THE ISOLATION AND STRUCTURAL CHARACTERIZATION OF THE ECTEINASCIDINS (MARINE, TUNICATE, ANTITUMOR)

The bio-assay directed isolation and structural characterization of a series of related novel compounds from the caribbean tunicate, Ecteinascidia turbinata is described. The isolation was followed using assays for in vitro antimicrobial activity, in vitro cytotoxicity, and in vivo antitumor activity. A new technique silica gel thin laver chromatography (TLC) bioautography was developed to help direct the isolation. The bioactive compounds in E. turbinata are unstable and especially sensitive to oxidation. The isolation minimized decomposition by exploiting gentle isolation techniques such as counter-current chromatography. Six novel compounds were isolated in 10('-4) to 10('-5)% yield with a total recovery of bioactivity near 60%. Two of the compounds have potent in vivo antitumor activity which accounts for the antitumor activity found in crude extracts.; The ecteinascidins are assigned structures of tris-tetrahydroisoquinolines. The determination of their partial structures was based on extensive use of high resolution fast atom bombardment mass spectrometry (FABMS), MS/MS, liquid chromatography FABMS (LC/FABMS), and two-dimensional nuclear magnetic resonance (NMR) correlation spectroscopy (COSY)...