A AUTOBIOGRAPHY

Carl Djerassi Department of Chemistry Stanford University, California 94305

How does one write an autobiography - especially one dealing with scientific accomplishments - without appearing to blow one's own horn? I do not believe that this is possible. Of course, I could have refused the editor's invitation, but I am approaching an age when reflection and contemplationbecome a virtue rather than a luxury. Hence this will be the only caveat emptor of a story starting in the summer of 1942.

Because of an early skiing accident which eventually led to a knee I was ineligible for military service and had the luxury of a college education while most of my contemporaries ended up in the armed forces. I had graduated early from Kenyon College in not yet 19, and had started working as a junior chemist at CIBA Pharmaceutical Products, Inc. in New Jersey. As luck would have it, I worked for one year with Charles Huttrer, another Hitler refugee from Vienna, who though 20 or more years older than I, treated me like an equal. Together we discovered one of the first antihistamines - Pyribenzamine. The rapidity of the success and the fact that within a few years it became the drug of choice for hundreds of thousands, if not millions, of allergy sufferers spoiled me permanently. I became an inveterate optimist as far as scientific success is concerned.

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For financial reasons I had to work immediately after college graduation. Initially I intended to take graduate classes at night while working during the day. One semester of train commuting after work from New Jersey, to downtown New York City (in order to take classes at New York University and the Brooklyn Polytechnic Institute) convinced me that this was no way to get a graduate degree in a hurry. at the end of my first year at I decided to accept a WARF research fellowship at the University of Wisconsin for work towards a Ph.D. degree. The Swiss parent of CIBA was one of the original powerhouses in steroid chemistry and medicine, the work having been directed in Basel first by K. Miescher and later by A. Wettstein. Thus, even though my first year at CIBA was dedicated exclusively to antihistamines, I was exposed to through contacts with some of my laboratory colleagues. I also read the first edition of Fieser's "Chemistry of Natural Products Related to Phenanthrene." This highly readable book, more than any other got me permanently hooked on steroids.

In 1943, the University of Wisconsin Chemistry Department had two young assistant professors, A. L. Wilds and W. S. Johnson, who were about to undertake ambitious projects dealing with the total synthesis of steroids. At that time only one steroid hormone had been synthesized totally - equilenin - and Wilds was one of the members of the famous Bachmann, Cole and Wilds team which had completed that synthesis at the University of Michigan. I chose Wilds as my Ph.D. thesis advisor and announced rather brashly that I intended to get my Ph.D. degree in two .years. After all, the University of Wisconsin catalogue specifically stated that the minimum residency requirement for a Ph.D. degree was six semesters and by staying in school for both summers, I thought that I would satisfy the legal requirements. Professor Wilds, in his usual disarmingly mild manner, pointed out that in addition to the bureaucratic requirements and passing all of the preliminary examinations, I would also have to complete acceptable research for a Ph.D. thesis which could hardly be guaranteed in two years. I nearly did not make it - not because of my research, since I was both lucky and also had considerably more laboratory experience than the other graduate students as a consequence of my year at CIBA - but because I failed the inorganic "prelims." After studying inorganic chemistry very hard for the next semester, I passed the second time. My Ph.D. thesis project represented a compromise between Wilds's interests in total synthesis and my budding one (based on the Fieser book and CIBA lore) in steroid chemistry: the partial aromatization of androgenic steroids to the estrogens. In retrospect, this choice had an amazingly long-term chemical effect on me.

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Wilds's advice - study a model reaction for such partial aromatization- was first class. He suggested as the precedent the known acid-catalyzed conversion of the sesquiterpene santonin to desmotroposantonin and we applied it to a totally synthetic chrysene derivative (1).

I not only succeeded in synthesizing 1 and in proving the structure of the aromatization product 2 by total synthesis (1) of a chrysene derivative,but we also coined the generic term "dienone- phenol rearrangement" which became the title of my Ph.D. thesis and eventually became the accepted generic term in the chemical literature for this type of reaction.

