Stereocontrolled total synthesis of (+)-leucascandrolide A

Angewandte Chemie - International Edition

Volumn 42, Issue 3, 2003, Pages 343-347

  Paterson, Ian ^a   Tudge, Matthew ^a  

^a UNIVERSITY OF CAMBRIDGE   (United Kingdom)

Author keywords

Aldol reaction; Antitumor agents; Macrolides; Natural products; Total synthesis

Indexed keywords

AGENTS;

ANTIFUNGAL AGENTS;

SYNTHESIS (CHEMICAL);

ALCOHOL DERIVATIVE; CARBON; LACTONE; LEUCASCANDROLIDE A; MACROLIDE; OXAZOLE; TETRAHYDROPYRAN DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; CYTOTOXICITY; DIELS ALDER REACTION; DRUG ISOLATION; DRUG SYNTHESIS; LEUCASCANDRA CAVEOLATA; MITSUNOBU REACTION; REACTION ANALYSIS; SPONGE (PORIFERA); STEREOCHEMISTRY;

ANIMALS; PORIFERA; SESQUITERPENES; STEREOISOMERISM;

EID: 0037455379     PISSN: 14337851     EISSN: None     Source Type: Journal    
DOI: 10.1002/anie.200390112     Document Type: Article

References (31)

1. M. D'Ambrosio, A. Guerriero, C. Debitus, F. Pietra, Helv. Chim. Acta 1996, 79, 51.
2. M. D'Ambrosio, M. Tato, G. Pocsfalvi, C. Debitus, F. Pietra, Helv. Chim. Acta 1999, 82, 347.
3. K. R. Hornberger, C. L. Hamblett, J. L. Leighton, J. Am. Chem. Soc. 2000, 122, 12894.
4. For formal syntheses based on the endgame of Leighton, see: a) D. J. Kopecky, S. D. Rychnovsky, J. Am. Chem. Soc. 2001, 123, 8420; b) P. Wipf, J. T. Reeves, Chem. Commun. 2002, 2066. c) After submission of this manuscript, we were informed by Professor Carreira of his completed synthesis of leucascandrolide A, see: A. Fettes, E. M. Carreira, Angew. Chem. 2002, 114, 4272; Angew. Chem. Int. Ed. 2002, 41, 4098.
5. For formal syntheses based on the endgame of Leighton, see: a) D. J. Kopecky, S. D. Rychnovsky, J. Am. Chem. Soc. 2001, 123, 8420; b) P. Wipf, J. T. Reeves, Chem. Commun. 2002, 2066. c) After submission of this manuscript, we were informed by Professor Carreira of his completed synthesis of leucascandrolide A, see: A. Fettes, E. M. Carreira, Angew. Chem. 2002, 114, 4272; Angew. Chem. Int. Ed. 2002, 41, 4098.
6. For formal syntheses based on the endgame of Leighton, see: a) D. J. Kopecky, S. D. Rychnovsky, J. Am. Chem. Soc. 2001, 123, 8420; b) P. Wipf, J. T. Reeves, Chem. Commun. 2002, 2066. c) After submission of this manuscript, we were informed by Professor Carreira of his completed synthesis of leucascandrolide A, see: A. Fettes, E. M. Carreira, Angew. Chem. 2002, 114, 4272; Angew. Chem. Int. Ed. 2002, 41, 4098.
7. For formal syntheses based on the endgame of Leighton, see: a) D. J. Kopecky, S. D. Rychnovsky, J. Am. Chem. Soc. 2001, 123, 8420; b) P. Wipf, J. T. Reeves, Chem. Commun. 2002, 2066. c) After submission of this manuscript, we were informed by Professor Carreira of his completed synthesis of leucascandrolide A, see: A. Fettes, E. M. Carreira, Angew. Chem. 2002, 114, 4272; Angew. Chem. Int. Ed. 2002, 41, 4098.
8. For the synthesis of fragments of leucascandrolide, see: a) M. T. Crimmins, C. A. Carroll, B. W. King, Org. Lett. 2000, 2, 597; b) S. A. Kozmin, Org. Lett. 2001, 3, 755; c) P. Wipf, T. H. Graham, J. Org. Chem. 2001, 66, 3242.
9. For the synthesis of fragments of leucascandrolide, see: a) M. T. Crimmins, C. A. Carroll, B. W. King, Org. Lett. 2000, 2, 597; b) S. A. Kozmin, Org. Lett. 2001, 3, 755; c) P. Wipf, T. H. Graham, J. Org. Chem. 2001, 66, 3242.
10. For the synthesis of fragments of leucascandrolide, see: a) M. T. Crimmins, C. A. Carroll, B. W. King, Org. Lett. 2000, 2, 597; b) S. A. Kozmin, Org. Lett. 2001, 3, 755; c) P. Wipf, T. H. Graham, J. Org. Chem. 2001, 66, 3242.
11. I. Paterson, K. R. Gibson, R. M. Oballa, Tetrahedron Lett. 1996, 37, 8585.
12. D. A. Evans, P. J. Coleman, B. Coté, J. Org. Chem. 1997, 62, 788.
13. 2O (68%)
14. a) A. G. Dossetter, T. F. Jamison, E. N. Jacobsen, Angew. Chem. 1999, 111, 2549; Angew. Chem. Int. Ed. 1999, 38, 2398.
15. a) A. G. Dossetter, T. F. Jamison, E. N. Jacobsen, Angew. Chem. 1999, 111, 2549; Angew. Chem. Int. Ed. 1999, 38, 2398.
16. b) This reaction is believed to proceed through a highly ordered [4+2] cycloaddition in contrast to a Mukaiyama aldol/hetero-Michael pathway. For a review, see: K. A. Jorgensen, Angew. Chem. 2000, 112, 3702; Angew. Chem. Int. Ed. 2000, 39, 3559.
17. b) This reaction is believed to proceed through a highly ordered [4+2] cycloaddition in contrast to a Mukaiyama aldol/hetero-Michael pathway. For a review, see: K. A. Jorgensen, Angew. Chem. 2000, 112, 3702; Angew. Chem. Int. Ed. 2000, 39, 3559.
18. This homologation sequence was adapted from Evans and co- workers: D. A. Evans, D. M. Fitch, T. E. Smith, V. J. Cee. J. Am. Chem. Soc. 2000, 122, 10033.
19. 2 (73%)
20. The corresponding aldol addition with achiral aldehydes led to comparably high levels of 1,5-anti stereoinduction which indicates that chiral aldehyde 5 contributed only negligibly to 1,2- induction.
21. D. A. Evans, K. T. Chapman, E. M. Carreira, J. Am. Chem. Soc. 1988, 110, 3560.
22. A. De Mico, R. Margarita, L. Parlanti, A. Vescovi, G. Piancatelli, J. Org. Chem. 1997, 62, 6974.
23. V. H. Dahanukar, S. D. Rychnovsky, J. Org. Chem. 1996, 61, 8317.
24. 3, THF (79%) 6
25. I. Paterson, Tetrahedron Lett. 1979, 1519.
26. D. A. Evans, M. J. Dart, J. L. Duffy, M. G. Yang, J. Am. Chem. Soc. 1996, 118, 4322.
27. [4b] while this manuscript was in preparation.
28. C. W. Jefford, J.-C. Rossier, J. Boukouvalas, P. Huang, Helv. Chim. Acta 1994, 77, 661.
29. L. Banfi, G. Guanti, A. Basso, Eur. J. Org. Chem. 2000, 939.
30. N. F. Langille, L. A. Dakin, J. S. Panek, Org. Lett. 2002, 4, 2485.
31. 13C NMR spectra, see the Supporting Information.