Description and references

Novel tetracyclic diterpene antibiotic with antiviral and antimitotic properties, isolated as (+)-form from Cephalosporium aphidicola Petch. Specific inhibitor of DNA α-polymerase. Description and x-ray crystallographic determn of structure: K. M. Brundret et al., Chem. Commun. 1972, 1027. Prepn and antiviral activity: A. Borrow et al., US 3761512 (1973 to ICI). Structure and abs config: W. Dalziel et al., J. Chem. Soc. Perkin Trans. 1 1973, 2841. Total synthesis of (±)-aphidicolin: B. M. Trost et al., J. Am. Chem. Soc. 101, 1328 (1979); J. E. McMurry et al., ibid. 1331; E. J. Corey et al., ibid. 102, 1743 (1980); J. E. McMurry et al., Tetrahedron 37, Suppl. 1, 319 (1981). Antiviral effects in vitro and in vivo: R. A. Bucknall et al., Antimicrob. Agents Chemother. 4, 294 (1973). Antimitotic activity: S. Ikegami et al., Nature 275, 458 (1978). Effects on DNA synthesis in mouse sarcoma: S. Seki et al., Biochim. Biophys. Acta 610, 413 (1980). Enzymatic determn method: G. Pedrali-Noy et al., J. Biochem. Biophys. Methods 4, 113 (1981). Induction of differentiation of human myeloid leukemia cells: J. Griffin et al., Exp. Hematol. 10, 774 (1982). Effects on cell proliferation: G. Iliakis et al., Int. J. Radiat. Biol. 42, 417 (1982); on γ-irradiated human fibroblasts: P. J. Smith, M. C. Paterson, Biochim. Biophys. Acta 739, 17 (1983).

Properties

Derivative