3503. Ecteinascidins

Description and references

Family of tetrahydroisoquinoline alkaloids with antitumor activity isolated from the Caribbean tunicate, Ecteinascidin turbinata. Ecteinascidin 743 is the most abundant; bends DNA toward the major groove by selectively alkylating guanine from the minor groove. Prepn: K. L. Rinehart, T. G. Holt, WO 8707610; eidem, US 5089273 (1987, 1992 both to Univ. Illinois); and structures: K. L. Rinehart et al., J. Org. Chem. 55, 4512 (1990); R. Sakai et al., Proc. Natl. Acad. Sci. USA 89, 11456 (1992). Crystal structures: Y. Guan et al., J. Biomol. Struct. Dyn. 10, 793 (1993). Biosynthetic studies: R. G. Kerr, N. F. Miranda, J. Nat. Prod. 58, 1618 (1995).

Chemical structure

Derivative

Trabectedin.

Nomenclature

CAS number: 114899-77-3
(1′R,6R,6aR,7R,13S,14S,16R)-5-(Acetyloxy)-3′,4′,6,6a,7,13,14,16-octahydro-6′,8,14-trihydroxy-7′,9-dimethoxy-4,10,23-trimethylspiro[6,16-(epithiopropanoxymethano)-7,13-imino-12H-1,3-dioxolo[7,8]isoquino[3,2-b][3]benzazocine-20,1′(2′H)-isoquinolin]-19-one; ecteinascidin 743; ET-743; Yondelis (PharmaMar).
C39H43N3O11S; mol wt 761.84.
C 61.48%, H 5.69%, N 5.52%, O 23.10%, S 4.21%.

Description and references

Enantioselective total synthesis: E. J. Corey et al., J. Am. Chem. Soc. 118, 9202 (1996). In vitro antitumor activity: E. Isbicka et al., Ann. Oncol. 9, 981 (1998). HPLC determn in plasma: H. Rosing et al., J. Chromatogr. B 710, 183 (1998). Clinical pharmacokinetics: C. van Kesteren et al., Clin. Cancer Res. 6, 4725 (2000). Review of mechanism of action: G. J. Aune et al., Anti-Cancer Drugs 13, 545-555 (2002); of clinical development: C. van Kesteren et al., ibid. 14, 487-502 (2003); of metabolism and hepatotoxicity: J. H. Beumer et al., Pharmacol. Res. 51, 391-398 (2005).

Properties

[α]D25 +114° (c = 0.1 in methanol).

Therapeutic Category

Antineoplastic.

Keywords

Trabectedin: Antineoplastic; Alkaloids/Natural Products