PRELOG, VLADIMIR

(b. Sarajevo, Austria [later Bosnia], 23 July 1906; d. Zürich, Switzerland, 7 January 1998), chemistry, stereochemistry, structure of natural products.

Prelog is rightly considered the premier stereochemist of the second half of the twentieth century. In 1975 he received the Nobel Prize in Chemistry “for his work on the stereochemistry of organic molecules and reactions.” The word stereochemistry is derived from the Greek στ ρóσ (stereos) meaning “solid” and refers to the three-dimensional chemical properties of molecules. While the perception of the three-dimensional aspect goes back to Louis Pasteur (1848), and the concept of a tetrahedral carbon atom to Joseph Achille Le Bel and Jacobus Henricus van't Hoff (1874), even in the early twentieth century molecules were still commonly depicted as if they were planar. Such representations conceal important aspects of the mutual interaction of molecules, such as that of a drug with its biological receptor or that of an enzyme with its substrate.

Stereochemistry, among other aspects, conveys the concept of handedness (called chirality on the molecular scale): a right glove fits a right hand whereas its mirror

image (a left glove) does not. In an analogous way, a molecule of a given handedness may be effective as a drug, but its mirror image may not (Figure 1 A, B). This principle of fit or misfit plays an important role in chemistry.

Early History In 1906 Prelog’s birthplace, Sarajevo, was the capital of Bosnia-Herzegovina, a province of the Austro-Hungarian empire which later became part of Yugoslavia and was an independent country after 1992.

The region has a long history of ethnic, religious, and political strife. In June 1914, when the Austrian crown prince, Archduke Franz Ferdinand, and his wife visited Sarajevo, young Prelog was delegated to strew flowers in front of their carriage. Just after the procession had passed him, he heard the fatal shots that killed the crown prince and his wife and ushered in World War I. The assassin was a Serbian student, and violent demonstrations against the Serbian minority in Bosnia ensued, resulting in the burning and looting of Serbian-owned shops. This incident left Prelog with a life-long aversion to all violent mass demonstrations, even if undertaken for just causes.

Prelog’s Croatian parents, Milan and Mara (née Costello) separated in 1915 and Vladimir moved in with his paternal aunt in Zagreb, the capital of Croatia, where he completed three years of high school (Realgymnasium). At the age of twelve he had already started some chemical experiments with supplies and equipment he bought, and resolved to become a chemist. In 1918 he rejoined his father in Osijek, Croatia, where his interest in chemistry was encouraged by a good high school teacher, Ivan Kuria, who supervised the writing of Prelog’s first scientific paper (1921). That year he moved back to Zagreb, and upon graduating from high school (1924) he enrolled in a chemical engineering curriculum at the Czech Institute of Technology in Prague.

In his study of organic chemistry Prelog encountered Rudolf Lukes, an enthusiastic young assistant professor, who engaged him as his research assistant. Lukeš worked on alkaloids, and taught Prelog both the theoretical and practical aspects of organic chemistry. Prelog spent most of his undergraduate days doing research and finished his diploma with distinction in three years. Subsequent doctoral studies with Emil Votoçek, the professor of organic chemistry, involved the aglycone of the newly discovered glycoside rhamnoconvolvuline. Within a year Prelog found the compound to be 3,12-dihydroxypalmitic acid and obtained his doctoral degree in 1929.

Chemical Research in Prague and Zagreb Jobs were scarce in 1929 and Prelog was fortunate to meet a school-mate of Lukes, Gothard J. Dríza, a young entrepreneur who was setting up a laboratory for the preparation of fine chemicals and simultaneously wanted to carry out a doctoral project. Dríza offered Prelog the job of assisting in the laboratory, with the opportunity to do some research of his own and the additional duty of supervising Dríza’s PhD work (officially under Votocek). Prelog chose the antimalarial alkaloid quinine for his study, a subject he continued to pursue later in Zagreb and in Zürich. In 1932 he spent nine difficult months in the Royal Yugoslav Navy. On his return to Prague in 1933, he married Kamila Vítek, whom he had met six years earlier. Their son Jan was born in 1949.