The second model was the preparation (2) of steroidal 1,4-dien-3- -ones as a result of which I had to re-examine in detail Butenandt's originally published polybromination of 3-ketosteroids. Finally, I studied (3) the partial aromatization of 1-dehydrotestosterone to estradiol, although here we had been anticipated by Inhoffen's work in Germany (4). A thousand papers and forty years after my original four Ph.D. thesis publications (1, 2, 3, 5) in the J. Am. Chem. Soc. I still find myself publishing papers in the steroid field.

In the end I did manage to get my Ph.D. in two years, shortly before my 22nd birthday, and I returned to CIBA for another four years. While I resumed work on antihistamines and did other medicinal research, I was also able to continue my steroid interests on the side. For four years I worked first with one, and later with two women laboratory assistants - the last one (in 1949) a recent Mount Holyoke College graduate, Frances who eventually became Director of Laboratories at Columbia University.

I resumed work on steroid halogenation (6) and dehydrohalogenation (7) and started to publish on my own. I had planned to establish a reputation in chemistry in an industrial laboratory which would then permit me entry into academia at a more

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advanced level. This turned out to be naive because at that time moving from industry to academia was a one-way street going in the wrong direction although a few chemists (e.g., John Sheehan in going from Merck to MIT) showed that it was not impossible. At the ripe age of 25 I had had over four years of industrial experience and concluded that I was ready for an academic position. I had absolutely no luck although I did get an interview trip to lowa State College. I remember proposing seven or eight different research topics as evidence of my interest in various areas of organic chemistry but I was turned down almost brusquely. In retrospect, this was probably the best event that could have happened to me since indirectly this discouraging refusal led me much faster into a top academic position.

Several bench chemists from Schering and Hoffman-Laßoche established a private circle - we got together socially and also compared notes on how our respective chemical employers treated us. These were exciting days of steroid chemistry, especially since the anti-arthritic properties of cortisone had just been discovered and I was anxious to work on an improved synthesis of cortisone at CIBA. Unfortunately, or really fortunately, permission was not granted sinced most of that work was being conducted at CIBA in and when one of my Schering Martin Rubin, proposed me for a possible job at in City, I did not reject such a possibility completely out of hand - crazy as it sounded. Not only had I never heard of Syntex, I had never heard of anybody doing any chemical research in Mexico except for a few papers by Russell Marker. However, when I received an invitation to visit Syntex in with all expenses paid and no other advance commitment, I accepted. I had never been to Mexico and as a bonus decided to include a visit to in my tourist itinerary. Hungarian-born and Swiss-trained (ETH under the famous Leopold Ruzicka) George Rosenkranz, the Technical Director of Syntex, absolutely charmed me both personally and professionally. Furthermore, he made me an offer that was really tempting: work in Mexico City on a possible synthesis of cortisone from the steroidal sapogenin with half a dozen Mexican collaborators and in laboratories that were amazingly well equipped. They had a Beckman DU ultraviolet spectrophotometer (just a few years ago, the University of Wisconsin Chemistry Department bad none, and I had to run my own U.V. spectra on an instrument in the Chemical Engineering Department provided Professor Wilds accompanied me personally) and the first Perkin-Elmer single-beam IR instrument, which I learned to use in a crash course at Dobriner's laboratory at the Sloan-Kettering Institute in New York. CIBA had no infrared instrument at that time!

