Serge David

1921-2014

David Bonnaffé; Claudine Augé; Jacques Augé; Claire David-Mabille

Serge David was born in 1921 in Grenoble in the heart of the French Alps. His father owned the largest department store in Grenoble, as well as the first motorcar in town. Unfortunately, he died when his son was only 12 years old. Very early on, Serge David developed his skills for what would remain his real passions in life: chemistry (at the age of 8, he was already doing experiments in his small laboratory installed in his parent's cellar); music (which accompanied him throughout his whole life, and he was an accomplished violinist); and mountain climbing (he was still hiking at the age of 91). Without doubt, Music and Mountains nurtured his approach to science by developing his abilities both to explore new frontiers as well as for contemplation. After finishing school in Grenoble, he entered in 1940 the prestigious École Normale Supérieure (ENS), rue d'Ulm, Paris. This was during the war and the time of occupation in France. His days as a student at ENS were rather unusual, not only because he lost his mother, but also because he joined the French Resistance forces in the Alps. Nevertheless, he succeeded brilliantly in his studies, being first-ranked in 1944 for Agrégation in Physical Sciences, one of the most difficult and demanding diplomas in France. He then joined the laboratory of Robert Robinson in Magdalen College, Oxford, where he studied the lipids of the tuberculosis bacillus and defended his Ph.D. in 1947. Back in the ENS in Paris he succeeded, within 15 months and without today's sophisticated techniques of analysis, in elucidating the complete structure of germanicol, a 30-carbon pentacyclic triterpene alcohol. With such a prestigious background, he was appointed in 1948, at the age of only 27, to the post of Lecturer in Biochemistry at the University of Nancy. In 1949, he married Georgette Potier, who became a constant supporter for him in his work, and they had three children (Bruno, Dominique, and Claire). In 1956, he was offered the Chair of Organic Chemistry of the University of Nancy, and in 1963, he moved to the faculty of science of the University of Paris-Sud in Orsay, where he continued to pursue his research and teaching activities. His retirement from teaching responsibilities in 1990 did not signify the end of his involvement in chemistry, since he continued his research as Emeritus Professor until the beginning of the 21th century. One of his major achievements during his as Emeritus career was to write a book "Molecular and Supramolecular Chemistry of Carbohydrates: Chemical Introduction to Glycosciences" (Oxford University Press). Despite its modest title, corresponding well to Serge David's reserved temperament, this book soon became a classic. Even when fully retired he continued to live a rich intellectual life, walking the 5 km between his house in Orsay and the laboratory to access the literature on which he based several original and educational review articles,1-4 the last one being published in 2005 when Serge David was already 84 years old!5