In 1933 Prelog became a candidate for the chair of organic chemistry at the University of Zagreb, but, after long negotiation, he was offered instead an appointment (in 1935) as a docent (a poorly paid instructor with large teaching duties). Moreover, the Zagreb laboratory was not equipped for organic synthesis and the budget was insufficient for supplies and the support of coworkers and technicians.

Fortunately, Prelog was again able to make contact with a small but prospering commercial pharmaceutical enterprise, Kaštel, Ltd. (later Pliva). Eugen Ladany, an owner of the firm, decided to expand its scope from fabrication of pills, tablets, and injectables to the manufacture of medicinal products not available locally. Prelog accepted a consultancy with the firm, which involved his devoting part of his university work to the synthesis of pharmaceuticals, in return for support of his laboratory and a personal stipend. Thus one of Prelog’s first doctoral students devised an inexpensive synthesis of the just-discovered antibacterial drug sulfanilamide. This led to financial success for both the company and Prelog and his laboratory and enabled him to spend several months in the laboratory of a fellow Croatian, Leopold Ruzicka, at the ETH (Federal Polytechnic Institute) in Zürich, Switzerland.

Back in Zagreb, Prelog tackled two exciting chemical problems: the synthesis of adamantane and the synthesis of quinine and related alkaloids. Adamantane (C₁₀ H₁₆), isolated from Moravian petroleum by Stanislav Landa in 1933 has a melting point of 266 degrees Celsius, unusually high for a compound with only ten carbon atoms. Landa brought a sample to Lukes’s laboratory for advice; Lukes, noting the tetrahedral crystals, immediately suggested (in Prelog’s presence) that the substance had a highly symmetrical tetrahedral molecular architecture (Figure 2). In Zagreb, Prelog proved this structure by a “rational synthesis,” that is, a synthesis in which each step was sufficiently clear to allow the resulting connectivity of the atoms to be inferred unequivocally. In publishing adamantane’s unusual molecular architecture, he gave credit to his teacher Lukeš for his prediction. Prelog also pursued the synthesis of the antimalarial quinine (C₂₀ H₂₄ N₂ O₂, Figure 3, isolated from cinchona bark in the early nineteenth century) with some success (1943), but this project was not complete at the time he left Zagreb and was later finished by others (Woodward and Doering, 1944 and 1945; see also Stork et al., 2001; summarized by Rúveda, 2005; Seeman, 2007).

The atmosphere for work in Zagreb became increasingly unfavorable with the outbreak of World War II (1939) and the occupation of Croatia by the Germans in 1941. Through his earlier stay in Zürich, Prelog was known to Ruzicka, who had given several German and Austrian Jewish refugees positions in his laboratory. But by 1941, most of them, concerned about the safety of Switzerland as a haven, had emigrated to the United States, leaving Ruzicka with few coworkers; thus his eyes fell on Prelog. Fortuitously, Prelog’s work had also come to the attention of Richard Kuhn, who invited him to Heidelberg for a lecture.

With this invitation, Prelog and his wife were able to receive passports. Ruzicka then arranged for them to receive Swiss visas and once in Italy in transit, the Prelogs proceeded to Zürich rather than to Germany. There Prelog became an assistant in Ruzicka’s laboratory; he was promoted to Privatdozent (roughly equivalent to assistant professor) in 1942 and to titular professor in 1945. In

1943 he became a consultant for CIBA, which supported his research and also augmented his stipend.

Zürich: Natural Products The tradition of the ETH laboratory under Ruzicka was elucidation of the structure of natural products. Thus Prelog’s first project involved isolation of pure chemical compounds from pig testes extracts. Two of these products proved to be related to the known class of steroids but had a pronounced musk odor, and one was found to be a sex attractant for pigs. Interestingly, the same compound was later found to occur in truffles, which explains why pigs are expert in finding truffles in the ground! After some further successful work on steroids as well as terpenes, Prelog, independent of Ruzicka now, switched his interest to alkaloids, impelled perhaps by his long-standing interest in quinine.

