HISTORY 142 CHIMIA 2006, 60, No. 3

Chimia 60 (2006) 142–148 © Schweizerische Chemische Gesellschaft ISSN 0009–4293

Recollecting the Institute of Organic Chemistry, ETH Zürich, 1972–1990

Claude E. Wintner*

Jakob Schreiber In Memoriam

Abstract: The author recalls several visits to the Institute of Organic Chemistry, ETH Zürich. The faculty and staff of the Institute are remembered. Some circumstances surrounding the history of the publication of the total synthesis of vitamin B12 are mentioned.

Keywords: Institute of Organic Chemistry, ETH Zürich · Vitamin B12, total synthesis, publication

I believe I first became aware of the Ins- went on to the pioneering efforts toward Pennsylvania, which would be my home titute of Organic Chemistry (Laboratorium vitamin B12. Without being unduly humble base for the next 30 years, I finally was able für Organische Chemie) of the ETH Zürich about the accomplishments of American to arrange a sabbatical year with Eschenmo- only in 1959, when I was a first-year gradu- chemistry, I nevertheless can say with truth ser at the ETH. Two further sabbaticals, in ate student in the Department of Chemist- that in general the Swiss chemists of that 1976–1977 and 1989–1990, followed; and ry at Harvard University. I was working time possessed a technical mastery (from it is of these stays in Zürich that I now remi- in the research group of the man who was the Praktikum, or related academic structu- nisce. I believe that in 1972 in some sense almost universally considered the foremost res, quite apart from more experience) that I just may have caught the Institute and the organic chemist of that time, Professor Ro- we Americans indubitably lacked, and in city – indeed, the entire country – engaged bert Burns Woodward. At the postdoctoral this respect nearly all of them helped me at in a way of life in some respects largely un- level the Harvard department in general, one time or another. altered since sometime prior to the World and Woodward’s group in particular, were Early in my time at Harvard, then, I heard Wars; and so I will endeavor to sketch this very international in character. The Wood- of Albert Eschenmoser, the young chemist period in time just before dramatic shifts, ward Group had a large Swiss contingent, at the ETH who had just bested our revered already then clearly in the offing, would many of whose doctorates were from the boss in a friendly race to the finish line of lead to major transformations. ETH, and these coworkers were prominent the total synthesis of the complex alkaloid Change seems to move from West to among those who had spearheaded the total colchicine. Clearly, this was someone to East. In America so much begins in Cali- synthesis of chlorophyll (completed around be reckoned with! Not long thereafter I at- fornia, and moves eastward (if initially the time I joined the group) and who then tended Eschenmoser’s series of lectures at frequently jumping over the great midsec- MIT, on colchicine and related topics, and tion of the country). In the same way, much from then on the idea formed in my mind change – and, sadly, the bad with the good that I must sometime study and work at the – has come from America to Europe, if with ETH, quite generally acknowledged at that the delay of a decade or two. Switzerland time to stand with Harvard at the pinnacle in 1972 still retained many of its old ways, of the discipline of organic chemistry – and not least because it had not suffered physi- most particularly with the man who in the cal damage during the wars. Thus, Zürich field of natural products synthesis already as I and my family experienced it when we was Woodward’s greatest rival and who arrived in 1972 still was in many respects soon was to join with him in a collabora- – and even architecturally – a European city tion of equals to complete the total syn- of the early part of the century, and it was of thesis of vitamin B12, upon which both al- special significance to me that from it I was ready had embarked separately. This dream able to make a palpable extrapolation to the gained further definition when I interacted lives of my parents, who had grown up in with Vladimir Prelog, the Chairman of the prewar Leipzig and Budapest before com- Institute, while he held a six-week visit- ing to America in 1930. I think the same *Correspondence: Prof. Dr. C.E. Wintner ing lectureship at Yale University, where I was true of academic life as I experienced Department of Chemistry was a faculty member from 1963 through it at the ETH of that time. In the course of Haverford College Haverford, PA 19041 USA 1968. In 1972–1973, after I had moved to the year 1972–1973 I came to realize, in [email protected] the professorship at Haverford College, in ways I could not have before, how I was an HISTORY 143 CHIMIA 2006, 60, No. 3

