The total synthesis and biological properties of the cytotoxic macrolide FD-891 and its non-natural (Z)-C12 isomer

Chemistry - A European Journal

Volumn 13, Issue 18, 2007, Pages 5060-5074

  García Fortanet, Jorge ^a   Murga, Juan ^a   Carda, Miguel ^a   Marco, J Alberto ^b   Matesanz, Ruth ^c   Díaz, J Fernando ^c   Barasoain, Isabel ^c  

^a UNIVERSITAT JAUME I   (Spain)

^b UNIVERSITY OF VALENCIA   (Spain)

^c CENTRO DE INVESTIGACIONES BIOLÓGICAS   (Spain)

Author keywords

Aldol reaction; Allylation; Antitumor agents; Lactones; Olefination; Tubulin binding

Indexed keywords

ALDOL REACTION; ANTITUMOR AGENTS; MACROLACTONE RING; TUBULIN BINDING;

BINDING ENERGY; BIOSYNTHESIS; CYTOTOXICITY; ISOMERS; POLYMERIZATION;

TOXIC MATERIALS;

ALDEHYDE; ALKENE; ALLYL COMPOUND; ANTINEOPLASTIC AGENT; FD 891; MACROLIDE; TUBULIN; UNCLASSIFIED DRUG;

ARTICLE; BINDING SITE; CHEMISTRY; DRUG EFFECT; HUMAN; IC 50; ISOMERISM; METABOLISM; PATHOLOGY; SYNTHESIS; TUMOR CELL LINE; ULTRASTRUCTURE;

ALDEHYDES; ALKENES; ALLYL COMPOUNDS; ANTINEOPLASTIC AGENTS; BINDING SITES; CELL LINE, TUMOR; HUMANS; INHIBITORY CONCENTRATION 50; ISOMERISM; MACROLIDES; TUBULIN;

EID: 34250893238     PISSN: 09476539     EISSN: 15213765     Source Type: Journal    
DOI: 10.1002/chem.200700342     Document Type: Article

References (80)