Prelog’s first structural target (1942) was the steroidal alkaloid solanidine, readily available locally from potato sprouts. The war-imposed scarcity, not only of chemicals but also of current foreign chemical journals, left him the leisure to read and think about prewar publications. In the process he found an error in the strychnine formula of Sir Robert Robinson—the formula that Prelog suggested in 1945 was not correct either but led Robinson to suggest the correct structure, which was confirmed at the same time by Woodward (1947). Another widely cited achievement of this period was the resolution of Tröger’s base (Figure 4) into two mirror-image forms (Figure 1) (1944). Normally 3-coordinated nitrogen, RR'R”N:, where the fourth corner of the tetrahedron is occupied only by non-bonded electrons, does not sustain chirality because of facile nitrogen inversion, but in Tröger’s base the nitrogen atoms are stereochemically locked and the two enantiomers (mirror-image forms) cannot interconvert. This is also one of the early instances where resolution was effected by column chromatography on an optically active support (specially prepared lactose hydrate).

Prelog then returned to his old love, quinine, but switched from its attempted synthesis to the elucidation of its configuration (3-dimensional architecture). Its constitution and connectivity (Figure 3, A) had been determined in 1908. Each of the four starred carbon atoms bears four different attached neighbors (Figure 1), so there are two possible mirror-image arrangements (A, B) for each starred carbon, making possible 2⁴ or 16 configurational isomers in all. In spectacular studies, Prelog’s group determined the configuration of these four carbon atoms in quinine (1944, 1950), thus completing the determination of its molecular structure (Figure 3, B).

By 1945 partly as a result of his work on adamantane, on Tröger’s base, and on the configuration of the cinchona alkaloids, Prelog had developed a profound understanding of stereochemistry, a subject that would engage him for much of the rest of his life. He also continued working on the structures of natural products, but the war-imposed isolation slowed further progress. This situation changed dramatically in 1946. Renowned colleagues from Britain, France, and the United States visited Zürich to find out about work done there during the war. Thus Prelog met such luminaries as Robert Woodward (Harvard), Robert Robinson (Oxford), Derek H. R. Barton (London), and Maurice Janot (Gif-sur-Yvette, France). Some of these meetings gave rise to collaboration on natural products: on corynantheine and cinchonamine with Janot; and on cevine with Woodward, Barton, and Prelog’s local colleague Oskar Jeger. The visitors also came to appreciate Prelog both as a scientist and as a human being. As a chemist, he was original, quick-minded, focused,

well-read and informed, had an excellent memory, and could constructively discuss many scientific problems. As an individual he was personable, cultured, communicative, self-confident without being overbearing, witty, and collaborative (he preferred collaboration to competition).

In 1947 Prelog decided to present the then-new electronic theory of organic reactions in advanced chemistry lectures, which, he writes, led him to an experimental investigation of medium-sized (8 to 11–membered) ring compounds. These compounds were hard to come by. Prelog—simultaneously with his industrial colleague Max Stoll—found a way to obtain them in good yield by a modified acyloin synthesis. He found their properties to deviate substantially from those of analogous smaller or larger ring compounds, which Prelog ascribed to the unusual shape of these rings, which he called their “constellation.” Because of the potential angle strain in a medium-sized ring, atoms some five or six positions apart tend to buckle into the ring and thus get close together. This gives rise to “transannular” interactions, both chemical and physical, of atoms that would otherwise be too far apart to interact, which had several unusual consequences. The initiation of studies of “medium rings” is one of Prelog’s major achievements. At the same time, however, D. H. R. Barton had been studying and interpreting the chemical and physical behavior of 6-membered rings attributable to their chairlike shape, and coined the term conformation to describe their shape. This term has since been generally accepted in place of “constellation.”

