Research on the isolation and structure determination of biologically active natural products is proposed. The major emphasis will be on precisely defining the three-dimensional molecular structures of polyether macrolides, antitumor antibiotics, and heteropeptides by single crystal X-ray diffraction techniques. Specific projects described in the proposal include: 1. Compounds related to scytophycin such as tolytoxin, swinholide A, kabiramide, ulapualide, and halichondramide. 2. Antitumor antitiotics in the esperamicin and neocarzinostatin families. 3. Heteropeptides such as the theonellapeptolides, PD 124966, ulicyclamides, and didemnins. The molecular structure information obtained from this research will be of direct benefit to chemistry, biochemistry, and pharmacology. Several of the research targets could become useful drugs for the treatment of human diseases. The esperamicin antitumor antibiotics are especially promising as chemotherapeutic agents.