Synthesis of norsesterterpene rac- and ent-rhopaloic acid A

Abstract

The stereoselective synthesis of rac- and ent-rhopaloic acid A 1 has been accomplished, via successive homologation of (2E,6E)-farnesol 2 and cyclization to form a tetrahydropyran ring, together with final introduction of an α-methylene group; the asymmetric synthesis was achieved via an Evans’ asymmetric alkylation using (S)-4-benzyloxazolidin-2-one as a chiral auxiliary; the synthetic rhopaloic acid A, with a predicted absolute configuration of (2S,5R), had a specific rotation of opposite sign to that of the natural product, and therefore the configuration of natural rhopaloic acid A should be assigned as (2R,5S).

References

1. S. Ohta, M. Uno, M. Yoshimura, Y. Hiraga and S. Ikegami, Tetrahedron Lett., 1996, 37, 2265.
2. R. L. Letsinger, S. K. Chaturvedi, F. Farooqui and M. Salunkhe, J. Am. Chem. Soc., 1993, 115, 7535; W. Ding and G. A. Ellestad, J. Am. Chem. Soc., 1991, 113, 6617; U. S. Singh, R. T. Scannell, H. Au, B. J. Carter and S. M. Hecht, J. Am. Chem. Soc., 1995, 117, 12 691; S. B. Singh, D. L. Zink, J. M. Liesch, M. A. Goetz, R. G. Jenkins, M. Nallin-Omstead, K. C. Silverman, G. F. Bills, R. T. Mosley, J. B. Gibbs, G. Albers-Schonberg and R. B. Lingham, Tetrahedron, 1993, 49, 5917.
3. J. M. Muller, H. Fuhrer and J. Gruner, Helv. Chim. Acta, 1976, 2506; E. Rodriguez, B. Sanchez, P. A. Grieco, G. Majetich and T. Oguri, Phytochemistry, 1979, 18, 1741.
4. J. P. Schaefer and J. Higgins, J. Org. Chem., 1967, 32, 1607.
5. M. J. Kates and J. H. Schauble, J. Org. Chem., 1996, 61, 4164.
6. Y. Harada, M. Shibata, T. Sugiura, S. Kato and T. Shioiri, J. Org. Chem., 1987, 52, 1252.
7. W. He, E. Pinard and L. A. Paquette, Helv. Chim. Acta, 1995, 78, 391.
8. M. F. Semmelhack, J. C. Tomesch, M. Czany and S. Boettger, J. Org. Chem., 1978, 43, 1259; M. F. Semmelhack, A. Yamashita, J. C. Tomesch and K. Hirotsu, J. Am. Chem. Soc., 1978, 100, 5565.
9. N. D. Smith, P. J. Kocienski and S. D. A. Street, Synthesis, 1996, 652; A. T. F. Edmunds and W. Trueb, Tetrahedron Lett., 1997, 38, 1009.
10. D. A. Evans, T. C. Briton, J. A. Ellman and R. L. Dorow, J. Am. Chem. Soc., 1990, 112, 4011; P. P. Waid, G. A. Flynn, E. W. Huber and J. S. Saabol, Tetrahedron Lett., 1996, 37, 4091.
11. M. Tokumasu, A. Sasaoka, R. Takagi, Y. Hiraga and K. Ohkata, Chem. Commun., 1997, 875.