Cinachyrolide A Cytotoxic Marine Macrolides yrtin A (Spongistain-4) ⊙ The)of tent.pb ally active comp Ecteinascidin 743 y 肉瘤5p2007,T746 31 N. Fusetani, K. Shinoda, S. Matsunaga, J. Am. Chem. Soc. 1993, 115, 3977-3981. Fusetani Group O O O Me OH O O O OH HO O O HO Me O HO H OH AcO HO OMe H H H HO H H H Cl 3 2 4 5 6 7 8 9 10 11 15 17 19 21 25 27 33 35 37 41 43 47 51 1 Cinachyrtin A (Spongistatin-4) Cinachyrolide A 32 Cytotoxic Marine Macrolides 33 The achievement (1993) of the three groups is especially noteworthy, since only trace amounts (0.5-13.8 mg) of these extremely potent, physiologically active compounds could be isolated for extensive NMR experiments after laborious extractions and multiple chromatographic purifications. Evans D.N. Tetrahedron 1999, 55, 8671-8726. 34 35 v含有N原子的大环内酯环 v如 ET-743 and PT-650 In phase II & III v被囊动物红树海鞘 Ecteinascidia turbineta N NH N S O O H3C O O H3C H H OH HO CH3 O O O HO O H3C H3C CH3 H Rinehart K L Antitumor activity from the Ascidian (Tunicate) Ecteinascidia turbinata (被囊动物红树海鞘 ) had been reported as early as 1969 by Sigel et al., but it was not until 1990 that the structures of the active components were published simultaneously by Rinehart et al. and Wright et al. 36 Ecteinascidin 743 • Et 743 对晚期软组织癌症如直肠癌，乳腺癌，肺癌，黑色素瘤等有显 著的疗效。Eur & USA II & III • In Europe Used to soft-tissue sarcoma (肉瘤) by Sep. 2007. ET-743 represents the first active agent against sarcomas developed in the past 25 years and has demonstrated a therapeutic potential in pretreated ovarian cancer. 1969 Found Activity 1990 Structure Deter In Illinois Uni. 1996 Total Syn. In Harvard Uni. Corey N NH N S O O H3C O O H3C H H OH HO CH3 O O O HO O H3C H3C CH3 H