Total synthesis of hydroxymethylacylfulvene, an antitumour derivative of illudin S

Abstract

(±)-Hydroxymethylacylfulvene is synthesized in 14 steps from 4-hydroxy-5-methyl-2-cyclopenten-1-one and 1-acetyl-1-(diazoacetyl)cyclopropane in 15% overall yield.

References

1. T. C. McMorris, M. J. Kelner, W. Wang, M. A. Diaz, L. A. Estes and R. Taetle, Experientia, 1996, 52, 75.
2. T. C. McMorris, M. J. Kelner, W. Wang, J. Yu, L. A. Estes and R. Taetle, J. Nat. Prod., 1996, 59, 896.
3. T. C. McMorris and M. Anchel, J. Am. Chem. Soc., 1965, 87, 1594.
4. T. C. McMorris, M. J. Kelner, W. Wang, L. A. Estes, M. A. Montoya and R. Taetle, J. Org. Chem., 1992, 57, 6876.
5. M. J. Kelner, T. C. McMorris and R. Taetle, Anticancer Res., 1995, 15, 873.
6. M. J. Kelner, T. C. McMorris, L. A. Estes, M. A. Montoya, R. Starr, K. Samson and R. Taetle, Cancer Res., 1995, 55, 4936.
7. M. J. Kelner, T. C. McMorris, L. A. Estes, W. Wang, K. M. Samson and R. Taetle, Investigational New Drugs, 1996, 14, 161.
8. Unpublished data provided by MGI Pharma Inc., Minneapolis. This company has been licensed by the University of California to develop illudin analogues for treating tumours. U.S. Patents 5,439,936, 5,439,942, 5,523,490 and 5,563,176 on these compounds have been issued to the University of California, and several more are pending.
9. G. Piancatelli, A. Scettri and S. Barbadoro, Tetrahedron Lett., 1976, 39, 3555.
10. A. Padwa, E. A. Curtis and V. P. Sandanayaka, J. Org. Chem., 1996, 61, 73.
11. F. R. Kinder and K. W. Bair, J. Org. Chem., 1994, 59, 6965.
12. M. Kitamura, M. Isobe, Y. Ichikawa and T. Goto, J. Am. Chem. Soc., 1984, 106, 3252.
13. P. Camps, J. Cardellach, J. Font, R. M. Ortuno and O. Ponsati, Tetrahedron, 1982, 38, 2395.
14. D. B. Dess and J. C. Martin, J. Am. Chem. Soc., 1991, 113, 7277; R. E. Ireland and L. Liu, J. Org. Chem., 1993, 58, 2899.