The two years spent at Syntex were among the most productive ones of my chemical career. During that time I was the author or co-author of some sixty papers on topics that were far from trivial. For instance, my early interest from Ph.D. thesis days on brominations and dehydrobrominations led to a new approach to A4-3-ketosteroids (8) - a key step in our eventual cortisone synthesis; we developed an excellent new way of synthesizing estrone and estradiol (9) as well as

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equilenin (10) from readily available androstanes; we published the first partial synthesis (11) cf cortisone from a plant sterol beating international competition "from Harvard"," Merck, , etc. While this partial synthesis of cortisone from diosgenin did not lead to an industrial process - the' Upjohn microbiological route was introduced shortly thereafter and became the method of choice - our second synthesis (12) of cortisone from hecogenin, a waste product from sisal, did become the basis of a cortisone synthesis which Glaxo (under license from Syntex) commercialized using East African sisal. To top it all, we completed all of the initial work on 19-nor-steroids - 19-norprogesterone (13), 19-nor-17a-ethynyltes tos terone (14) (which became the active ingredient of approximatelyfifty percent of all oral contraceptives) and the 19-norcorticosteroids (15).

Doing all this in just a couple of years would have been noticeable anywhere, but accomplishing this in Mexico City was so unexpected that this work from Syntex received international notoriety including articles in popular magazines like FORTUHE and LIFE. It also produced the first (and only) offer of an academic job a tenured associate professorship from Wayne University in Detroit.- While hardly a top university when compared to the ivy league schools, the University of California campuses or Cal Tech, Wayne University nevertheless provided a crucial stepping stone, just as it had done a few years earlier for H. C. Brown who initially had also found it difficult to secure an academic position.

In January 1952, I left sunny Mexico City and drove to cold, dirty, slushy Detroit. It proved to be the most direct route to California where I have now spent a quarter of a century.

The five years at Wayne were important - they represented my first academic job and a lot of new work was started there. My research laboratories were awful - my group was housed in the oldest building of the university and my students had to cross one of the busiest streets (four lanes, one-way traffic) to get to the stockroom. However, the stockroom was first class and generously stocked, both in terms of chemicals and glassware, and there was good IP. and UV equipment. Aside from continuing various steroid projects, my students and I started a major line of natural products chemistry in the area of antibiotics, alkaloids and terpenoids. But most importantly, shortly after my arrival at Wayne, I was able to get one of the first two spectropolarimeters constructed by the 0. C. Rudolph Company and to start a still ongoing line of research on chiroptical methods. For instrumental reasons, we commenced with optical rotatory dispersion (ORD) - the laborious manual point-by-point wavelength measurements being taken by the wives of my graduate students, notably Mrs. Riniker, Mrs. Halpern, Mrs. James and Mrs. Mitscher.

These were the days when D. H. R. Barton, and shortly W. Klyne in England had demonstrated the utility of molecular rotation differences (at a single wavelength corresponding to the sodium D line) in the steroid field and I had the intuitive feeling that measurements of optical rotation at different wavelengths (i.e..

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optical rotatory dispersion curves) would be more instructive. Luckily, I made the best possible choice for experimental substrates, namely steroid ketones. The carbonyl group proved to be the ideal chromophore with its low absorption occurring in an experimentally accessible region of the ultraviolet spectrum. The steroid frame work proved to be the ideal structural setting in which to test our intuitive hypothesis that the shape and/or sign of the ORD curve would be diagnostic for the location of the carbonyl group. Our first few papers (16) confirmed this hypothesis. More extensive measurements among steroids and related polycyclic natural products then demonstrated that it was predominantly the bicyclic environment around the carbonyl group that reflected itself in the ORD curve and we were thus able to use ORD for purposes of determination of absolute configuration. This method enabled us to report that several sesquiterpenes (18) and diterpenes (17, 19) had the "wrong" absolute configuration, i.e. the mirror image of the steroids. We then extended our measurements to ce-haloketones - a group of steroids that I had studied since my graduate school days - and made the crucial observation with W. Klyne of Westfield College, London, that an axial a-halogen substituent controlled the sign of the Cotton an observation (20) that we called the "a-ha loketone rule." Shortly it was shown to be a special case of the "octant rule" (21) which has turned out to be one of the most cited observations (22) that I have published.

