View PDF Version
 
DOI: 10.1039/A708187A (Paper) Reference Section for: J. Chem. Soc., Perkin Trans. 1, 1998, 1283-1294

Towards the synthesis of the squalestatins/zaragozic acids: Synthesis of an advanced intermediate and introduction of the C-1 sidechain

(Note: The full text of this document is currently only available in the PDF Version )

Robert K. Mann, Jack G. Parsons and Mark A. Rizzacasa

Abstract

A highly convergent synthesis of a squalestatin/zaragozic acid A C-4-decarboxydeoxy intermediate has been achieved. The key step involves the construction of the C-1–C-1′ bond by the addition of a fully functionalized C-1 sidechain anion (derived from iodide 34) to a bicyclic core precursor lactone 24 which provides the lactols 35. Mild acid-induced deprotection and ring closure gives the 2,8-dioxabicyclo[3.2.1]octane 36 as a 3∶1 mixture of C-3 epimers. Two-step oxidation of the C-3 alcohol to the acid followed by esterification then gives the ester 37 as the only diastereoisomer. The C-1 sidechain 34 has been synthesized in 11 steps from butane-1,4-diol while lactone 24 has been synthesized in 13 steps from the D-mannose-derived alcohol 14.

References

  1. P. J. Sidebottom, R. M. Highcock, S. J. Lane, P. A. Procopiou and N. S. Watson, J. Antibiot., 1992, 45, 648 CAS.
  2. J. D. Bergstrom, M. M. Kurtz, D. J. Rew, A. M. Amend, J. D. Karkas, R. G. Bostedor, V. S. Bansal, C. Dufresne, F. L. VanMiddlesworth, O. D. Hensens, J. M. Liesch, D. L. Zink, K. E. Wilson, J. Onishi, J. A. Milligan, G. Bills, L. Kaplan, M. Nallin Omstead, R. G. Jenkins, L. Huang, M. S. Meinz, L. Quinn, R. W. Burg, Y. L. Kong, S. Mochales, M. Mojena, I. Martin, F. Pelaez, M. T. Diez and A. W. Alberts, Proc. Natl. Acad. Sci. USA, 1993, 90, 80 CAS; K. E. Wilson, R. M. Burk, T. Biftu, R. G. Ball and K. Hoogsteen, J. Org. Chem., 1992, 57, 7151 CrossRef CAS.
  3. A. Baxter, B. J. Fitzgerald, J. L. Hutson, A. D. McCarthy, J. M. Motteram, B. C. Ross, M. Sapra, M. A. Snowden, N. S. Watson, R. J. Williams and C. Wright, J. Biol. Chem., 1992, 267, 11 705 CAS.
  4. C. D. Poulter and H. C. Rilling, in Biosynthesis of Isoprenoid Compounds, ed. J. W. Porter and S. L. Spurgeon, Wiley, New York, 1981, vol. 1, p. 414 Search PubMed.
  5. For a review on the chemistry and biology of the zaragozic acids/squalestatins see A. Nadin and K. C. Nicolaou, Angew. Chem., Int. Ed. Engl., 1996, 35, 1622 Search PubMed.
