3100. Didemnins
Description and references
Biologically active depsipeptides extracted from a Caribbean tunicate (sea squirt) family Didemnidae, genus Trididemnum. First marine natural product to enter clinical trials as antineoplastic. The three components, didemnins A, B and C are weakly basic compds with antiviral, antitumor activity. Didemnin A is the most abundant, whereas didemnin B is generally the most active. Isoln and bioactivity: K. L. Rinehart, Jr. et al., Science 212, 933 (1981). Extraction and purification: K. L. Rinehart, Jr., EP 48149; idem, US 4493796 (1982, 1985 both to Univ. Illinois). Structure determn: K. L. Rinehart, Jr. et al., J. Am. Chem. Soc. 103, 1857 (1981). Revised structure and total synthesis: K. L. Rinehart, Jr. et al., ibid. 109, 6846 (1987). See also: U. Schmidt et al., Tetrahedron Lett. 29, 3057 (1988); eidem, ibid. 4407. Crystal structure of B: M. B. Hossain et al., Proc. Natl. Acad. Sci. USA 85, 4118 (1988). Efficient total synthesis of A and B: Y. Hamada et al., J. Am. Chem. Soc. 111, 669 (1989). Mechanism of action study: L. H. Li et al., Cancer Lett. 23, 279 (1984). In vitro and in vivo immunosuppressive activity of B: D. W. Montgomery, C. F. Zukowski, Transplantation 40, 49 (1985). HPLC determn in biological fluids: J. N. Hartshorn et al., J. Liq. Chromatogr. 9, 1489 (1986). Clinical pharmacology, pharmacokinetics: F. A. Dorr et al., Eur. J. Cancer Clin. Oncol. 24, 1699 (1988). Review of bioactivity of A and B: K. L. Rinehart, Jr. et al., Fed. Proc. 42, 87-90 (1983); of activity and toxicology of B: H. G. Chun et al., Invest. New Drugs 4, 279-284 (1986); of biological activity, structure and synthesis: W.-R. Li, M. M. Joullie, Stud. Nat. Prod. Chem. 10, 241-302 (1992).