In 1950 Prelog occupied the Reilly lectureship at the University of Notre Dame (South Bend, Indiana) over a six-week period. In addition to presenting twelve lectures there, he visited most of the major Midwestern universities, stopping on the way home in the northeastern United States; in all he gave twenty-five talks. Prelog’s visit to Harvard brought him an offer of a tenured professorship. To counter this offer, Ruzicka persuaded the ETH president to create a second full professorship in the Organic Chemistry Institute, something very unusual then in Europe. While attending the 75-year anniversary meeting of the American Chemical Society in 1951, Prelog was offered the research directorship of Hoff-mann–La Roche, but turned it down despite its financial attractiveness—administration was not his métier. He used his stay in the United States to visit several West Coast universities and spent two stimulating months as Falk-Plaut lecturer at Columbia University in New York. By the time he returned to Zürich, chemistry was in a period of rapid change (and increasing cost!), thanks to the development of new instrumentation—infrared and nuclear magnetic resonance spectroscopy, readily accessible x-ray crystallography—that greatly facilitated the heretofore tedious determination of the structure of natural products by degradation.

Figure 5 .Nonactin.

In this area Prelog turned his attention to the structure of microbial metabolites and antibiotics, made notable by the earlier discovery of penicillin by Alexander Fleming. CIBA in Basel was working on such compounds and enlisted Prelog’s help. The first representative, narbomycin, proved to have a large (14-membered) lactone ring, as did several other antibiotics (macrolides) discovered then and since. Degradation of narbomycin (1956) produced a lactone, also obtained by Carl Djerassi—later called, in view of its importance in synthesis, the Prelog-Djerassi lactone. Another interesting macrolide is nonactin, with a 32-membered ring (1962). The molecule has 16 stereogenic (chiral) centers but shows no optical activity, being made up of four subunits, two of which are mirror images of the other two. Thus the combination is superposable with its mirror image (Figure 5). Other interesting antibiotics studied were echinomycin (1959), the iron-containing ferrioxamines, the antitubercular rifamycin, and the boron containing boromycin.

Prelog’s Rule In 1950 Prelog came upon a 1936 review by the British stereochemist Alexander McKenzie concerning the reactions of esters of phenylpyruvic acid and chiral alcohols with Grignard reagents. The chiral alcohol moiety induces chirality in the atrolactic acid obtained after final saponification (Figure 6) but the correlation between the sign of rotation of the resulting acid and the configuration of the chiral alcohol was not clear. Reasoning on the basis of molecular models, Prelog concluded that alcohol A (Figure 6) would give rise to the known (R)-(-)-atrolactic acid and B to the (S)-(+) enantiomer. This hypothesis—now called Prelog’s Rule—agreed with the configuration of those alcohols that had been independently established and allowed predictions for other alcohols of hitherto unknown configuration. This remarkably reliable though empirical rule pointed the way for similar configurational correlations for other types of compounds.

CIP System of Stereochemical Nomenclature Up to 1951, the configuration of chemical compounds had

been denoted based on their two-dimensional projection formulas, but since there are different ways of projecting a three-dimensional molecule onto a plane, the notation was often not unequivocal and hence confusing. In 1951, Robert S. Cahn, editor of the British Journal of the Chemical Society, and Christopher K. Ingold of University College London devised a notation based on the actual (three-dimensional) disposition of a molecule’s chiral center or centers, and specified the array by means of a prefix to the name of the compound. The system works as follows. Order the substituents a, b, c, and d about the chiral center shown in Figure 1 according to their atomic numbers (a > b > c > d, for example, Br > Cl > F > H; the so-called sequence rule) and orient the tetrahedra such that d is in the back. Then if a-b-c represents a clockwise array, the compound is given a descriptor (prefix) now called R (for Latin rectus); for the counterclockwise array the descriptor is S(for Latin sinister).