  6. (a) H. Abdel-Rahman, J. P. Adams, A. L. Boyes, M. J. Kelly, D. J. Mansfield, P. A. Procopiou, S. M. Roberts, D. H. Slee, P. J. Sidebottom, V. Sik and N. S. Watson, J. Chem. Soc., Chem. Commun., 1993, 1841 RSC; (b) V. K. Aggarwal, M. F. Wang and A. Zaparucha, J. Chem. Soc., Chem. Commun., 1994, 87 RSC; (c) L. M. McVinish and M. A. Rizzacasa, Tetrahedron Lett., 1994, 35, 923 CrossRef CAS; (d) M. K. Gurjar, S. K. Das and U. K. Saha, Tetrahedron Lett., 1994, 35, 2241 CrossRef CAS; (e) H. Koyama, R. G. Ball and G. D. Berger, Tetrahedron Lett., 1994, 35, 9185 CrossRef CAS; (f) M. K. Gurjar, S. K. Das and K. S. Sadalapure, Tetrahedron Lett., 1995, 36, 1933 CrossRef CAS; (g) M. K. Gurjar, S. K. Das and K. S. Kunwar, Tetrahedron Lett., 1995, 36, 1937 CrossRef CAS; (h) G. A. Kraus and H. Maeda, J. Org. Chem., 1995, 60, 2 CrossRef CAS; (i) S. Caron, A. I. McDonald and C. H. Heathcock, J. Org. Chem., 1995, 60, 2780 CrossRef CAS; (j) R. H. Schlessinger, X.-H. Wu and T. R. R. Pettus, Synlett, 1995, 536 CrossRef CAS; (k) A. Armstrong and P. A. Barsanti, Synlett, 1995, 903 CrossRef CAS; (l) N. Maezaki, H. J. M. Gijsen, L.-Q. Sun and L. A. Paquette, J. Org. Chem., 1996, 61, 6685 CrossRef CAS; (m) K. D. Freeman-Cook and R. L. Halcomb, Tetrahedron Lett., 1996, 37, 4883 CrossRef CAS; (n) I. Paterson, K. Feβner, M. R. V. Finlay and M. F. Jacobs, Tetrahedron Lett., 1996, 37, 8803 CrossRef CAS; (o) Y. Xu and C. R. Johnson, Tetrahedron Lett., 1997, 38, 1117 CrossRef CAS; (p) I. Paterson, K. Feβner and M. R. V. Finlay, Tetrahedron Lett., 1997, 38, 4301 CrossRef CAS; (q) S. G. Hegde and D. C. Myles, Tetrahedron Lett., 1997, 38, 4329 CrossRef CAS.
  7. E. M. Carreira and J. Du Bois, J. Am. Chem. Soc., (a) 1994, 116, 10 825; (b) 1995, 117, 8106 Search PubMed.
  8. K. C. Nicolaou, E. W. Yue, Y. Naniwa, F. De Riccardis, A. Nadin, J. E. Leresche, S. La Greca and Z. Yang, Angew. Chem., Int. Ed. Engl., 1994, 33, 2184 Search PubMed; K. C. Nicolaou, A. Nadin, J. E. Leresche, S. La Greca, T. Tsuri, E. W. Yue and Z. Yang, Angew. Chem., Int. Ed. Engl., 1994, 33, 2187 Search PubMed; K. C. Nicolaou, A. Nadin, J. E. Leresche, E. W. Yue and S. La Greca, Angew. Chem., Int. Ed. Engl., 1994, 33, 2190 Search PubMed; K. C. Nicolaou, E. W. Yue, S. La Greca, A. Nadin, Z. Yang, J. E. Leresche, T. Tsuri, Y. Naniwa and F. De Riccardis, Chem. Eur. J., 1995, 1, 467 CAS.
  9. D. A. Evans, J. C. Barrow, J. L. Leighton, A. J. Robichaud and M. Sefkow, J. Am. Chem. Soc., 1994, 116, 12 111 CrossRef CAS.
  10. D. Stoermer, S. Caron and C. H. Heathcock, J. Org. Chem., 1996, 61, 9115 CrossRef CAS; S. Caron, D. Stoermer, A. K. Mapp and C. H. Heathcock, J. Org. Chem., 1996, 61, 9126 CrossRef CAS.
  11. H. Sato, S. Nakamura, N. Watanabe and S. Hashimoto, Synlett, 1997, 451 CAS.
  12. P. A. Procopiou and N. S. Watson, Prog. Med. Chem., 1996, 33, 331 Search PubMed.
  13. T. Biftu, J. J. Acton, G. D. Berger, J. D. Bergstrom, C. Dufresne, M. M. Kurtz, R. W. Marquis, W. H. Parsons, D. R. Rew and K. E. Wilson, J. Med. Chem., 1994, 37, 421 CrossRef CAS.