American, and how American I was. At the same time I came to a better sense of how European in my perspective I also was, as a result of my background, and these Europe- an views became reinforced. In 1976–1977, at the time of our second stay in Zürich, the city – and also its academic life – already had begun to change profoundly. By 1989– 1990, my final year of residence in the city, an entire set of alterations had become ir- reversible. No value judgment is intended – only again the sense that I am chronicling a largely bygone era. At that time the entire ETH was located primarily in the Universitätsstrasse quarter (Photos 1 and 2). From the very first I was welcomed generously, above all by Albert Photo 1. Entrance to the ‘Altbau’ of the Chemistry Department Eschenmoser and Vladimir Prelog, but as well by a host of others. In 1972 the new chemistry tower at Universitätsstrasse 16 was just in the midst of construction, so dergraduate and graduate training at the that the teaching laboratories of the Insti- ETH. His brilliance was soon recognized, tute for Organic Chemistry, and in addition and his uncovering of the relationships that a few of its research laboratories, still were ultimately would blossom into the biogene- housed in the historic old, original building, tic isoprene rule, building upon Ruzicka’s the ‘Altbau’, shared with the inorganic and great work in this area, but reaching well physical institutes. However, most of the re- beyond it, had brought him to the attention search activity in organic took place in the of the chemical world early in his career. ‘Neubau’, the post-World War II structure Given the benefit of hindsight I now real- at Universitätsstrasse 8 built especially for ize that, just at the time of my arrival in the organic chemists under the leadership Zürich, Eschenmoser faced an interesting of the great Leopold Ruzicka (Ruzicka still and critical juncture in his career. The im- came to the labs to visit off and on in 1972, mense collaborative effort of the total syn- although by then he no longer was very ac- thesis of vitamin B12 had been completed in tive; I only met him briefly on a couple of February of 1972, and while there remained occasions). I was assigned one of the six some important matters to be worked out, desks in a long, rather narrow room near it seemed evident that Eschenmoser was at the old library in the Altbau. Three desks the same time searching for a new domain were held by ETH-Privatdozenten, and of research. It now is clear that I was pres- three by visitors. By some standards this ent at a pivotal moment: the end of Eschen- arrangement might have been considered moser’s efforts in the area of high-profile lacking in privacy, but in fact it provided organic natural products synthesis and the for an extremely stimulating atmosphere. beginning of his exploration of the self-as- We all respected long periods of relative sembly of the molecules of life, the project quiet (and, as I remember, there was only a that has occupied him ever since. One could single telephone, which we were careful to Photo 2. Chemistry Buildings on Universitäts- say that, having in the 1950’s considered strasse use only for quick incoming messages). At the question: How are the molecules of Na- the same time, scientific interactions were ture (at least, the isoprenoids) assembled? natural. Hans-Beat Bürgi occupied the ad- real productivity, than I believe is appreci- – and then digressed a while to answer the joining desk, and as the year progressed I ated, or at least properly acted upon, in the question: Am I able to assemble Nature’s witnessed at first hand the development of design of modern laboratories. During my molecules? (Yes!) – he advanced to ques- the ideas now summed up in the concept second visit, just four years later, the splen- tions that are considerably more profound: of the Bürgi-Dunitz trajectory for nucleo- did new tower was complete. Each member How did the molecules of Nature become philic chemical reactions at a carbonyl of the Institute had his own floor. I had my assembled in the first place? Why those par- function. own private office. I do not wish to imply ticular molecules? However, to emphasize As a result of crowding, all the groups that this second visit was not a success in all the point once again, little of this was appar- of the Institute worked on top of one an- respects, intellectually and otherwise – for, ent to me in 1972; I simply was visiting in other, so to speak, the consequence being as will be seen below, quite the contrary the research group of one of the few organic an environment with a great deal of intel- certainly was true – but it was undeniable chemists in the world – indeed, perhaps the lectual cross fertilization. In addition, just that the frequency of random interactions only one at that moment – who stood on an above our office, on the top floor of the Alt- had been curtailed, and that I had to resort equal footing with Woodward. bau, was the ‘Chemie Bar’, the Institute’s much more to meeting with people by ap- Certainly Eschenmoser led his labora- cafeteria, where throughout the workday pointment than had been true earlier. tory, but at the same time there were two one found lively chemical conversations, Albert Eschenmoser is an extraordinary lieutenants who, in fact, oversaw essen- accompanied by coffee and food. Architec- man. The son of a butcher, he grew up in tially every practical aspect of its experi- ture has much more influence on the easy Canton Uri and attended Oberrealschule mental operation: Jakob Schreiber (Photo movement of scientific ideas, and hence on in St. Gallen before receiving both his un- 3) and Dorothee Felix. Neither one spent HISTORY 144 CHIMIA 2006, 60, No. 3 more time on theory than necessary; on the bility infuriated him to the core of his thrifty other hand, if I think of the most accom- Swiss spirit). By that time a heart problem, plished all-around experimentalists I have which he treated only with nitroglycerine, met in my life as a chemist, these two stand had advanced; he suffered chest pain when alone for me at the top (and, indeed, they walking up even a modest incline. Not long trained a number of the other gifted experi- thereafter Schaggi Schreiber died of a mas- mentalists I have known). As a young man sive heart attack, fittingly as he was sawing Jakob (Schaggi) Schreiber had trained