Nicolaou K C, Smith A L, Yue E W
Department of Chemistry, Scripps Research Institute, La Jolla, CA 92037.
Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):5881-8. doi: 10.1073/pnas.90.13.5881.
Ever since the initial reports of the enediyne anticancer antibiotics in the late 1980s, researchers from a number of disciplines have been devoting increasing attention to their chemistry, biology, and potential medical applications. Synthetic chemists and molecular designers have been engaged in attempts to synthesize these molecules and to model their unique architecture. Considerable efforts have been directed at understanding and mimicking the various processes involved in the targeting, activation, and DNA cleavage associated with these natural products. This review summarizes the main contributions to the field, with particular emphasis on work from our laboratories. Highlights include studies of the Bergman reaction, which is central to the mechanism of action of enediynes, the design and chemical synthesis of a number of these systems, and biological studies with selected molecules. Finally, the total synthesis of calicheamicin gamma 1I, the most prominent member of this class of naturally occurring compounds, is discussed.