Prelog tells the story that, in an evening reception at a meeting of the British Chemical Society, he sat together with Cahn and Ingold (then president of the Chemical Society) drinking beer. Prelog vigorously criticized some aspects of the 1951 sequence rule, with the unexpected result that the two Englishmen asked him to join them in further developing their ideas. The eventual result was an improved paper in 1956 and a further extended one in 1966. This CIP (Cahn-Ingold-Prelog) stereochemical nomenclature is now used in hundreds of thousands of scientific papers all over the world. Some additional changes were suggested in 1982 (with G. Helmchen); Prelog also published a system to describe conformation (with W. Klyne, 1960) and a general system to describe the steric course of asymmetric reactions (with Seebach, 1982).

Institute Headship and Later Work Ruzicka retired in 1957 and Prelog became head of the Organic Chemical Institute of the ETH. One of his tasks was to attract and retain top-notch faculty. Prelog realized that his institute already had a number of outstanding Privatdozenten: Edgar Heilbronner, Albert Eschenmoser, Duilio Arigoni, and Wilhelm Simon. He succeeded in gradually obtaining full professorships for all of them, as well as for associate professors Jack Dunitz, Oskar Jeger, and Emil Hardegger. Having more than one full professor in one European institute was still quite unusual in the early 1960s. In 1965 Prelog further decided to adopt the U.S. departmental model: he stepped down as department head and installed a rotating chairmanship, with all full professors participating in important decisions. In the process he created a remarkable collegial spirit in the institute that extended, beyond administration, to scientific interaction and personal friendship. Although most of the faculty members promoted under Prelog became widely recognized and sought after (several became foreign associates of the U.S. National Academy of Sciences); only one of them, Heilbronner, ever left the ETH.

Prelog was now at the peak of his scientific career. In 1960 he was elected to the governing board of the large Swiss pharmaceutical company CIBA. He presented lectures all over the world (at 150 locations, by his estimate), including many named lectureships, such as the Baker lectureship at Cornell University. During this period and in subsequent years he received many honorary degrees (eleven in all, including doctorates from Cambridge, Paris, and the Weizmann Institute) and numerous honorary or foreign memberships in national academies, including the Leopoldina, the Pontifical Academy, the National Academy of Sciences (USA), the (British) Royal Society, and the American Philosophical Society. His many medals and awards (nineteen in all) include the 1969 Roger Adams Award, then the top award in organic chemistry of the American Chemical Society. Perhaps significantly, the last sentence of the nomination for that award (following a description of Prelog’s science) reads: “He has many friends and few enemies.”

As Prelog’s reputation spread in the 1950s, excellent PhD candidates joined his group; several of these later attained professorships at major universities, mainly in German-speaking Europe. He also attracted many postdoctoral fellows and senior visiting chemists from all over the world, especially Prelog’s native Yugoslavia. He was a good academic host, ever ready to talk and interact with his visitors even when they did not work on joint problems with him.

The 1960s saw a renaissance in the understanding of stereochemistry, in part prompted by Prelog’s work in the previous decade. In 1965, Professor Andre Dreiding (at the University of Zürich) organized a EUCHEM Conference on Stereochemistry, which took place in some very elegant hotels on the Bürgenstock, a steep bluff near the southwestern end of Lake Lucerne, and thereafter (it recurs annually) was known as the Bürgenstock Conference. As he explained later (1989), Prelog was at first unenthusiastic—he felt there were already too many meetings and thought the stereochemical viewpoint might be too narrow to sustain yearly conferences. On both points he quickly changed his mind: The conferences gave him an opportunity to discuss many aspects of the field with colleagues (mainly European ones), and it turned out that the stereochemical point of view easily covers many aspects of the increasingly cross-disciplinary chemical sciences. Prelog became a regular attendee at subsequent Bürgenstock conferences.