as a down trees near the Waldhüsli in Dietikon. forester, coming relatively late in his life In all he was a prodigious personality. to the ETH, as a result of the good offices Although she, too, is as Swiss as Swiss of a man in his village who recognized his can be, and also an early Eschenmoser doc- scientific abilities. It needs to be empha- toral student who spent her entire career with sized that under the relatively restrictive the group, in some respects one would be mores of the Swiss society of that time, hard pressed to invent a more polar opposite both academically and socially, this was to Schreiber than Dorothee Felix (Photo 5). quite an unusual circumstance. Although Above all she was a technically proficient Schreiber was more or less Eschenmoser’s and scientifically confident woman in a na- age – in fact, somewhat older – he had been tion which in 1972 barely had come around Eschenmoser’s first doctoral student. When to granting women the right to vote in its the two were together, one always sensed elections – and even then still not in some Photo 3. Jakob Schreiber Photo: P. Häfliger the exceptional bond that existed between cantonal ones – a society where it was taken them; while I have no real evidence, I sus- for granted that the fundamental concerns pect that each had a special empathy for the in this status he shared a stake in a ‘Wald- of women were limited to the holy triad other as one who had risen from relatively hüsli’ where Eschenmoser group festivities of Kinder, Kirche, Küche (a conception in humble roots in an era when it still was true could be held. Especially for this purpose which Schreiber believed fervently). Where that so many in academic life, and perhaps he had constructed from heavy gauge stain- Schreiber grew up in the countryside, her especially in European academia, came less steel a one-of-a-kind grill in the shape background is Stadt Zürich, through and from the more comfortable upper middle of a porphyrin ring, and this was brought through – careful, prosperous, frugal. Once, classes, if not the upper class. Schreiber out with ceremony at all group occasions. during the summer of 1991, I spent a few stayed on, devoting his entire career to the Moving well ahead in time, for his 70th weeks as a guest in her lovely home while Eschenmoser lab. I think it is fair to say that birthday I had obtained an authentic GM Eschenmoser and I were finishing some otherwise he might have had a successful, poster of the vintage Corvette sports car writing. In all ways she was a most gener- but nevertheless relatively prosaic, career he had driven during a research stay in the ous hostess, but nevertheless I insisted on in the Swiss chemical industry. As it was, States, at NIH. Not to be outdone, he made doing my share. We cooked breakfast and with his extraordinary practical intuition for me in return the splendid, also one-of-a- dinner together, and I did my share of the and manual dexterity, he made possible kind , corrin grill (Photo 4) – as opposed to shopping. Noting a lack of salad oil in the for Eschenmoser and for countless gradu- porphyrin, a difference, of course, of just a house, I brought home from Migros some ate students and postdoctoral fellows what single carbon atom – which my family uses ordinary olive oil. Dorothee’s comment: otherwise might have been technically un- on festive picnics at our summer cottage in “So ein edles Öl ist fast nie in diesem Haus attainable (it should not be forgotten that it New Hampshire. During my last visit to the gewesen!” was Schreiber’s hands which had enabled ETH, in 1989–1990, I visited the home in Felix was, for all efforts employing the the younger group at the ETH to best Wood- Alvaneu, in the Albulatal, which Schreiber technique of gas chromatography in the ward and his collaborators in the colchicine had built for his family almost entirely with group, what Schreiber was for high-pres- race.) Schreiber was the first to transform his own hands, and mostly from brand-new sure liquid chromatography: the source of high-pressure liquid chromatography from material discarded at construction sites – a authoritative information and experience a relatively obscure analytical method to a fact that gave him enormous satisfaction that could, and often did, spell the differ- working technique usable for synthesis, just (although the phenomenon of its very possi- ence between success and failure. Despite in time to overcome problems of separation that promised to present insurmountable practical obstacles on the path toward vi- tamin B12. The credit for pioneering in this area (as opposed to developing a commer- cial instrument) that the Waters Corporation received at the time was misplaced. A big, gruff man, of enormous physi- cal strength, Schreiber was a person of deep integrity and unfailing generosity, totally devoted to the greater cause of the group and, beyond that, to the entire chemical en- terprise at the ETH – for example, he made major contributions toward the design of space in the new chemistry tower at Uni- versitätsstrasse 16. In addition to being a Forstmeister, he served as Jägermeister (responsible for, among other matters, the census of deer and the culling of the herd) Photo 4. Albert Eschenmoser, the author, and Jakob Schreiber, with the in his town of Dietikon, outside Zürich, and corrin grill made by Schreiber for the author HISTORY 145 CHIMIA 2006, 60, No. 3

Photo 6. Engelbert Zass and Hermine (Gächter) Zass

