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Alkaloid Chemistry: the Work of Walter A. Jacobs

Open AccessPublished:September 20, 2002DOI:https://doi.org/10.1016/S0021-9258(18)36825-X
      The Ergot Alkaloids. II. The Degradation of Ergotinine with Alkali. Lysergic Acid
 (Jacobs, W. A., and Craig, L. C. (1934) J. Biol. Chem. 104, 547–551)
      Walter Abraham Jacobs (1883–1967) was born in New York City and after a public school education, attended Columbia University from which he received both A. B. (1904) and A. M. (1905) degrees in chemistry. He enrolled in the University of Berlin and received the Ph.D. degree in 1907 for work done with Emil Fischer. He returned to New York and a position as a fellow in chemistry with Phoebus A. Levene, the author of a previous Journal of Biological Chemistry (JBC) Classic (
      • JBC Classics
      • Levene P.A.
      ), at the newly founded Rockefeller Institute for Medical Research, later Rockefeller University. Levene was a preeminent natural product chemist, and Jacobs worked with him for several years particularly on the chemistry of nucleic acids (
      • Elderfield R.C.
      ). In 1912, Jacobs was promoted to Associate Member of the Institute and given independent status. The Institute Director, Simon B. Flexner, felt that chemotherapy deserved a division of its own, and Jacobs was made the head.
      He was joined by Michael Heidelberger, author of another JBC Classic (
      • JBC Classics
      • Heidelberger M.
      • Goebel W.F.
      ), in a remarkably productive collaboration. Their first project, the synthesis of drugs to treat poliomyelitis, failed. When they turned their attention to drugs to treat African sleeping sickness, trypanosomiasis, however, the effort was successful. With the synthesis of Tryparsimide, paraphenylglycine amide arsonate, they created a drug for the disease, more effective than anything then available. Their work was widely recognized, and some years later, in 1953, Jacobs and Heidelberger and their collaborators were made Officers of the Order of Leopold II by the Belgian government. The Jacobs-Heidelberger team later worked on other problems including attempts to synthesize anti-pneumococcal and -streptococcal drugs albeit with only modest sucesss. After nine years with Jacobs, Heidelberger went to work with Donald D. Van Slyke at the Rockefeller, also the author of a JBC Classic (
      • JBC Classics
      • Van Slyke D.D.
      • Neill J.M.
      ), to learn biochemistry. Heidelberger began his independent career at Columbia University where he became a pioneer and later legendary immunochemist (
      • JBC Classics
      • Heidelberger M.
      • Goebel W.F.
      ). Jacobs was appointed a Full Member at the Rockefeller Institute and began to investigate the structures of physiologically active natural products, especially alkaloids.
      He first explored the structures of several cardiac glycosides from digitalis and strophanthidin and ultimately determined many complex structures. In 1932, Jacobs began a period of intense study of the ergot alkaloids with Lyman C. Craig, the author of a future JBC Classic and co-author of the JBC Classic reprinted here. (Jacobs and Craig published more than 50 papers together during the period of a decade.) Ergot is the product of a fungus that grows on rye plants. Its effects on pregnancy have been known for more than 2000 years, and it was used by physicians to induce abortion 400 years ago. In addition, the consumption of contaminated grain had resulted in many epidemics the cause of which was not recognized until 1670 (
      • Elderfield R.C.
      ). The chemistry of the ergot alkaloids was very poorly understood in 1932 when Jacobs and Craig started their work. By 1934, as reported in this JBC Classic, they had identified lysergic acid in an alkali digest of ergotinine. Subsequently they demonstrated that lysergic acid is the structural core of the ergot alkaloids. LSD, the diethyl amide of lysergic acid, was synthesized a few years later by other workers (
      • Elderfield R.C.
      ). Jacobs continued to investigate alkaloid structures, among them the aconite alkaloids, which include some of the most poisonous substances known such as the toxic heteratisine, hetisine, and benzoylheteratisine from monkshood (
      • Elderfield R.C.
      ). The last alkaloids that he studied were the complex group of veratrum alkaloids also known as the steroid bases.
      Jacobs was a very distinguished chemist and a highly respected member of the Rockefeller Institute for more than 50 years. He received many honors including election to the National Academy of Sciences in 1932. He was granted emeritus status in 1949 and retired in 1957.
      Figure thumbnail gr1
      Walter A. Jacobs. Photo courtesy of the National Library of Medicine.

      References

        • JBC Classics
        • Levene P.A.
        J. Biol. Chem. 1919; 40 (http://www.jbc.org/cgi/content/full/277/22/e11): 415-424
        • Elderfield R.C.
        Biographical Memoir for Walter Abraham Jacobs. 51. National Academy of Sciences, Washington, D. C.1980: 247-278
        • JBC Classics
        • Heidelberger M.
        • Goebel W.F.
        J. Biol. Chem. 1926; 70 (http://www.jbc.org/cgi/content/full/277/36/e24): 613-624
        • JBC Classics
        • Van Slyke D.D.
        • Neill J.M.
        J. Biol. Chem. 1924; 61 (http://www.jbc.org/cgi/content/full/277/27/e16): 523-543