I still remember the day in 1958 when I made one of my periodic visits to Harvard to my former University of Wisconsin classmate Gilbert Stork and had a long session in R. B. Woodward's office with William Moffitt and his graduate student Albert Moscowitz. Moffitt and Moscowitz had been working on theoretical aspects of optical activity and Woodward had called to their attention our experimental work and especiallyour crhalo ketone rule. In an exciting session lasting several hours, we realized that the "octant rule" represented an important extension and explainedmost of our published as well as unpublished results, and that it provided a superb and exceedingly rapid method for establishing absolute configurations. There is little doubt that work in this field would have been delayed by many years if steroids had not fortuitously been used by my group as the intial test substances.

In 1957 I took a two-year leave of absence from Wayne State University to return to Mexico City as Research Vice President of Syntex - a company for which I had consulted in the intervening five years. Syntex had just become American-owned and shortly after my return to Mexico City it became a public company with a major expansion of its research department. I brought several of my graduate students and postdoctoral fel lows with me to Mexico City, among them A. Bowers (now Chief Executive Officer of Syntex), J. Kutney (now Professor at the University of British Columbia), R. Mauli (now at Ciba-Geigy), R. Villotti (who thereafter became Italian manager of Syntex), J. S. Mills (National Gallery London), 0. Halpern (eventually Director of Process Development for Syntex), P. Crabbe (eventually Director of Chemical Research of Syntex in Mexico), and J.

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Zderic (currently Vice President, Syntex). This group, together with H. J. Ringold from the University of Washington, and a few Mexican Ph.D. chemists, notably J. Iriarte, 0. Mancera, and J. Romo under my direction carried out a series of investigations in the androgen- anabolic, corticoid, and progestational areas that in the 19505, according to L. F. Fieser, made Syntex the preeminent steroid laboratory in the world in terms of scientific publications. Among the commercially important products developed at that time by Syntex, the topical corticosteroids synthesized by my ex-Wayne group (23) proved to be the real money winner under the trade names SYNALAR and MEOSYNAIAR. Unquestionably the most important development which came to fruition during my second stay at Syntex was the FDA approval of norethindrone - synthesized in 1951 during my first Mexican sojourn - first for menstrual disorders and subsequently as an oral contraceptive. The details of that story have been published by me in a book (24) and hence need not be repeated here.

My two-year leave of absence from Wayne was supposed to end in the fall of 1959, at which time I had also completed my first book which summarized all of our ORD work (25). During those two years I travelled to Detroit every eight weeks and in addition had maintained intimate contact with all of my graduate students by long-distance telephone. In early 1959, my former University of Wisconsin professor, W. S. Johnson, asked if I would be interested in joining him if he were to move to Stanford University as the new head of its Chemistry Department. A joint visit by the two of us to Palo Alto followed by a lengthy conversation with the legendary Stanford provost F. E. Terman who promised the construction of a new laboratory building for the two of us, convinced both Johnson and me that we would accept a professorial offer from Stanford University. Officially we joined the faculty in 1959 but did not actually arrive in Palo Alto until the Stauffer Chemical Laboratory had been constructed in 1960.

In terms of steroid chemistry the 25 years at Stanford were significant ones for me pedagogical ly and scientifically. In one of my graduate courses on organic synthesis, I decided to use steroids as sole models and convinced sixteen graduate students to collaborate on a book (26) - "Steroid Reactions" - which covered exhaustively in up- to-date fashion a variety of organic chemical transformations with several thousand literature references. The information was easily digestible, because of the liberal use of structural and was used for years until it became out-of-print.

Scientifically, my Stanford period was important because it included four new areas of research in addition to the lines started at Wayne State University. The first was an extension of our earlier ORD work to optical circular dichroism (CD). Here again, we secured one of the first instruments - a prototype constructed by JASCO in Japan, which enabled us to extend our ORD work to CD of steroids and other polycyclic molecules (27) - research that was conducted at the same time by Legrand and Velluz at Roussel in Paris. Edward Bunnenberg, who had spent a year of postdoctorate work with me

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at Wayne State University, moved with ray group to Palo Alto and and since that time has been my principal colleague in the field of optical and later of magnetic circular dichroism two fields in which we" are still actively publishing. -

