Ecteinascidia turbinata ecteinascidins from

Pommier Y, Kohlagen G BaiUy C, Waring M, Mazumder A, Kohn K. (1996) DNA sequence- and structure-selective alkylation of guanine N2 in the DNA minor groove by ecteinascidin 743, a potent antitumor compound from the Caribbean tunicate Ecteinascidia turbinata. Biochemistry 35 13303-13309. 

Rinehart KL, Holt TG, Fiegeau NL, Stroh JG, Keifer PA, Sun F, Li LH, Martin DG (2002) Ecteinascidins 729, 743, 745, 759A, 759B, and 770 potent antitumor agents from the Caribbean tunicate Ecteinascidia turbinata. J Org Chem 55(15) 4512-4515... 

The ecteinascidins constitute a group of very complex alkaloid tris(tetrahydroisoquinolines) with potent in vivo antitumor activity and were isolated from the colonian Caribbean tunicate Ecteinascidia turbinata. The compounds are abbreviated as Et followed by a number that represents the value of the highest mass ion observed in the (+)-FABMS. Reports of the potent in vivo activity of extracts of that tunicate date back to 1969, when it was reported that such extracts gave T/C values of up to 272 vs P388, with four of six cures in one experiment, and they were also found to be powerful immunomodulators [72]. After a decade of effort, two research groups reported at the same time the structures of four [Et 743 (1), Et 729 (63), Et 745 (64), and Et 770 (66)] [72] and two [Et 743 (1), Et 729(63)] [73] ecteinascidins, respectively. The development of an isolation process that was efficient on a large scale allowed Rinehart s group to obtain additional ecteinascidins, Et 743 V2-oxide (67), Et 722... 

Ecteinascidin-743 (ET-743, 16, Figure 2.4) is a tetrahydroisoquinolone alkaloid isolated from Ecteinascidia turbinata Herdman, a tunicate that grows on mangrove roots throughout the Caribbean Sea [154]. Most likely, the compound is produced by the marine tunicate as a defense mechanism to survive in its natural environment [155]. 

Structural similarity of the compounds to known microbial products. An example of this is ecteinascidin 729 (Scheme 32), derived from the ascidian Ecteinascidia turbinata (26). This compound is stmcturally similar to the actinomycete-pro-duced saframycin a (Scheme 33) and related compounds (57)... 

Ecteinascidins, isolated mainly from the Caribbean ascidian Ecteinascidia turbinata, are probably the most usefiil anticancer agents found to date in a marine source. The lead compoimd, trabectedin (ET-743, 136), is regarded as a successful story of modem marine dmg research it is indeed the first representative of a marine natural product to receive marketing authorization for the treatment of patients with advanced or metastatic soft tissue sarcomas (STS) and relapsed platinum -sensitive ovarian cancer under the brand name Yondelis [116,117). 

Guan, Y., Sakai, R., Rinehart, K. L., Wang, A. H. J., 1993. Molecular and crystal structure s of ecteinascidins potent antitumor compounds from the Caribbean tunicate Ecteinascidia turbinata. J. Biomol Struct. Dyn. 10, 793-818. 

Ecteinascidin 743 is a marine tetrahydroisoquinoUne alkaloid that was isolated from Ecteinascidia turbinata, a mangrove tunicate, and is now approved by the FDA as an orphan dmg under the trade name Yondelis against soft tissue sarcoma and ovarian cancer [27]. Amine 53, isocyanide 54, acetaldehyde 55, and carboxylic acid 56 were heated in MeOH at 70°C to build up the dipeptide 60 in 90% yield (Scheme 6.5). 

The literature on ecteinascidins (ETs), in particular that on ET-743, is very abundant and we present here only a brief overview. Much information is available on the Internet. Almost all of the ETs currently known were isolated from the same species, Ecteinascidia turbinata. 

Figure 28.35 Structures of some ecteinascidins (from Ecteinascidia turbinata and E. tburstoai).

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