Photo 5. Dorothee Felix all their differences in background and temperament, the two were extremely close friends, above all united by their loyalty, al- truism, and devotion to the group. Unques- tionably, they ran the lab as a duo. Every af- ternoon, promptly at four, Dorothee would make tea for herself, Schaggi, her appren- tice students, ‘der Chef’ (Eschenmoser), and any visitors, such as myself. Cookies were Photo 7. Duilio Arigoni and Vladimir Prelog served, and the discussion, though often of group matters, might cover almost any owed the extraordinarily attractive apart- by all the honors he received in his lifetime. topic, especially the Swiss political scene. ment we lived in on Clausiusstrasse during I immediately renewed my acquaintance Dorothee also maintained plants and flow- our second stay. She also found for me the with him, and with Dunitz, whom I likewise ers throughout the entire laboratory. Once, similarly excellent flat on Hochstrasse in had met at Yale when he lectured there for a when I took over the watering duties for her 1989–1990. As with Felix and Schreiber, few weeks (Yale had tried, unsuccessfully, for a few weeks in her absence, I found out over the years Hermie and Engelbert Zass to hire Dunitz at that time). I also quickly just how many there were! Always an active became our close friends. came to know Arigoni, whom until then I member of the Swiss Alpine Club, she still Other than Eschenmoser, the three mem- had not met. His quickness and incisiveness continues to hike and ski avidly. bers of the Institute with whom I interacted of mind (in five languages) were breathtak- A third pillar of stability in the group extensively were Vladimir Prelog, Jack Du- ing. was Fräulein Hermine Gächter, soon to nitz, and Duilio Arigoni (Photos 7 and 8). Let me now attempt to give a sketch of become Frau Zass (Engelbert Zass was an It was still three years before Prelog would Eschenmoser Ph. D. who has stayed on at be awarded the Nobel Prize. When he had the ETH, in the broad area of informatics) taken over the chairmanship of the Institute (Photo 6). Hermie Zass has handled essen- at Ruzicka’s retirement, Prelog had initi- tially every aspect of Eschenmoser’s corre- ated the process of ‘Americanizing’ what spondence, publication, and administrative had been until then a traditional Germanic life for more than thirty years. Her skills (in structure with a single all-powerful Head; three languages and a dialect), efficiency, by the time I arrived, the Institute consisted and diplomacy were, and are, simply as- of eight Full Professors having equal sta- tounding. A complex manuscript that by any tus (D. Arigoni, J. Dunitz, A. Eschenmoser, normal standard might have taken a person E. Hardegger, O. Jeger, J. Oth, V. Prelog, a week to type would be completed in an W. Simon). Also on the American model, afternoon. Errors? For all practical purpos- the position of Chairman rotated, although es, there never were any; they simply are Prelog unquestionably still was seen as the not permissible in her world view! Beyond wise leader and father figure of the entire this, she attended to myriad administrative Institute, with Ruzicka being, so to speak, matters for us all in the group, always seem- the grandfather. It is hard for me to recall a ing as if she had nothing else to do. It was warmer, more generous person than Prelog, to her effective searching that our family who remained personally entirely unspoiled Photo 8. Jack Dunitz HISTORY 146 CHIMIA 2006, 60, No. 3 the rhythm of a typical day for me at the constructing a lecture, and never again in course, German, and all lectures were deliv- ETH. I tended to get up very early, well be- my career would I lecture toward specific ered in this language, despite the fact that it fore dawn, and take some exercise on the short-term hour examination material. was, in fact, the true mother tongue only of track at a school near Hotzestrasse, where Prelog soon began a tradition of treat- native Germans and Austrians. Some group we lived. I then helped my wife get our ing me to Kaffee und Kuchen nearly every seminars were conducted in English, both sons up, and we all would have breakfast day at the Chemie Bar. Here I must digress because there often were many American together. Often I used the tram to get to the for a moment regarding some Swiss cus- and British (and some Asian) postdoctoral ETH. Because we lived at Schaffhauser- toms that regulated the structure of the day. fellows and perhaps even more because the platz, where several branches of the Zürich Most people ate an early breakfast (Früh- faculty recognized the value for their stu- transportation system come together, there stück) and were at work betimes – as early dents to be able to communicate fluently in were many options, each providing for me a as seven o’clock, certainly by eight. Then, scientific English. Prelog’s native language projected (and nearly always real!) elapsed quite universally, sometime between nine was Croatian, although his German was es- time of service of about twenty minutes. and ten, everyone had a snack time – Znüni sentially perfect. His English was fluent as I could take the 14 or the 11 to Central, (zum neun). Children went off to Kinder- well, if riddled with small errors, compa- connecting with the 6 or 10 to ETH. Alter- garten each day with a special Znünitäschli; rable with mine in German. Nevertheless, natively, I could hop on the 7 or the 15 to I still have my younger son’s from 1976. in this circumstance it was natural for us Haldenegg (one stop above Central), again For adults the standard Znüni was a cup to speak English together. Dunitz too spoke connecting with the 6 or 10. Finally, there of coffee and a sweet roll