The second new area was organic mass spectrometry. In connection with our structural work on cactus sterols, we had realized from Reed's work in Glasgow, and the Swedish group of Ryhage and Stenhagen, that mass spectrally determined molecular weights would be very important among those natural products, where microanalysis was inadequate for precise empirical formula determination. At the same time, Biemann at MIT had just begun his work on the mass spectral fragmentation mechanisms of indole alkaloids, another field in which we had been active since Wayne State days. It seemed to me very worth-while to determine whether a detailed study of the mass spectrometric behaviour of steroid ketones - the same substances used earlier by us for ORD and CD - would prove to be of structural significance, and I proposed this line of research to an Austrian postdoctorate Herbert Budzikiewicz (now Professor at the University of Cologne), who was about to join my laboratory. Already our first paper (28) convinced us that deuterium labelling of steroids would be the key to a successful solution of this problem. In the following ten years, many of my graduate students and postdoctoral fellows were active in this field and it is fair to state that insofar as mass spectral applications to steroids is concerned, our group was preeminent and laid much of the groundwork for a technique that has since become routine. Dudley H. Williams (now at Cambridge University) joined my group shortly thereafter and together with him and Budzikiewicz, I not only published two books dealing with applications of mass spectrometry to steroids (29) and other natural products (30), but also extended our conclusions from the steroid field - namely that charge localization after electron impact is a useful concept for prediction and interpretation of mass spectra - to a wide variety of organic molecules. This work was summarized in a major book (31) published by us in 1967 which has become one of my most cited scientific contributions (32). While the height of our mass spectral efforts was reached in the late 19605, our laboratory has continued to contribute to various mechanistic and stereochemical features of mass spectrometry of steroids and non-steroids alike with approximately 260 papers in this field having appeared by now from the Stanford laboratories (33). In addition, our interest in organic mass spectrometry of steroids led us to two other new research fields.

One of these was the study of chemical applications of computer artificial intelligence techniques. Edward Feigenbaum, Professor of Computer Sciences at and Joshua Lederberg, then Chairman of our Genetics Department, had begun an important collaboration in the area of computer artificial intelligence. Lederberg, because of his theoretical and experimental interest in exobiology,invited me to convert this collaboration into a triumvirate with an initial emphasis on mass spectrometry since this was likely to be a technique useful in

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determining the possible occurrence of organic molecules in outer space. Because of our extensive background in steroid mass spectrometry, some of our initial successes were demonstrated with steroids such as estrogens (34) and laid the foundation for an exceedingly fruitful and extensive collaboration over a period of a dozen or more years, culminating in an efficient computer-aided approach to structure elucidation (35).

The fourth new area of research - isolation, structure elucidation, biosynthesis, and biological function of marine sterols - again received its initial impetus from our steroid mass spectral studies and is now at its peak. If there is any area of steroid chemistry which I would have considered a "dead" one in 1970, it would clearly have been the structure elucidation of new sterols. Little did we, or anybody else, think that in the intervening years well over 150 new sterols would be isolated from marine sources which have no counterpart in terrestrial organisms (36). These encompass sterol side-chains with cyclopropane, eye lopropene, allene and acetylene functionalities in addition to extreme branching and chain elongation. Their biosynthesis is only just yielding to experimental verification and their biological role is likely to be one in membrane function (37). Indeed, our interest in the biological function of these marine sterols led my group into still another research area: an examination of the phospholipid content of these animals, notably sponges, which uncovered a whole range of novel fatty acids seemingly unique to the marine environment (38).

In a way, marine steroid chemistry has completed a circle for me encompassing over three decades and many hundreds of publications. In 1951, we synthesized the first clinically useful 19-nor steroid (norethindrone) which still remains one of the most important active ingredients in today's oral contraceptives. At that time, 19-nor steroids were only accessible by synthesis and not by isolation from a natural source. Only in the 1970s did an Italian group (39) discover that certain sponges contain almost exclusively 19-nor sterols - an observation that we extended to some other species (40). It is not inconceivable that this observation may eventuallyprove to be of practical utility (41).

