The presence of an a-methylene-7-lactone is essential for significant cytotoxic activity among the sesquiterpene lactones. The biological activity is enhanced by the presence of certain additional ,/3-unsaturated carbonyl functions. In addition, the activity of these compounds increases with increasing lipophilicity, but does not appear to correlate with reactivity toward cysteine. Those sesquiterpenes with demonstrated in vivo antitumor activity have common features which set them apart from the majority of the sesquiterpene lactones.A number of significantly cytotoxic sesquiterpene lactones have been isolated during the course of a continuing search for antitumor agents from plant sources.3 Despite the common occurrence of cytotoxic activity and, to a lesser extent, in vivo antitumor activity, this class of compounds has not been subjected to a systematic study of structure-activity relationships. The great structural diversity of these compounds (Chart I) precluded the determination of most of the free energy parameters required for a rigorous Hansch analysis. Other complicating factors, such as solubility difficulties in solvents used for the biological assay and biological variations in the responses, have been noted previously.4 In spite of these limitations, we felt that structure-activity relationship studies of these compounds should reveal general relationships of value to any further biological study in the area of sesquiterpene lactones.Using the data available at the time, Hartwell and Abbott4 surveyed the structural variety of the cytotoxic sesquiterpene lactones and attempted a statistical treatment of the structure-activity problem. As they noted, the small number of examples available made it difficult to arrive at definitive conclusions. It was noted, however, that all the cytotoxic sesquiterpenes were lactones, of which all but one were ,/3-unsaturated, and that the

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Hydrierkatalysatoren über die Schulter geschaut: Wie wird das Wasserstoffmolekül intermediär an das Metallatom eines Carbonylkomplexes angelagert? Welche Positionen eines Substratmoleküls werden in der Folge angegriffen? Der Verlauf einer photochemischen Hydrierung [GI. (a)] ließ sich nun erstmals NMR‐spektroskopisch über Kernspinpolarisationseffekte verfolgen. M = Mo, Cr.magnified image