or some yogurt. excellent German, and he delivered fluent was the possibility of the 33 trackless trol- Mittagessen, on the other hand, was a meal lectures in that language. However, since ley bus from Schaffhauserplatz to Seilbahn- in flux. Traditionally this had been the big he was a Scot, the language spoken around Rigiblick, followed by the 9 or the 10 (but meal of the day. People went home, from him more often than not also was English, now in the other direction) to ETH. In 1972 work and from school, to eat, to have time and obviously the two of us spoke English the charge was just 70 Rappen (Centimes), with family, and to rest. The entire process with each other. so less than twenty cents at the rate I had might take two hours. However, this cus- More interesting were the circum- changed my money on arrival, and about tom clearly was at odds with the pace of stances arising from the very real conflict thirty after the dollar’s fall (to which I shall ‘modern life’, and by 1972 many people among Swiss Germans about what their na- return). However, just as often I walked. took their midday meal at their place of tive language really is, and I shall return to The elapsed time was more like half an work (although children still came home this subject in somewhat more detail when hour, but I found great pleasure in observ- from school). At four one broke again, for I relate our children’s experience. Schrei- ing the Zürich scene as I went along. Zvieri (zum vier). Again, coffee, but now ber, Felix, and Eschenmoser invariably At the Institute Schreiber had assigned generally with something really sweet, for spoke with each other in dialect; for them me some lab space in the Neubau, near example, a nice piece of Torte or Kuchen. to speak High German among themselves his own, and I began a few experiments Work then continued until six or even sev- was unnatural. However, when an English- on work that continued from Haverford. en. Abendessen at home traditionally was speaking guest was present, the dialect gen- However, my heart was not really in this, quite a light meal. In sum, the traditional erally could not be an appropriate medium and so I soon gave up the experimental work day might cover twelve hours, of of communication, and instead the con- work entirely, realizing how much more I which close to four were engaged in meal versation at the entire table almost invari- could profit instead from the lectures, both breaks. One cannot help but find this a civi- ably would switch to English, not German, graduate and undergraduate, as well as the lized schedule; nor, on the other hand, were even if (which was certainly by no means group seminars, regularly given by my ex- the Swiss ever known for not getting work the rule!) the English-speaker could under- traordinary new colleagues, while concom- done! Prelog gladly would have taken me stand and speak German. I was able, after a itantly committing myself to extensively along to both Znüni and Zvieri, but because while, to follow the dialect reasonably well, reading the literature in association with I often had tea with Felix and Schreiber in if never perfectly, but to actually speak it these offerings. I gained a new perspective the afternoon, Znüni (for Prelog, custom- properly out of the depths of the throat was on undergraduate teaching, for the lectures, arily, at ten) was more usual for us. I was quite beyond my reach (in fact, somewhat on the European model, were designed to particularly fond of a chocolate-covered ha- the same circumstance regarding the dialect provide students with a comprehensive zelnut ‘Hörnli’, generally with a cup of tea. held for Prelog, Dunitz, and even also for knowledge, to enable them to pass disci- Sometimes others would join us, especially Arigoni, though he was Swiss, from Ticino, plinary examinations after two and four Arigoni. As I already have indicated, Prelog and fluent also, as I already have indicated, years rather than individual one-hour and always insisted on paying, no matter how in German, French, English, and Spanish, final examinations on a per-course basis, many people were in the party (“Ich bin as well as his native Italian; in general, only as in the American system. I do not wish to ein reicher Mann!”). Indeed, since he was a the German-Swiss can handle their own di- overstate the differences, for the students member of Ciba’s board of directors – and alect effortlessly). Appreciating, however, still, indisputably, were compiling facts, if also even possessed a kilo of pure gold in how much this particular American wished for a distant and potentially overwhelming prize medals – no one ever worried about to immerse himself in another culture, my examination. Nevertheless, on the whole his financial stability as a result of these Swiss friends generally did me the enor- attendance was excellent, and there was a outflows. Prelog always went home for his mous honor of communicating with me in refreshingly open and inquiring attitude, in Mittagessen. Mine at the Chemie Bar fre- German, mostly (except, sometimes, for contrast to the reflexive and so frequently quently was with Eschenmoser, Dunitz, Fe- Dorothee Felix) suffering in silence my intellectually defeating intensity which lix, and Schreiber, and generally focused on grammatically incorrect, if reasonably flu- regularly builds up in an American college chemical topics; Dunitz and Eschenmoser ent, renderings. Perhaps the saving grace for classroom with each successive assignment shared research ideas constantly. me in Switzerland has been that the Swiss and hour-examination within a