  14. C. Chan, D. Andreotti, B. Cox, B. W. Dymcock, J. L. Hutson, S. E. Keeling, A. D. McCarthy, P. A. Procopiou, B. C. Ross, M. Sareen, J. J. Scicinski, P. J. Sharratt, M. A. Snowden and N. S. Watson, J. Med. Chem., 1996, 39, 207 CrossRef CAS.
  15. P. A. Procopiou, E. J. Bailey, J. L. Huston, B. E. Kirk, P. J. Sharratt, S. J. Spooner and N. S. Watson, BioMed. Chem. Lett., 1993, 3, 2527 Search PubMed.
  16. Preliminary communication: J. G. Parsons and M. A. Rizzacasa, Tetrahedron Lett., 1994, 35, 8263 Search PubMed.
  17. R. E. Ireland and R. H. Mueller, J. Am. Chem. Soc., 1972, 94, 5897 CrossRef CAS Review: S. Pereira and M. Srebnik, Aldrichim. Acta, 1993, 26, 17 Search PubMed.
  18. R. E. Ireland and D. W. Norbeck, J. Am. Chem. Soc., 1985, 107, 3279 CrossRef CAS.
  19. R. W. Gable, L. M. McVinish and M. A. Rizzacasa, Aust. J. Chem., 1994, 47, 1537 CAS.
  20. D. D. Dhavale, E. Tagliavini, C. Trombini and A. Umani-Ronchi, J. Org. Chem., 1989, 54, 4100 CrossRef CAS.
  21. H. C. Kolb, M. S. VanNieuwenhze and K. B. Sharpless, Chem. Rev., 1994, 94, 2483 CrossRef CAS.
  22. R. E. Ireland, C. S. Wilcox and S. Thaisrivongs, J. Org. Chem., 1978, 43, 786 CrossRef CAS.
  23. K. Chow and S. Danishefsky, J. Org. Chem., 1990, 55, 4211 CrossRef CAS.
  24. E. J. Corey and J. W. Suggs, J. Org. Chem., 1973, 38, 3224 CrossRef CAS.
  25. Addition of methyllithium to the corresponding C-6, 7-bis TBDMS-protected lactone and the C-6-benzyl C-7-TBDMS lactone was less efficient: M. A. Rizzacasa and J. G. Parsons, unpublished work.
  26. P. G. McDougal, J. G. Rico, Y.-I. Ohand and B. D. Condon, J. Org. Chem., 1986, 51, 3388 CrossRef CAS.
  27. S. Takano, K. Inomota, K. Samizu, S. Tomita, M. Yanase, M. Suzuki, Y. Iwabuchi, T. Sugihara and K. Ogasawara, Chem. Lett., 1989, 1283 CAS.
  28. D. A. Evans, J. Bartroli and T. L. Shih, J. Am. Chem. Soc., 1981, 103, 2127 CrossRef CAS.
  29. J. R. Gage and D. A. Evans, Org. Synth., 1989, 68, 83.
  30. A. Basha, J. L. Lipton and S. M. Weinreb, Tetrahedron Lett., 1977, 4171 CrossRef CAS; D. A. Evans, S. L. Bender and J. Morris, J. Am. Chem. Soc., 1988, 110, 2506 CrossRef CAS.
  31. A. J. Robichaud, G. D. Berger and D. A. Evans, Tetrahedron Lett., 1993, 34, 8403 CrossRef CAS.
  32. E. J. Corey, S. G. Pyne and W. Su, Tetrahedron Lett., 1983, 24, 4883 CrossRef CAS.
  33. W. F. Bailey and E. R. Punzalen, J. Org. Chem., 1990, 55, 5404 CrossRef CAS.
  34. D. B. Dess and J. C. Martin, J. Am. Chem. Soc., 1991, 113, 7277 CrossRef CAS.
  35. B. O. Lindgren and T. Nilsson, Acta Chem. Scand., 1973, 27, 888 CrossRef CAS.
Click here to see how this site uses Cookies. View our privacy policy here.