Although most of Prelog’s research was basic, both his background and his industrial connection kept him in touch with applications, especially in drug development. One of these problems was the synthesis of compounds in enantiomerically pure form, for, as explained earlier, often only one of the two enantiomers of a chiral compound is pharmacologically active. Nature solves this problem with enzymes, which either produce or separate out single enantiomers. Prelog, in the 1950s, initiated a study of such enzymes, isolated from microorganisms, for use in vitro. The reactions chosen were reductions of cyclic ketones to alcohols, and by utilizing a large number of different ketones as well as three different enzymes, his group developed so-called diamond lattice models to depict the active sites of the enzymes by determining which compounds were reduced stereoselectively. The work continued for some fifteen years (1956–1977, including a review, 1964; see also 1976).

Although the enzymes studied were not accessible enough for commercial use, the work provided impetus for later studies by others. A later approach to the separation problem involved chiral ionophores (1975–1986). Ionophores (ion carriers) make salts that are ordinarily water-soluble. When a chiral moiety is part of, or attached to, the ionophore (see e.g. Figure 7), the solubilization may be selective for a single enantiomer and may thus be used for separation of individual enantiomers (resolution). The actual separation may be effected by partition between a fat-soluble and a water-soluble phase by single or countercurrent extraction, by partition chromatography, by transport across fat-soluble membranes, or by migration between enantioselective electrodes.

The Later Years Prelog’s first involvement with nomenclature had been from 1951 to 1954, as a member of the international (IUPAC) Nomenclature Commission. It is there that he first met Robert S. Cahn and interacted with Friedrich Richter and Oskar Weissbach, editors of Beilsteins Handbuch der organischen Chemie, a compendium of all known organic compounds. It was those editors’ acceptance, after extensive trials, of the CIP system for listings of chiral compounds in the Handbuch that secured worldwide acceptance of the system. There were compounds whose chirality was different from that depicted in Figure 1, such as appropriately substituted allenes (abC=C=Cab), spiranes, biphenyls, helical structures, and several other types (such as Tröger’s base, Figure 4) and ad hoc rules had been added to the CIP system (1965, 1982) to include these types. Indeed, a new type of stereoisomerism, cyclostereoisomerism, discovered by Prelog with Hans Gerlach and Yuri Ovchinnikov (1962, 1964), is exemplified in Figure 8: Of the various sequences in which two enantiomeric monomers a and b, can be arranged in a cyclic oligomer (e.g., a cyclic oligopeptide), there are two that differ from each other by having clockwise or counterclockwise arrangements of the a-a-b-a-b-b sequence.

As a result of the diversity of chiral molecules, Prelog began to look for a system (presumably mathematically based) that would cover all such compounds and preferably even predict their existence. His group first synthesized a number of molecules with novel combinations of chiral centers, axes, and planes (1969–1982). All these

molecules proved to be either chiral or achiral, according to prediction. However, the more general conceptual work, carried out in collaboration with Andre Dreiding until Prelog’s death, did not lead to a final conclusion; a fragment of this work has been published in Prelog’s Nobel lecture (1976).

In 1975 Prelog received the Nobel Prize in Chemistry jointly with John W. Cornforth (U.K.). Both prizes were for stereochemistry; Cornforth’s for his ingenious work on biochemical applications, Prelog’s for his leading role in the contemporary development of the subject. The following year Prelog, now seventy, had to retire, there being no emeritus status at the ETH. In order to retain an office and workplace, Prelog became the equivalent of a postdoctoral fellow, formally associated with one of his younger colleagues, and was able to continue his work, mostly with Croatian coworkers whom he paid with personal funds. In 1986 there was a grand celebration of his eightieth birthday, attended by many friends and colleagues from all over the world, which also involved the endowment of an annual Prelog Medal and lecture. (The first lecturer was the distinguished U.S. stereochemist Kurt Mislow.)

Prelog was a cultured individual with broad interests in music, art, and literature, but he rarely bared his innermost thoughts and feelings. Thus it is particularly significant that, on the occasion of the birthday celebration, an earlier response of Prelog’s to a letter concerning religion emerged: “Dear …, Nobel prize winners are not more competent about God, religion, or life after death than other people but some of them, like myself, are agnostics. They just don't know and therefore they are tolerant to religious people, atheists, and others. What they dislike are militant zealots of any kind” (Arigoni, Dunits, and Eschenmoser, p. 459).

