An efficient protocol for the synthesis of unsymmetrical pyrazines. Total synthesis of dihydrocephalostatin 1

Journal of the American Chemical Society

Volumn 118, Issue 43, 1996, Pages 10672-10673

  Guo, Chuangxing ^a   Bhandaru, Sudhakar ^a   Fuchs, P L ^a   Boyd, Michael R ^b  

^a PURDUE UNIVERSITY   (United States)

^b NATIONAL CANCER INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYTOTOXIC AGENT; PYRAZINE DERIVATIVE; STEROID;

ARTICLE; DRUG SYNTHESIS; REACTION ANALYSIS; STEREOCHEMISTRY; TECHNIQUE;

EID: 0029822350     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja962646q     Document Type: Article

References (22)

1. Cephalostatin synthesis 10. For additional syntheses of cephalostatin-related pyrazines, see: (a) Pan, Y.; Merriman, R. L.; Tanzer, L. R.; Fuchs, P. L. Bioorg. Med. Chem. Lett. 1992, 2, 967. (b) Kramer, A.; Ullmann, U.; Winterfeldt, E. J. Chem. Soc., Perkin Trans. 1 1993, 2865. Reference 6.
2. Cephalostatin synthesis 10. For additional syntheses of cephalostatin-related pyrazines, see: (a) Pan, Y.; Merriman, R. L.; Tanzer, L. R.; Fuchs, P. L. Bioorg. Med. Chem. Lett. 1992, 2, 967. (b) Kramer, A.; Ullmann, U.; Winterfeldt, E. J. Chem. Soc., Perkin Trans. 1 1993, 2865. Reference 6.
3. Cephalostatin synthesis 10. For additional syntheses of cephalostatin-related pyrazines, see: (a) Pan, Y.; Merriman, R. L.; Tanzer, L. R.; Fuchs, P. L. Bioorg. Med. Chem. Lett. 1992, 2, 967. (b) Kramer, A.; Ullmann, U.; Winterfeldt, E. J. Chem. Soc., Perkin Trans. 1 1993, 2865. (c) Reference 6.
4. Pettit, G. R.; Inoue, M.; Kamano, Y.; Herald, D. L.; Arm, C.; Dufresne, C.; Christie, N. D.; Schmidt, J. M.; Doubek, D. L.; Krupa, T. S. J. Am. Chem. Soc. 1988, 110, 2006.
5. (a) Pettit, G. R.; Xu, J.; Schmidt, J. M.; Boyd, M. R. Bioorg. Med. Chem. Lett. 1995, 5, 2027 and references cited therein.
6. (b) Fukuzawa, S.; Matsunaga, S.; Fusetani, N. Tetrahedron 1995, 51, 6707 and references cited therein.
7. Pettit reports that ∼0.5 ton of the organisms yielded approximately 100 mg of cephalostatin 1 (1); ∼1 g of material is required for the initial phases of the trials. Professor G. R. Pettit, personal communication, 1994.
8. Jeong, J. U.; Sutton, S. C.; Kim, S.; Fuchs, P. L. J. Am. Chem. Soc. 1995, 117, 10157.
9. (a) Smith, S. C.; Heathcock, C. H. J. Org. Chem. 1992, 57, 6379.
10. (b) Heathcock, C. H.; Smith, S. C. J. Org. Chem. 1994, 59, 6828.
11. It should be noted that many varients of the mechanism are possible and one shown by the Purdue group simply represents a working hypothesis inspired by the Weinreb pyridine synthesis. (a) Subramanyam, C.; Noguchi, M.; Weinreb, S. M. J. Org. Chem. 1989, 54, 5580. (b) Levin, J. I.; Weinreb, S. M. J. Org. Chem. 1984, 49, 4325.
12. It should be noted that many varients of the mechanism are possible and one shown by the Purdue group simply represents a working hypothesis inspired by the Weinreb pyridine synthesis. (a) Subramanyam, C.; Noguchi, M.; Weinreb, S. M. J. Org. Chem. 1989, 54, 5580. (b) Levin, J. I.; Weinreb, S. M. J. Org. Chem. 1984, 49, 4325.
13. (a) Li, C.; Arasappan, A.; Fuchs, P. L. Tetrahedron Lett. 1993, 34, 3535.
14. (b) Li, C.; Shih, T.-L.; Jeong, J. U.; Arasappan, A.; Fuchs, P. L. Tetrahedron Lett. 1994, 35, 2645.
15. Dibutyltin dichloride is known to promote imine formation: Stetin, C.; de Jeso, B.; Pommier, J. C. Synth. Commun. 1982, 12, 495.
16. Bhandaru, S.; Fuchs, P. L. Tetrahedron Lett. 1995, 36, 8351.
17. In the synthesis of 2, we elected to employ PVP as the additive since the north and south spiroketals are sensitive to acid.
18. D = +80° (c 0.04, MeOH); see Supporting Information for spectra.
19. Boyd, M. R. In Current Therapy in Oncology; Neiderhuber, J. E., Ed.; B. C. Decker: Philadelphia, PA, 1993; pp 11-22.
20. Boyd, M. R.; Paull, K. D. Drug Dev. Res. 1995, 34, 91.
21. Pettit, G. R.; Xu, J.; Williams, M. D.; Christie, N. D.; Doubek, D. L.; Schmidt, J. M.; Boyd, M. R. J. Nat. Prod. 1994, 57, 52.
22. Bhandaru, S.; Fuchs, P. L. Tetrahedron Lett. 1995, 36, 8347.