Total syntheses of dalesconol A and B

Angewandte Chemie - International Edition

Volumn 49, Issue 30, 2010, Pages 5146-5150

  Snyder, Scott A ^a   Sherwood, Trevor C ^a   Ross, Audrey G ^a  

^a Och Spine at New York Presbyterian Hospitals   (United States)

Author keywords

Cascade reaction; Natural products; Polycycles; Total synthesis

Indexed keywords

CASCADE REACTIONS; CHEMICAL EQUATIONS; NATURAL PRODUCTS; POLYCYCLES; POLYKETIDES; TOTAL SYNTHESIS;

REACTION INTERMEDIATES;

SYNTHESIS (CHEMICAL);

DALESCONOL A; DALESCONOL B; PHENOL; POLYCYCLIC AROMATIC HYDROCARBON;

ARTICLE; CHEMICAL STRUCTURE; CHEMISTRY; SYNTHESIS;

MOLECULAR STRUCTURE; PHENOL; POLYCYCLIC HYDROCARBONS, AROMATIC;

EID: 77954845322     PISSN: 14337851     EISSN: 15213773     Source Type: Journal    
DOI: 10.1002/anie.201002264     Document Type: Article

References (46)

1. Y. L. Zhang, H. M. Ge, W. Zhao, H. Dong, Q. Xu, S. H. Li, J. Li, J. Zhang, Y. C. Song, R. X. Tan, Angew. Chem. 2008, 120, 5907-5910;
2. Angew. Chem. Int. Ed. 2008, 47, 5823-5826.
3. For a recent total, synthesis of cyclosporin. A, see: X. Wu, J. L. Stockdill, P. Wang, S. J. Danishefsky, J. Am. Chem. Soc. 2010, 132, 4098-4100.
4. This unique biological activity can perhaps be explained if both enantiomers can enter the binding pocket, a phenomenon that was only just recently observed: M. Mentel, W Blankenfeldt, R. Breinbauer, Agew. Chem. 2009, 121, 9248-9251;
5. Agew. Chem. Int. Ed. 2009, 45, 9084-9087.
6. L. Wen, X. Cai, F. Xu, Z. She, W L. Chan, L. L. P. Vrijmoed, E. B. G. Jones, Y. Lin, J. Org. Chem. 2009, 74, 1093-1098.
7. a) S. A. Snyder, A. L. Zografos, Y. Lin, Angew. Chem. 2007, 119, 8334-8339;
8. Angew. Chem Int Ed. 2007, 46, 8186-8191;
9. b) S. A. Snyder, S. P. Breazzano, A. G. Ross, Y. Lin, A. L. Zografos, J. Am. Chem. Soc. 2009, 131, 1753-1765.
10. For the isolation and characterization of these three particular natural products, see:
11. a) K. Baba, K. Maeda, Y. Tabata, M. Doi, M. Kozawa, Chem Pharm. Bull 1988, 36, 2977-2983;
12. b) Y. Guo-Xun, Planta Med. 2005, 71, 569;
13. c) Y Oshima, Y Ueno, K. Hisamachi, M. Takeshita, Tetrahedron 1993, 49, 5801-5804.
14. For a related Stobbe condensation, see:
15. a) J. L. Bloomer, K. W. Stagliano, J. A. Gazzillo, J. Org. Chem. 1993, 58, 7906-7912. The preparation and use of phosphonate .13 was inspired by the following article:
16. b) M. Tamiya, K. Ohmori, M. Kitamura, H. Kato, T. Arai, M. Oorui, K. Suzuki, Chem. Eur. J. 2007, 13, 9791-9823.
17. a) M. Chae, J. Song, D. An, Bull. Korean Chem. Soc. 2007, 28, 2517-2518. The sodium and lithium analogs have been made as well:
18. b) J. I. Song, D. K. An, Chem. Lett. 2007, 36, 886-887;
19. c) M. S. Kim, Y. M. Choi, D. K. An, Tetrahedron Lett. 2007, 48, 5061-5064.
20. 4 to completely reduce the ester of 15, followed by Dess-Martin oxidation, afforded a commensurate yield of product, albeit at the cost of an additional synthetic step.
21. For recent uses of the alkali fusion reaction, see :
22. a) M. Poirier, M. Simard, J. D. Wuest, Organometallics 1996, 15, 1296-1300;
23. b) S. A. Snyder, Z.-Y. Tang, R. Gupta, J. Am. Chem. Soc. 2009, 131, 5744-5745.
