Organic Chemistry, Cambridge University
was a common year starting on Thursday of the Gregorian calendar, the 1925th year of the Common Era (CE) and Anno Domini (AD) designations, the 925th year of the 2nd millennium, the 25th year of the 20th century, and the 6th year of the 1920s decade.2018
was a common year starting on Monday of the Gregorian calendar, the 2018th year of the Common Era (CE) and Anno Domini (AD) designations, the 18th year of the 3rd millennium, the 18th year of the 21st century, and the 9th year of the 2010s decade.
2018 was designated as the third International Year of the Reef by the International Coral Reef Initiative.2018 in science
A number of significant scientific events occurred in 2018.2018 in the United Kingdom
Events from the year 2018 in the United Kingdom.Andrew D. Hamilton
Andrew David Hamilton (born 3 November 1952) is a British chemist and academic who is the 16th and current President of New York University. From 2009 to 2015, he served as the Vice-Chancellor of the University of Oxford. Before leading Oxford, he was Provost of Yale University from 2004 to 2008.Copley Medal
The Copley Medal is an award given by the Royal Society, for "outstanding achievements in research in any branch of science." It alternates between the physical and the biological sciences. Given every year, the medal is the oldest Royal Society medal awarded and the oldest surviving scientific award in the world, having first been given in 1731 to Stephen Gray, for "his new Electrical Experiments: – as an encouragement to him for the readiness he has always shown in obliging the Society with his discoveries and improvements in this part of Natural Knowledge".Craig Hawker
Craig J. Hawker (born January 11, 1964) is an Australian-born chemist. His research has focused on the interface between organic and polymer chemistry with emphasis on the design, synthesis, and application of well-defined macromolecular structures in biotechnology, microelectronics and surface science. Hawker holds more than 45 U.S. patents and has co-authored over 300 papers in the areas of nanotechnology, materials science and chemistry. He was listed as one of the Top 100 most cited chemists worldwide over the decade 1992–2002. and again in 2000-2010. Hawker is currently the director of the California Nanosystems Institute and holds a number of other laboratory directorships at the University of California, Santa Barbara.Department of Chemistry, University of Cambridge
The Department of Chemistry at the University of Cambridge is the chemistry department of the University of Cambridge. It was formed from a merger in the early 1980s of two separate departments that had moved into the Lensfield Road building decades earlier: the Department of Physical Chemistry (originally led by Professor Ronald Norrish FRS, Nobel Laureate; the department was previously located near the Old Cavendish in Free School Lane - see photo) and the Department of Chemistry (that included theoretical chemistry and which was led by Lord Alexander R. Todd FRS, Nobel Laureate) respectively. Research interests in the department cover a broad of chemistry ranging from molecular biology to geophysics. The department is located on the Lensfield Road, next to the Panton Arms on the South side of Cambridge. As of 2015 the department is home to around 200 postdoctoral research staff, over 250 postgraduate students, around sixty academic staff.Duilio Arigoni
Duilio Arigoni (born December 6, 1928) is a Swiss chemist and Emeritus Professor at ETH Zurich. He has worked on the biosynthetic pathways of many organic natural substances.Electrophilic aromatic directing groups
In an electrophilic aromatic substitution reaction, existing substituent groups on the aromatic ring influence the overall reaction rate or the have a directing effect on positional isomer of the products that are formed. An electron donating group (EDG) or electron releasing group (ERG) is an atom or functional group that donates some of its electron density into a conjugated π system via resonance (mesomerism) or inductive effects (or induction)—called +M or +I effects, respectively—thus making the π system more nucleophilic. As a result of these electronic effects, an aromatic ring to which such a group is attached is more likely to participate in electrophilic substitution reaction. EDGs are therefore often known as activating groups, though steric effects can interfere with the reaction.
An electron withdrawing group ('EWG) (–I or –M effects, for inductive and resonance withdrawal, respectively) will have the opposite effect on the nucleophilicity of the ring. The EDG removes electron density from a π system, making it less reactive in this type of reaction, and therefore called deactivating groups.
EDGs and EWGs also determine the positions (relative to themselves) on the aromatic ring where substitution reactions are most likely to take place; this property is therefore important in processes of organic synthesis.