Throughout his career, Serge David showed an outstanding ability to bring together many different resources in chemistry and biochemistry. His brilliant and open mind, fueled by his thirst of learning, allowed him to master a vast base of knowledge, ranging from the most mathematical aspects of molecular orbital theory to metabolic pathways. When facing a challenging problem, he was always able to pose the right question and, by mobilizing the appropriate tools, to address it in an original way6 and pave the way for followers.7 During his career, Serge David published more than 200 articles, not only in carbohydrate chemistry and biochemistry but also in "mainstream" organic chemistry and synthesis. In all of these domains, he made seminal contributions to which his name is now attached. He pioneered in France the use of radioactive tracers for the study of metabolism, which allowed him to decipher the biosynthesis of thiamine,8 determining the origin of all carbon atoms,9 as well as elucidating the biosynthesis of the D-ribose unit of yeast RNA and the deoxyribose component of DNA.10 His interest in carbohydrate chemistry was initially motivated by a need to synthesize specifically labeled monosaccharides, but his scientific curiosity soon led him to embrace all aspects of that discipline. A first major contribution concerned the anomeric effect: using nuclear-quadrupole-resonance measurements,11 he was able to probe the interaction in glycosyl bromides and chlorides between the p-type lone pair on the oxygen atom in the pyranose ring and the adjacent antibonding carbon-halogen orbital, thus providing decisive experimental support to what is nowadays the canonical explanation of the origin of the anomeric effect.12 As an organic chemist, Serge David introduced new methods into carbohydrate chemistry, such as the use of organotin derivatives and the extension of the hetero Diels-Alder reaction in the total synthesis of monosaccharides. His name is now attached to the use of dibutylstannyl oxide to promote regioselective acylation or alkylations in polyols.13 Using X-ray crystallography and 119Sn NMR spectroscopy, Serge David suggested that the dimeric structure of the stannylene intermediate was responsible for the remarkable regioselectivity of this reaction.14 Regarding cycloaddition reactions, by synthesizing and using chiral dienes, he initiated what is apparently the first investigation of chiral induction in cycloadditions.15 He developed this method to build the D-galactose residue at the nonreducing end of the antigenic blood-group determinants and applied it to the synthesis of a half gram of the group A trisaccharide, an incredible achievement at that time.16 In fact, Serge David became interested in the synthesis of oligosaccharides as soon as the structures of the blood-group epitopes had been determined. His work in this area started with the synthesis of a branched pentasaccharide, isolated in minute amounts from mucins of ovarian cysts. Published in 1977, this work was probably the first synthesis of a pentasaccharide. From this work, an extensive program of oligosaccharide synthesis was initiated and further developed in close collaboration with immunologists, especially Ten Feizi from Britain's Harrow Hospital.17 This fruitful collaboration between immunologists and chemists led to the exact structural elucidation of Ii blood-group epitopes through their unequivocal chemical synthesis.18 In the 1980s, Serge David showed great vision by realizing the potential of enzymes in preparative sugar chemistry. He described the use of immobilized sialylaldolase for the preparation of N-acetylneuraminic acid on a 10-g scale,19 a procedure that is now used industrially. In parallel with this work, he succeeded in preparing four glycolipid and two glycoprotein sequences by enzymatic galactosylation of chemically synthesized precursors.20 The door was thus opened for the enzymatic synthesis of oligosaccharides as a valuable alternative to the purely chemical route.21 The appended short bibliography selects some key papers and articles from Serge David's published work.

Serge David was a quiet and reserved person, but all who knew him will miss his sense of humor, his great subtlety, his huge cultural knowledge, and his unique ability to cite or formulate chemical aphorism such as "Equilibrium is death" or "Without activation energy the universe would be only dust". statements that sometimes puzzled his coworkers and distressed first-year students. In 2013, his last visits to the laboratory were, as usual, occasions for intense discussions on the nature of the chemical bond and ongoing projects in the laboratory that he has founded in Orsay 50 years earlier and for which he still maintained a keen interest. None of the three children of Georgette and Serge David became chemists, although Dominique had an academic career as a physicist and mathematician. However, Serge was the Ph.D. mentor of many outstanding chemists (including Pierre Sinaÿ, André Lubineau, Claudine Augé, Jacques Augé, Michel Thérisod, Christine Le Narvor, Alain Veyrières, Jacques Eustache, and Jean-Michel Vatèle), and he bequeathed an extensive network of scholars in the chemical community. His scientific children and grandchildren will miss him, but, most importantly, will remember him for challenging their minds to his example, in formulating clear concepts settled on the basis of rigorous experimental data.

In April 1992, a special issue of the journal Carbohydrate Research was dedicated to Serge David in honor of his 70th birthday; it featured 27 articles from colleagues and friends from around the word.

Testimony to the influence of Serge David in the field of glycosciences at the international level comes from the kind words sent by many colleagues, not only from different countries but also from successive generations. Some of these are noted here.

 Serge will be remembered for his seminal contributions but also his gentle nature. He was very patient with me as a student when we had exchanges on the nature and origin of the anomeric effect. He will be missed but not forgotten (Prof. B. Mario Pinto, Simon Fraser University,...