In 1996 Croatica Chemica Acta published a Festschrift in honor of Prelog’s ninetieth birthday with several articles reminiscing about his work in Prague, Zagreb, and his early days in Zürich. Prelog was generally in good health, though late in life afflicted with pernicious anemia kept under control with vitamin B-12. He was an ardent skier well into his sixties. He died at the age of ninety-one after a short illness. Many extensive obituaries and memoirs by colleagues, friends and historians (1998–2000) were published all over the world.

BIBLIOGRAPHY

WORKS BY PRELOG

“Chirality in Chemistry.” Science 193 (1976): 17–24. Nobel lecture. Also available fromhttp://nobelprize.org/nobel_prizes/chemistry/laureates/1975/.

“Why Natural Products?” Croatica Chemica Acta 58 (1985): 349–351. Concerning the continuing value of investigating natural products.

“Fons et Origo.” In Euchem Conference on Stereochemistry Bürgenstock, Switzerland, 1965–1989, edited by Monica and Rolf Scheffold. Aarau, Switzerland: Sauerländer, 1989. Concerning the Bürgenstock Conference.

My 132 Semesters of Chemistry Studies. Translated from the German by Otto Theodor Benfey and David Ginsburg. Washington, DC: American Chemical Society, 1991. A 120-page scientific autobiography with 114+ references, covering most of the work described above. The author is indebted to Prelog’s book for much of the information contained in this article.

“My ‘Nomenclature Years.’” In Organic Chemistry: Its Language and Its State of the Art, edited by M. Volkan Kisakürek. Weinheim, Germany: VCH, 1993.

OTHER SOURCES

Arigoni, Duilio; Jack D. Dunitz; and Albert Eschenmoser. “Vladimir Prelog.” Biographical Memoirs of Fellows of the Royal Society 46 (2000): 443–464.

“In Memoriam Vlado Prelog.” Chimia 53 (1999): 123–162. Includes a tribute by Albert Eschenmoser, a transcript of a 1988 German TV interview, and a complete list of Prelog’s 423 references.

“Inauguration der Prelog Vorlesung” [Inauguration of the Prelog Lectureship]. Chimia 40 (1986): 389–393.

Jones, J. Bryan, and John F. Beck. “Asymmetric Syntheses and Resolutions Using Enzymes.” In Applications of Biochemical Systems in Organic Chemistry. Part I, edited by J. Bryan Jones, Charles J. Sih, and David Perlman. New York: Wiley, 1976. See pp. 287–355 for the work of Prelog and collaborators.

Kauffman, George B. “In Memoriam Vladimir Prelog (1906–1998): Some Personal Reminiscences.” The Chemical Educator3, no. 2 (1998): 9 pp.

Kaufman, Teodoro S., and Edmundo A. Rúveda. “The Quest for Quinine: Those Who Won the Battles and Those Who Won the War.” Angewandte Chemie International Edition 44 (2005): 854–885.

Mislow, Kurt. “Vladimir Prelog.” Proceedings of the American Philosophical Society 144 (2000): 106–111.

Seeman, Jeffrey I. “The Woodward-Doering/Rabe-Kindler Total Synthesis of Quinine: Setting the Record Straight.” Angewandte Chemie International Edition 46 (2007): 1378–1413.

“Surprise Festschrift in Honor of Professor Vladimir Prelog.” Croatica Chemica Acta 69, no. 2 (1996): 379–739.

Woodward, Robert B. “Strychnine.” Journal of the American Chemical Society 69 (1944): 2250.

———, and William E. Doering. “The Total Synthesis of Quinine.” Journal of the American Chemical Society 66 (1944): 849; 67 (1945): 860–874.

Ernest L. Eliel