My first scientific paper appeared in 1946 (2) and dealt with steroids. There is no doubt in my mind that 40 years later some paper dealing with the isolation, synthesis, biosynthesis or biological function of some steroid will include my name as one of the authors. Was it worth the effort? At age 61, I can categorically reply in the affirmative. Whether I will still feel this way 20 or 30 years from now remains to be seen. Assuming continuing publication of I volunteer now to write a postscript at that time.

REFERENCES

(1) A. L. Wilds and C. Djerassi, J. Am. Chem. Soc. . 68, 1715 (1946). (2) A. L. Wilds and C. Djerassi, J. Am. Chem. Soc. 68, 1712 (1946). (3) A. L. Wilds and C. Djerassi, J. Am. Chem. Soc. . 68, 2125 (1946).

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(4) G, G. Inhoffen and G. Ztfhlsdorff, Chem. Ber . . 74. 1911 (1941). (5) A. L. Wilds and C. Djerassi, J. Am. Chem. Soc . 68, 1862 (1946). (6) C. Djerassi and C. R. J. Am. Chem. Soc. , 69, 2404 (1947). (7) C. Djerassi, J. Am. Chem. Soc. , 71 , 1003 (1949). (8) G. Rosenkranz, 0. Mancera, J. Gatica and C. Djerassi, J. Am. Chem. Soc, 72, 4077 (1950). (9) C. Djerassi, G. Rosenkranz, J. Romo , S. Kaufmann and J. Pataki, J. Am. Chem. Soc. 72, 4534 (1950). (10) S. J. Pataki, G. Rosenkranz, J. Romo and C. Djerassi, J. Am. Chem. Soc, 72, 4531 (1950). (11) G. Rosenkranz, J. Pataki and C. Djerassi, J. Am. Chem. Soc.. 73, 4055 (1951). (12) C. Djerassi, H. J. Ringold and G. Rosenkranz, J. Am. Chem. Soc 73, 5513 (1951). (13) L. Miramontes, G. Rosenkranz and C. Djerassi, J. Am. Chem. Soc. 73 , 3540 (1951); C. Djerassi, L. Miramontes and G. Rosenkranz, J. Am. Chem. Soc. 75, 4440 (1953). (14) C. Djerassi, L. Miramontes and G. Rosenkranz, Abstracts Am. Chem. Soc Div. Med. Chem., Milwaukee, April 1952, p. 18J; C. Djerassi, L. Miramontes, G. Rosenkranz and F. J. Am. Chem. Soc, 76, 4092 (1954). (15) A. L. Miramontes, G. Rosenkranz, C. Djerassi and F. J. Am. Chem. Soc . 75, 4117 (1953); A. H. J. Ringold, G. Rosenkranz, F. G. H. Thomas and C. Djerassi, J. Am. Chem. Soc. , 76. 6210 (1954). (16) C. Djerassi, E. W. Foltz and A. E. Lippman, J. Am. Chem. Soc, 77 , 4354 (1955).; C. Djerassi, W. Closson and A. E. Lippman, J. Am. Chem. Soc, 78. 3163 (1956). (17) C. Djerassi, R. Riniker and B. Riniker, JL, Am. Chem. Soc. , 78 , 6362 (1956). (18) C. Djerassi and S. Burstein, Tetrahedron. 7. 37 (1959). (19) C. Djerassi and D. Marshall, Tetrahedron, 1, 238 (1957). (20) C. Djerassi and W. Klyne, J. Am. Chem. Soc. 79. 1506 (1957). (21) W. R. B. Woodward, A. Moscowitz, W. Klyne and C. Djerassi, J. Am. Chem. Soc , 83, 4013 (1961). (22) Current Contents (42), Oct 18, 1982, p. 22. (23) J. S. Mills, A. Bowers, C. Djerassi and H. J. Ringold, J. Am. Chem. Soc, 82, 3399 (1960); J. A. Edwards, H. J. Ringold and C. Djerassi, J. Am. Chem. Soc, 82, 2318 (1960); J. A. Zderic, H. Carpio and C. Djerassi, J. Org. Chem. . 24, 909 (1959). (24) C. Djerassi, "The Politics of Contraception", W. H. Freeman, San Francisco, 1981, pp. 227-256. (25) C. Djerassi, "Optical Rotatory Dispersion", McGraw-Hill Book Inc. , New York, 1960. (26) C. Djerassi (cd.) ,"Stero i d Reactions - An Outline for Organic Chemists", Holden-Day, Inc., San Francisco, 1963. (27) E. Bunnenberg, C. Djerassi, K. Mislow and A. Moscowitz, J. Am. Chem. Soc, 84, 2823 (1962); C. Djerassi, H. Wolf and E. Bunnenberg, J. Am. Chem. Soc. 84, 4552 (1962). (28) H. Budzikiewicz and C. Djerassi, J_;_ Am. Chem. Soc, 84, 1430 (1962). (29) H. Budzikiewicz, C. Djerassi and D. H. Williams, "Structure Elucidation of Natural Products by Mass Spectrometry. Terpenoids, Sugars." Holden-Day, Inc, San Francisco, 1964, (30) H. Budzikiewicz, C. Djerassi and D. H. Williams, "Structure