Electron donating groups are generally ortho/para directors for electrophilic aromatic substitutions, while electron withdrawing groups are generally meta directors with the exception of the halogens which are also ortho/para directors as they have lone pairs of electrons that are shared with the aromatic ring.Leigh, Greater Manchester
Leigh is a town in the Metropolitan Borough of Wigan, Greater Manchester, England, 7.7 miles (12 km) southeast of Wigan and 9.5 miles (15.3 km) west of Manchester, on low-lying land northwest of Chat Moss.
Historically part of Lancashire, Leigh was originally the centre of a large ecclesiastical parish covering six vills or townships. When the three townships of Pennington, Westleigh and Bedford merged in 1875 forming the Leigh Local Board District, Leigh became the official name for the town although it had been applied to the area of Pennington and Westleigh around the parish church for many centuries.
The town became an urban district in 1894 when part of Atherton was added. In 1899 Leigh became a municipal borough. The first town hall was built in King Street and replaced by the present building in 1907.
Originally an agricultural area noted for dairy farming, domestic spinning and weaving led to a considerable silk and, in the 20th century, cotton industry. Leigh also exploited the underlying coal measures particularly after the town was connected to the canals and railways. Leigh had an important engineering base. The legacy of Leigh's industrial past can be seen in the remaining red brick mills – some of which are listed buildings – although it is now a mainly residential town, with Edwardian and Victorian terraced housing packed around the town centre. Leigh's present-day economy is based largely on the retail sector.Lew Mander
Lewis Norman Mander, , FAA, FRS (b. 8 September 1939) is a New Zealand-born Australian organic chemist. He has widely explored the synthesis and chemistry of the gibberellin class of diterpenes over a 20-year period at the Australian National University (ANU). In particular, he studied the effect of these hormones on stem growth and on the reasons why plant undergo bolting during plant development. The July 2004 edition of the Australian Journal of Chemistry was dedicated to Mander on the occasion of his 65th birthday. He retired in 2002 but remained active at the ANU until 2014. In 2018 Mander was made a Companion in the General Division in the Order of Australia which "...is awarded for eminent achievement and merit of the highest degree in service to Australia or humanity at large".
In an interview he gave after winning his award, Mander said that his goal was to improve the efficiency of extracting food from plants with the possibility of reducing food shortages in the future.March 4
March 4 is the 63rd day of the year (64th in leap years) in the Gregorian calendar. 302 days remain until the end of the year.Paul Karrer Gold Medal
The Paul Karrer Gold Medal and Lecture is awarded annually or biennially by the University of Zurich to an outstanding researcher in the field of chemistry. It was established in 1959 by a group of leading companies, including CIBA AG, J.R. Geigy, F. Hoffmann-La Roche & Co. AG, Sandoz AG, Société des Produits Nestlé AG and Dr. A. Wander AG, to honour the Swiss organic chemist and Nobel laureate Paul Karrer on his 70th birthday. The Medal was created by Swiss sculptor Hermann Hubacher; the obverse depicts a relief of Paul Karrer and the reverse is engraved with the words University of Zurich - Paul Karrer Lecture. The lecture itself is delivered at the University of Zurich.
The recipients to date (2015) have represented most of the important research institutions of Europe and the USA and include nine Nobel Prize winners for chemistry or medicine.Steven Zimmerman
Professor Steven C. Zimmerman is an organic chemist on the faculty of the Department of Chemistry, University of Illinois at Urbana-Champaign.Tetrahedron Prize
The Tetrahedron Prize for Creativity in Organic Chemistry or Bioorganic and Medicinal Chemistry is awarded annually by Elsevier, the publisher of Tetrahedron Publications. It was established in 1980 and named in honour of the founding co-chairmen of these publications, Professor Sir Robert Robinson and Professor Robert Burns Woodward. The prize consists of a gold medal, a certificate, and a monetary award of US $15,000.Welch Award in Chemistry
The Welch Award in Chemistry is awarded annually by the Robert A. Welch Foundation to encourage and recognise basic chemical research for the benefit of mankind. The award is named in honor of Robert Alonzo Welch, who made a fortune in oil and minerals and had a strong belief in the ability of chemistry to make the world a better place. The prize has a value of $500,000.Wolf Prize in Chemistry
The Wolf Prize in Chemistry is awarded once a year by the Wolf Foundation in Israel. It is one of the six Wolf Prizes established by the Foundation and awarded since 1978; the others are in Agriculture, Mathematics, Medicine, Physics and Arts.
Laureates of the Wolf Prize in Chemistry
Copley Medallists (1951–2000)