, Volume 38, Issue 11, pp 1259-1275

Chemical studies on slow reacting substances/leukotrienes

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The family of eicasanoids, biologically active metabolites of polyunsaturated C20 fatty acids such as arachidonic acid, has recently been enlarged by the recognition of a new biosynthetic pathway leading to the leukotrienes, including the compounds described two decades ago as ‘slow reacting substances’. These biologically potent substances are involved in regulation of the immune response and also as mediators in various disease states. This account presents a brief history of this field, an overview of the biological relevance of leukotrienes, and a discussion of the investigations which led to the clarification of the molecular structures, pathway of biosynthesis and total chemical synthesis of the leukotrienes, including leukotrienes A, B, C, D and E (LTA-LET). As a result of the synthetic work these rare substances are available for the first time in pure form and in quantities sufficient for biological and medical studies. Also reviewed are recent discoveries with regard to the development of inhibitors of leukotriene biosynthesis and anti-leukotrienes.

20th Paul Karrer lecture, presented June 16, 1982 at the University of Zürich, Switzerland.
Acknowledgment. It is a pleasure to express admiration, appreciation, and gratitude to each of the collaborators whose names appear in the references to this article. The research has yielded great personal satisfaction as well as scientific excitement.-We are grateful to the U.S. National Science Foundation and the National Institutes of Health for financial support of the research program on leukotrienes at Harvard.