An improved synthesis of the ABC ring model of ecteinascidins

Heterocycles

Volumn 51, Issue 1, 1999, Pages 9-12

  Saito, Naoki ^a   Kamayachi, Hiroshi ^a   Tachi, Masashi ^a   Kubo, Akinori ^a  

^a MEIJI PHARMACEUTICAL UNIVERSITY   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

1,2,3,4,5,6 HEXAHYDRO 1,5 IMINO 9 METHOXY 3,8,11 TRIMETHYL 4 OXO 3 BENZAZOCINE; ANTINEOPLASTIC AGENT; ECTEINASCIDIN; TETRAHYDROISOQUINOLINE DERIVATIVE; UNCLASSIFIED DRUG;

ANTINEOPLASTIC ACTIVITY; ARTICLE; CARIBBEAN ISLANDS; DRUG ISOLATION; DRUG STRUCTURE; DRUG SYNTHESIS; NONHUMAN; PROTON NUCLEAR MAGNETIC RESONANCE;

EID: 0032838966     PISSN: 03855414     EISSN: None     Source Type: Journal    
DOI: 10.3987/com-98-8358     Document Type: Article

References (12)

1. R. Sakai, E. A. Jares-Erijiman, I. Manzanares, M. V. S. Elipe, and K. L. Rinehart, J. Am. Chem. Soc., 1996, 118, 9017 and references therein. For previous work on the synthesis of the ecteinascidins, see: E. J. Corey and D. Y. Gin, Tetrahedron Lett., 1996, 37, 7163; N. Saito, K. Tashiro, Y. Maru, K. Yamaguchi, and A. Kubo, J. Chem. Soc., Perkin Trans, 1, 1997, 53.
2. R. Sakai, E. A. Jares-Erijiman, I. Manzanares, M. V. S. Elipe, and K. L. Rinehart, J. Am. Chem. Soc., 1996, 118, 9017 and references therein. For previous work on the synthesis of the ecteinascidins, see: E. J. Corey and D. Y. Gin, Tetrahedron Lett., 1996, 37, 7163; N. Saito, K. Tashiro, Y. Maru, K. Yamaguchi, and A. Kubo, J. Chem. Soc., Perkin Trans, 1, 1997, 53.
3. R. Sakai, E. A. Jares-Erijiman, I. Manzanares, M. V. S. Elipe, and K. L. Rinehart, J. Am. Chem. Soc., 1996, 118, 9017 and references therein. For previous work on the synthesis of the ecteinascidins, see: E. J. Corey and D. Y. Gin, Tetrahedron Lett., 1996, 37, 7163; N. Saito, K. Tashiro, Y. Maru, K. Yamaguchi, and A. Kubo, J. Chem. Soc., Perkin Trans, 1, 1997, 53.
4. For previous work on the synthesis of the saframycins, see: A, Kubo and N. Saito, 'Synthesis of Isoquinolinequinone Antibiotics', in Studies in Natural Products Chemistry, Vol. 10, ed. by Atta-ur-Rahman, Elsevier, Amsterdam, 1992, pp. 77-145. An elegant total synthesis of ecteinascidin 743 was recently reported; E. J. Corey, D. Y. Gin, and R. S. Kania, J. Am. Chem. Soc., 1996, 118, 9202.
5. For previous work on the synthesis of the saframycins, see: A, Kubo and N. Saito, 'Synthesis of Isoquinolinequinone Antibiotics', in Studies in Natural Products Chemistry, Vol. 10, ed. by Atta-ur-Rahman, Elsevier, Amsterdam, 1992, pp. 77-145. An elegant total synthesis of ecteinascidin 743 was recently reported; E. J. Corey, D. Y. Gin, and R. S. Kania, J. Am. Chem. Soc., 1996, 118, 9202.
6. a) N. Saito, Y. Obara, M. Azumaya, and A. Kubo, Chem. Pharm. Bull., 1992, 40, 2620;
7. b) N. Saito, Y. Obara, T. Aihara, S. Harada, Y. Shida, and A. Kubo, Tetrahedron, 1994, 50, 3915.
8. 13C-NMR, IR, and MS. The molecular composition of the compounds was determined by elemental analysis or HRMS.
9. 2O (30%); TfOH (38%); CSA (25%).
10. For a closely similar, successful cyclization using a brominated compound in total synthesis of (±)-quinocarcin, see: T. Fukuyama and J. J. Nunes, J. Am. Chem. Soc., 1988, 110, 5196.
11. 1H NMR spectra of 19, when H-7 (δ 6.63) was irradiated, nOe (8.3%) of the methyl protons at δ 2.25 was observed. On the other hand, this nOe was negligible in the spectra of 12. These results indicated that 12 was a para-brominated compound and 19 was an ortho-brominated compound.
12. As a preliminary experiment, debenzylation of 13 in TFA gave 16 (52%) and 17 (31%). Treatment of 13 with trimethylsilyl iodide (1.5 eq) in chloroform at 50°C for 24 h gave 16 (18%) and 21 (mp 206-208°C; 28%); see: E. H. Vickery, L. F. Pahler, and E. J. Eisenbraun, J. Org. Chem., 1979, 44, 2444.