Synthesis of various model compounds for the central tricyclic ring system of popolophuanone E

Tetrahedron Letters

Volumn 37, Issue 32, 1996, Pages 5719-5722

  Ueki, Yasuyuki ^a   Itoh, Masanori ^a   Katoh, Tadashi ^a   Terashima, Shiro ^a  

^a SAGAMI CHEMICAL RESEARCH CENTER   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

CYTOTOXIC AGENT; POPULOPHUANONE E; UNCLASSIFIED DRUG;

ARTICLE; DRUG STRUCTURE; DRUG SYNTHESIS; REACTION ANALYSIS; STEREOCHEMISTRY;

EID: 0030570859     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/0040-4039(96)01209-9     Document Type: Article

References (19)

1. 2. Carney, J. R., Scheuer, P. J., Tetrahedron Lett., 1993, 34, 3727-3730.
2. 2
3. 4. Quite recently, Wiemer et al. reported the first total synthesis of racemic 2, see, Watson, A. T., Park, K., Wiemer, D. F., Scott, W. J., J. Org. Chem., 1995, 60, 5102-5106.
4. 2
5. 6. To our best knowledge, there have been no reports on the synthesis of these compounds.
6. 7. Rashid, A., Read, G., J. Chem. Soc. (C), 1967, 1323-1325.
7. 8. Lübbecke, H., Boldt, P., Tetrahedron, 1978, 34, 1577-1579.
8. 9. In order to directly obtain the requisite cyclization product 9a, the annulation of 5a with 7 was examined under a variety of reaction conditions. However, only the coupling product 8a was produced as an isolable product instead of 9a.
9. 10. The electron-donating methoxy group present at the C-3 position in 5a plays an important role in this coupling reaction to afford the C-substituted product 8a. If 4-methoxyphenol was employed for the coupling reaction with 7 instead of 5a, the corresponding O-substituted product was produced as a single isomer in 48% yield.
10. 11. To be published in a separate paper.
11. 12. When 8a was treated with other bases such as LiHMDS, NaH, KH, Et3N, pyridine, DBU, K2CO3, Cs2CO3, etc., 9a was generated in poor yields (< 20%).
12. 13. A number of attempts to achieve the full deprotection of 9a in one step to complete the synthesis of 4a resulted in failure.
13. 2
14. 15. Winkle, M. R., Ronald, R. C., J. Org. Chem., 1982, 47, 2101-2108.
15. 16. The cis-fused decalin aldehyde iv was prepared as an inseparable mixture of epimers from the optically pure (-)-Wieland-Miescher ketone i as shown below. The epimers could be readily separated after the coupling with the aromatic portion 12 or 16. The conversion of i to the cis-fused decalin ii was carried out according to the reported procedures, see, a) Corey, E. J., Ohno, M., Mitra, R. B., Vatakencherry, P. A., J. Am. Chem. Soc., 1964, 86, 478-485.
16. b) McMurry, J. E., ibid., 1968, 90, 6821-6825. (formula presented)
17. 17. Wakamatsu, T., Nishi, T., Ohnuma, T., Ban, Y., Syn. Commun., 1984, 14, 1167-1173.
18. 18. Shi, S., Katz, T. J., Yang, B. V., Liu, L., J. Org. Chem., 1995, 60, 1285-1297.
19. 19. In vitro cytotoxicity of 4a-e as well as their synthetic intermediates (8a,b, 9a,b, 10a,b, 21c-e, 22c-e, and 23c,d) against murine leukemia cell ( P388 ), human leukemia cells ( CEM and HSB2 ), and human non-small cell lung cancer cells ( A549 and QG56 ) will be reported in a full account along with their inhibitory activity against topoisomerase-II.