24. With the double bond present, or with any oxidized form, of the double bond, the desired Friedel-Crafts cyclization could not be achieved. Therefore, a reduction, was required before a penultimate oxidation event to complete the targets. This change proved absolutely necessary in this case.
25. 2 to forge such types of systems is, of course, well known. For selected examples, see:
26. a) Y. Kita, T. Takada, M. Gyoten, H. Tohma, M. H. Zenk, J. Eichhorn, J. Org. Chem. 1996, 61, 5857-5864;
27. b) Y Kita, M. Arisawa, M. Gyoten, M. Nakajima, R. Hamada, H. Tohma, T. Takada, J. Org. Chem. 1998, 63, 6625-6633;
28. c) H. Tohma, H. Morioka, S. Takizawa, M. Arisawa, Y. Kita, Tetrahedron 2001, 57, 345-352;
29. d) I. R. Baxendale, S. V. Ley, C. Piutti, Angew. Chem 2002, 114, 2298-2301;
30. Angew. Chem. Int. Ed. 2002, 41, 2194-2197;
31. e) C. J. Lion, D. A. Vasselin, C. H. Schwalbe, C. S. Matthews, M. F. G. Stevens, A. D. Westwell, Org. Biomol. Chem. 2005, 3, 3996-4001;
32. f) I. R. Baxendale, J. Deeley, C. M. Griffiths-Jones, S. V. Ley, S. Saaby, G.K. Tranmer, Chem. Commun. 2006, 2566-2568;
33. g) D. R. Kelly, S. C. Baker, D. S. King, D. S. de Silva, G. Lord, J. P. Taylor, Org. Biomol. Chem 2008, 6, 787-796. However, to the best of our knowledge, the transformation has never been used in such a cascade event as described here. For excellent reviews on such reactions in synthesis, see:
34. h) L. Pouységu, D. Deffieux, S. Quideau, Tetrahedron 2010, 66, 2235-2261;
35. i) S. Quideau, L. Pouységu, D. Deffieux, Curr. Org. Chem. 2004, 8, 113-148.
36. Molecular modeling suggested that there would be a preference for the desired approach of hydrogen in this reaction, though the overall bias was not profound. For precedent that the desired hydrogenation could be achieved without loss of the benzylic ketone, see:
37. a) T. Kametani, H. Kondoh, M. Tsubuki, T. Honda, J. Chem. Soc Perkin Trans. 1 1990, 5-10;
38. b) D. H. Miles, D.-S. Lho, V. Chittawong, A. M. Payne, J. Org. Chem. 1990, 55, 4034-4036. Nevertheless, this reaction could be capricious, with overreduction easily achieved if the reaction was not carefully monitored, particularly on scale-up.
39. For a general reference on DDQ, see: D. R. Buckle in Encyclopedia of Reagents for Organic Synthesis, Vol. 3 (Ed.: L. A. Paquette), Wiley, Chichester, 1995, pp. 1299-1704.
40. a) J.-Q. Yu, E. J. Corey, Org. Lett. 2002, 4, 2727-2730;
41. b) J.-Q. Yu, E. J. Corey, J. Am. Chem. Soc 2003, 125, 3232-3233.
42. 2O, N-bromosuccinimide, and ceric ammonium nitrate (CAN).
43. The permethylated form, of 24 could also be oxidized into a ketone over two steps under the reported conditions; however, despite numerous attempts, it could never be fully deprotected to give dalesconol B (2) ; the nonhydrogen-bound phenol within ring A proved resistant to cleavage over several attempts.
44. -1' more stable than 26.
45. See the Supporting Information section for the synthetic route.
46. For a recent review on the concept of privileged architectures in drug discovery and development, see: M. Welsch, S. A. Snyder, B. S. Stockwell, Curr. Opin. Chem. Biology 2010, 14, 347-361.