relatively In this context I should mention the lan- do not worry too much about perfect Ger- narrow time frame, culminating in a final guage spoken, for this depended on the com- man grammar. Indeed, in the dialect, many examination centered on a single course, pany and the situation, and might be dialect, of the inflections are hidden. In any event, which then is ‘done’. From my own point German (that is, Hochdeutsch), or English. my efforts to join the community in this lin- of view I took home a new philosophy of The official language of the Institute was, of guistic sense, even if imperfectly, differen- HISTORY 147 CHIMIA 2006, 60, No. 3 tiated me from most – sadly, indeed, nearly (to an American) to run largely on a cash Americans reasonably could, without being all – other Americans. Both at the ETH and basis. For example, I was astounded to dis- expatriates, to becoming a Swiss family, not in the larger society, and certainly not least cover that the graduate student teaching as- least because of our ETH friends, as I now because of my wife’s essentially flawless sistants at the ETH were paid in cash. On shall relate. Our older son was assigned to German (the result of her previous graduate pay day the departmental secretary would the Schulhaus Huttenstrasse, an excellent study in German literature), we were wel- go to the bank and withdraw literally tens school located just up Universitätsstrasse comed as Americans with a distinctly Eu- of thousands of francs, which she then dis- from my office, and to his age group, which ropean outlook, ultimately allowing us to tributed to the students in envelopes. Few in Zürich was the first grade, Erste Klasse. develop a very special set of relationships people had a checking account, and they This had commenced already the previous that have been close and lasting. walked about with what seemed to me to be April, as still was the Zürich custom at that As a seasoned veteran of the wars of stu- enormous sums – several thousand francs time. It is in Erste Klasse that, immersed dent unrest in the United States, it was inter- – in their pockets, a habit that we would as into a cold bath, the children begin their esting for me to observe the initial stages of see change within a period of just a few study of High German, which is to them, to similar troubles, which in 1972 only were years. Even I came to think nothing of car- a far greater degree than might be realized, beginning to loom within the Swiss bastion. rying four or five hundred francs, whereas a completely foreign language. I found (and I tried to lend some warning and useful ad- in America I never would have considered so did my wife, even with her grammati- vice, but perhaps quite understandably – for having more than thirty or forty dollars in cally perfect German, and also my mother, Switzerland had, after all, fended off in- my billfold. Of course, to place a value on native German speaker that she was) that volvement in two World Wars! – my Swiss 500 francs in the Swiss society compared young children in Zürich often could not colleagues could not yet really comprehend with 125 dollars in America at that time, was understand a word I said, this being due the phenomenon of students confronting not easy, just as today the equivalent exer- not so much to my accent as to the fact that their teachers, seeing this as an American cise is not, for this varied considerably with the spoken words of Hochdeutsch and of aberration, transplantable perhaps to Ger- the goods and services involved. Clothes Züridütsch simply do not sound at all the many and France, but not to Switzerland. and meat, for example, seemed extremely same, not to speak of their varying gram- On the whole, they were of the opinion that, expensive; rent, despite Swiss complaints, matical and syntactical constructions. Thus, “It can’t happen here”. They were wrong, less so – ours was 600 francs; transportation our son was learning German as a foreign and unfortunately they were fated to experi- and milk products, subsidized by the state, language, but so were all the others in his ence over the next few years, if rather less were a bargain. class, and in this sense it was essentially violently than their colleagues in Germany, Little did I know when I made my un- no harder for him, especially as after the just how incorrect their assumption would avoidably large transaction – which had summer break the dialect quite specifically prove to be. seemed to me somewhat risky and irrevers- no longer was used in the classroom by the Throughout the year I helped both ible at the moment – how serendipitously teacher, except under urgent circumstances, Eschenmoser and Prelog with various proj- favorable my financial arrangements soon for which, in his case, she was able to speak ects, on the surface mostly with matters hav- were to prove. By bringing in our money all English to him when absolutely necessary. ing to do with the proper English rendering at once and changing it at the beginning, I However, this was only half the story, of their Germanically inflected texts, but had, effectively, turned us into a Swiss fam- for the moment the children went out to the in the process I was able to become much ily for the year. When, later that fall, the school yard, dialect was the only language closer to them and to the work taking place first great ‘oil shock’ hit the world financial spoken. After some days it came out hesi- in their groups. Indeed, my perspectives in markets as a result of the pull-back in pro- tantly from our son that he was being en- organic chemistry as a whole were