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Elucidation of Natural Froducts by Mass Spectrometry. Alkaloids." Holden-Day, Inc., San Francisco, 1964. (31) H. Budzikiewicz, C. Djerassi and D. H. Williams, "Mass Spectrometry of Organic Compounds." Holden-Day, Inc., San Francisco, 1967. (32) Current Contents (34), Aug 23, 1982, p. 18. (33) F. J. Brown and C. Djerassi, J. Org. Chem. 46, 954 (1981). (34) D. H. Smith. B. G. Buchanan, P. S. Engelmore, A. M. A. Yeo, E. A. Feigenbaum, J. Lederberg and C. Djerassi, J. Am. Chem. Soc, 94, 5962 (1972); D. H. B. G. Buchanan, R. S. Engelmore, H. Adlercreutz and C. Djerassi, J. Am. Chem. Soc, 95, 6078 (1973); D. H. Smith. B. G. Buchanan, W. C. White, E. A. Feigenbaum, J. Lederberg and C. Djerassi, Tetrahedron, 29. 3117 (1973). (35) C. Djerassi, D. H. Smith and T. H. Varkony, Naturwissenschaften, 66, 9 (1979); C. Djerassi, D. H. C. W. N. A. B. Gray, J. G. Nourse and M. R. Lindley, Pure and Appl. Chem.. 54, 2425 (1982). (36) C. Djerassi, Pure and Appl. Chem., 53, 873 (1981). (37) R. M. K. C. Tarchini and C. Djerassi, in Frontiers of Bio-Organic Chemistry and Molecular Biology (S.N. Ananchenko , cd.), Pergamon Press, 1980, pp. 211-224. (38) E. Ayanoglu, S. Popov, J. M. Kornprobst, A. Aboud-Bichara and C. Djerassi, Lipids. 18. 830 (1983) and earlier references cited therein. (39) L. Minale and G. Sodano , J. Chem. Soc. Perkin I. 1888 (1974). (40)S. Popov, R. M. K. A. Wegmann and C. Djerassi, Tetrahedron Letters. 3491 (1976); S. Popov, R. M. K. Carlson and C. Djerassi, Steroids. 41_, 537 (1983); B. V. Crist and C. Djerassi, 42, 331 (1983). (41) C. Djerassi, in: Proceedings of the Alfred Benzon Symposium 20 (P. Krogsgaard-Larsen, S. Br^gger Christensen and H. eds.), Munksgaard, Copenhagen, 1984, pp. 164-176.

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