very sig- duction by the Organization of Petroleum- tirely left out of all the games, and that he nificantly broadened by these interactions. Exporting Countries, the exchange rate of found himself unable to break in. Asking Quite randomly, off and on Eschenmoser the dollar vs. the Swiss franc fell within a their advice, I outlined this situation to Ja- generously would add a thousand francs to period of just a few days from four-to-one kob Schreiber and Dorothee Felix at lunch in our budget – presumably when there was to not much above two-to-one, finally set- the Chemie Bar. First, after some extended some grant money left over, although I don’t tling at about 2.3. Suddenly it took 225 dol- debate, as I remember, they agreed upon the believe I ever asked him about the source. lars, not 125, to buy the same 500 francs! best formalism for the circumstance. Then, This never was in response to any request Essentially overnight, all my American col- with considerably more effort, they taught from me, for it certainly had not been part of leagues at the ETH who were on a regular me to say, so that I could transmit the ques- our agreement, nor did I actually need this monthly dollar stipend from the States had tion to our son: “Hchan-i-au-miitmache?” money, but in fact it allowed the Wintners only half the buying power they had had the That is, in High German: “Kann ich auch a few extra little extravagances in our new day before, and indeed many felt forced to mitmachen?” – “Can I join in?” (This is all Swiss life. All in all, we felt as though we return home within a month or two. How- run together, starting with the “Hchan” far, were very wealthy, in that we were able ever, for us, living frugally on a Swiss franc far back in the throat, the first “i” short, the to do essentially everything we wanted to budget in a Swiss franc society, and with no double-“i” more, though not exactly, like an do. In this respect, however, I might add an new dollar income, there was essentially no English long “e”; and, indeed, the written extra note, for 1972–1973 was no ordinary effect, except the psychological one of real- similarities between the renderings I have year in the currency markets. I had arrived izing that a cup of coffee now cost a dollar attempted actually are greater than are the with a bank draft for $9,000, which was all and a half – and we quickly learned not to oral). I went home and practiced this with we had to carry us through the nine months think this way! Indeed, this set of circum- our son. Our landlady then coached him of our intended sojourn. Sometime in Oc- stances actually was just another aspect of further in pronunciation. This was all that tober this was converted by the Bankverein the year that made us more ‘Swiss’ than I was needed; it worked like a charm upon in one lump sum into somewhat more than ever had imagined would be the case. its very first use, and from then on our son 35,000 Swiss francs – so, at an exchange We returned to Zürich in 1976–1977 made friends. rate of almost four-to-one. This, then, was with the help of an American-Swiss Foun- My activities at the ETH during this our hoard for the year, to be budgeted at dation grant which I was able to obtain with year were extremely rewarding. With Pre- 4,000 francs per month. Eschenmoser’s support, and it was during log I began the work that was to lead a few At that time the entire society appeared this year that we came perhaps as close as years later to my little paper on two-dimen- HISTORY 148 CHIMIA 2006, 60, No. 3 sional chirality (J. Chem. Educ. 1983, 60, cal A-D coupling approach conceived and 587. Our interaction renewed my desire to 550). Of greater significance, Eschenmoser executed solely at the ETH; in this sense it work with him once again at the ETH. By and I wrote the paper for Science that, to could, and did, stand alone. Furthermore, 1989 I was feeling somewhat worn down this day, remains the sole ‘scholarly’ ac- material gained by means of this route actu- by a relatively heavy administrative and count by Eschenmoser in English of the ally had been used to first complete the final teaching load at Haverford, and so when great ‘ETH route’ to the pinnacle of the steps. However, this ‘ETH route’ had re- Eschenmoser invited me to return to Zürich total synthesis of vitamin B12. Although it ceived considerably less publicity, although in 1989–1990, I jumped at the opportunity. is clear that for the most part my contribu- Eschenmoser had summarized his group’s I worked with him on his HOMO-DNA tions had to be limited to the structural and achievement in an article in Naturwissen- project, as well as on an appreciation of linguistic spheres, as opposed to the scien- schaften 1974, 61, 513, also essentially the Woodward’s chlorophyll synthesis and the tific, I actually am very proud to have been transcript of a lecture he had delivered in Woodward A-D ring strategy for the vita- a participant in the writing of this article Zürich to the Zürcher Naturforschende Ge- min B12 synthesis, initially conceived as a (Science 1977, 196 (No. 4297), 1410), for I sellschaft. contribution toward a planned obituary for think it probably would not have appeared While Eschenmoser naturally had hesi- Woodward. The obituary ultimately took at all – that is, in English and in Science tated to move forward further under these another form, and we did not publish this – had I not been on the scene in 1976–1977. circumstances, I strongly encouraged him work, although, when I returned to Haver- Nevertheless, it never has been lost on me in his own vision that he might at least write ford, I incorporated the perspectives given that Eschenmoser’s coworkers in the B12 an overview for Science, an expansion of me by this study of the chlorophyll synthe- effort may have wondered how my name the Naturwissenschaften article, and espe- sis into a new course offering. came to appear with his on this article, for cially in his idea to include additionally Taking my midday meals with my clearly I had made no experimental or theo- what had not appeared in explicit form in friends at the ETH – Dorothee Felix and retical contribution to the work. Briefly, the Naturwissenschaften: a full formulaic re- Jakob Schreiber, Hermie and Engelbert circumstances were as follows. action scheme for the ‘ETH route’ with a Zass, Arigoni, Dunitz, Prelog, Eschen- By 1976 Eschenmoser found himself table of the experimental conditions for moser – and in the evenings dining with in a complex position. The total synthesis each individual reaction step as well as the students at the Mensa (my wife could of the vitamin had been a fully collabora- the reference to the ETH thesis where the not leave her teaching position in America tive effort, commanding the essentially un- corresponding detailed procedure could be that year), once again I came to feel almost divided efforts of both laboratories and a located. In sum, my role evolved to some Swiss, as I savored all the small delights of hundred chemists for well over a decade, extent from what had begun as that of sim- Zürich. Also, my German had become more and a collaborative report was warranted. ply a translator or editor to one where I was and more instinctive (even if grammatically However, four years already had passed what I might term – lacking a better word hardly less imperfect), and I actually began since the completion of the synthesis, and – a companion in the somewhat enlarged to dream in German. Finally, I might add Woodward, now sixty years old, still had enterprise of bringing out the Science paper. that this was an extraordinary period for not published a full theoretical and ex- In contrast to Eschenmoser, who doubtless Europe, not to say the entire world: on 9 perimental paper – as opposed to a com- was too close to the matter emotionally, it November 1989 I watched on television munication – on chlorophyll, at that point was my own opinion that Woodward could as jubilant crowds began to stream freely sixteen years in the past. Clearly adding to not, and would not, be offended if this ac- through the Berlin Wall at ‘Checkpoint the problem was the fact that throughout the tion were taken. I think my intuition in this Charlie’. period of the ongoing synthesis Woodward regard proved to be correct. I saw Wood- My years in Zürich broadened profound- had quite regularly communicated on its ward for the last time in June of 1979, when ly my intellectual perspective as a person, progress, by means of published lectures I stopped by his office one afternoon, just and certainly also as a chemist and teacher. (without experimental parts, of course), before flying out of Boston on a trip. He I suppose that as a chemist I remain above culminating in his IUPAC lecture in New was in an expansive mood, and we talked all the product of my study with Woodward Delhi (1972), where the successful conclu- for several hours. In the course of the con- and, as a teacher, of my apprenticeship in sion was announced. However, in the four versation he made clear to me several times teaching with William Doering when he intervening years even the appearance of a not only that he was not affronted, but – on was at Yale. But at the same time I cannot more formal, joint preliminary communi- the contrary – that he had been pleased, and acknowledge strongly enough the collegial cation with Eschenmoser, with at least the even relieved, that we had published the mentoring I received over a period of more customary skeletal experimental summary, Science article and thereby clearly delineat- than two decades from so many people at had been postponed. ed Eschenmoser’s great, and independent, the ETH, and above all from Albert Eschen- On the other hand, there was the further contribution. When I returned to Boston, on moser and Vladimir Prelog. complication that in the course of the un- July 10, I was handed Woodward’s obituary dertaking two routes in fact had been devel- in the Boston Globe from the day before. Received: December 15, 2005 oped. One was the fully joint effort, making I spent the academic year 1984–1985 on use of Woodward’s famous ‘Western’ (A- sabbatical leave at Harvard, where I taught D) half, and Eschenmoser’s ‘Eastern’ (B- the large undergraduate course in organic C) half, as well as the ETH coupling meth- chemistry, Chemistry 20, in the fall semes- odology (and, of course, the inestimable ter and was entirely free of teaching duties contribution of Schreiber’s HPLC), and it in the spring. As it happened, that fall I over- was this work that had been so highly pub- lapped for several months with Eschenmo- licized; indeed, by means of the aforemen- ser, who also was in residence at Harvard, tioned published lectures Woodward had holding the then-newly-created Woodward presented a fairly comprehensive outline of Visiting Professorship. Eschenmoser sug- this fully collaborative route to vitamin B12. gested I write an article for undergraduates The second route, while it too relied on the on bent bonds, a subject that had intrigued collaborative vision in its final steps, nev- him for some time, and the result was a pa- ertheless had at its heart the photochemi- per published in J. Chem. Educ. 1987, 64,