1. a) S. Dröse, K. Altendorf, J. Exp. Biol. 1997, 200, 1-8;
2. b) Further additional mechanisms of action cannot be excluded: J. J. Shacka, B. J. Klocke, K. A. Roth, Autophagy 2006, 2, 228-230.
3. a) K. Toshima, Curr. Org. Chem. 2004, 8, 185-210;
4. b) W.-M. Dai, Y. Guan, J. Jin, Curr. Med. Chem. 2005, 12, 1947-1993.
5. a) K. U. Bindseil, A. Zeeck, J. Org. Chem. 1993, 58, 5487-5492;
6. b) K.U. Bindseil, A. Zeeck, Liebigs Ann. Chem. 1994, 305-312;
7. c) G. Ingenhorst, K. U. Bindseil, C. Boddien, S. Dröse, M. Gassel, K. Altendorf, A. Zeeck, Eur. J. Org. Chem. 2001, 4525-4532.
8. a) S. Gagliardi, F. A. Gatti, P. Belfiore, A. Zocchetti, G. D. Clarke, C. Farina, J. Med. Chem. 1998, 41, 1883-1893;
9. b) K. D. Hettiarachchi, P. Z. Zimmet, M. A. Myers, Cell Biol. Toxicol. 2006, 22, 169-181;
10. c) K. D. Hettiarachchi, P. Z. Zimmet, M. A. Myers, Food Chem. Toxicol. 2006, 44, 1966-1977.
11. M. Seki-Asano, Y. Tsuchida, K. Hanada, K. Mizoue, J. Antibiot. 1994, 47, 1234-1241.
12. T. Kataoka, A. Yamada, M. Bando, T. Honma, K. Mizoue, K. Nagai, Immunology 2000, 100, 170-177 (Erratum: Immunology 2000, 101, 288).
13. M. Natsume, M. Komiya, F. Koyanagi, N. Tashiro, H. Kawaide, H. Abe, J. Gen. Plant Pathol. 2005, 71, 364-369.
14. a) T. Eguchi, K. Kobayashi, H. Uekusa, Y. Ohashi, K. Mizoue, Y. Matsushima, K. Kakinuma, Org. Lett. 2002, 4, 3383-3386;
15. b) T. Eguchi, K. Yamamoto, K. Mizoue, K. Kakinuma, J. Antibiot. 2004, 57, 156-157.
16. a) M. Bartra, F. Urpí, J. Vilarrasa in Recent Progress in the Chemical Synthesis of Antibiotics and Related Microbial Products (Ed.: G. Lukacs), Springer Verlag, Berlin, Vol. 2, 1993, pp. 1-65;
17. b) A. Parenty, X. Moreau, J.-M. Campagne, Chem. Rev. 2006, 106, 911-939.
18. I. Ojima, M. Tzamarioudaki, Z.-Y. Li, R. J. Donovan, Chem. Rev. 1996, 96, 635-662.
19. For a preliminary communication see: J. Murga, J. García-Fortanet, M. Carda, J. A. Marco, Tetrahedron Lett. 2004, 45, 7499-7501.
20. a) H. C. Brown, P. V. Ramachandran, J. Organomet. Chem. 1995, 500, 1-19;
21. b) P. V. Ramachandran, Aldrichimica Acta 2002, 35, 23-35.
22. a) D. A. Evans, Aldrichimica Acta 1982, 15, 23-32;
23. b) B.M. Kim, S. F. Williams, S. Masamune in Comprehensive Organic Synthesis, Vol.2 (Eds.: B. M. Trost, I. Fleming, E. Winterfeldt), Pergamon Press, Oxford, 1993, pp. 239-276;
24. c) C. J. Cowden, I. Paterson, Org. React. 1997, 57, 1-200.
25. K. C. Nicolaou, K. Namoto, A. Ritzén, T. Ulven, M. Shoji, J. Li, G. D'Amico, D. Liotta, C. T. French, M. Wartmann, K. H. Altmann, P. Giannakakou, J. Am. Chem. Soc. 2001, 123, 9313-9323.
26. However, we have prepared 10 via an adaptation of one route described for the TBS analogue: S. Chandrasekhar, C. R. Reddy, Tetrahedron: Asymmetry 2002, 13, 261 -268.
27. M. P. Sibi, Org. Prep. Proced. Int. 1993, 25, 15-40.
28. 3). Therefore, we resorted to the alternative method described in Scheme 3.
29. D. A. Evans, B. D. Allison, M. G. Yang, C. E. Masse, J. Am. Chem. Soc. 2001, 123, 10840-10852.
30. See also: T. Ooi, J. Morikawa, D. Uraguchi, K. Maruoka, Tetrahedron Lett. 1999, 40, 2993-2996.
31. 2AlCl, we tested reductants such as DIBAL and L-selectride, which have proven useful in closely related instances (D. L. Boger, T. T. Curran, J. Org. Chem. 1992, 57, 2235-2244). However, they displayed a low stereoselectivity in the present case (dr = about 2:1).
32. 13C NMR spec troscopic signals at approximately 30 and 19ppm. This indicates that it is the acetonide of a syn-1,3-diol [20] and can only be that indicated below, as the internal acetonide would necessarily be anti.
33. S. D. Rychnovsky, B. N. Rogers, T. I. Richardson, Acc. Chem. Res. 1998, 31, 9-17.
34. D.M. Walba, W. N. Thurmes, R. C. Haltiwanger, J. Org. Chem. 1988, 53, 1046-1056. Meerwein's salt (trimethyloxonium tetrafluoroborate) proved ineffective in the present case.
35. S. Hatakeyama, H. Irie, T. Shintani, Y. Noguchi, H. Yamada, M. Nishizawa, Tetrahedron 1994, 50, 13369-13376.
36. T. W. Greene, P. G. M. Wuts, Protective Groups in Organic Synthesis; John Wiley and Sons, New York, 3rd ed., 1999, pp. 27-33.
37. P. R. Blakemore, J. Chem. Soc. Perkin Trans. 1 2002, 2563-2585.
38. For the synthesis of a compound structurally related to fragment 23 see: S.-S. Chng, J. Xu, T.-P. Loh, Tetrahedron Lett. 2003, 44, 4997-5000.
39. For a preliminary communication see: J. Murga, J. García-Fortanet, M. Carda, J. A. Marco, Synlett 2004, 2830-2832. Several improvements and optimisations with respect to the published synthesis are reported now.
40. B. M. Trost, J. D. Chisholm, S. T. Wrobleski, M. Jung, J. Am. Chem. Soc. 2002, 124, 12420-12421.
41. This Z→E isomerisation during the oxidation with PCC has been reported to occur with the corresponding benzyl derivative: S. J. Danishefsky, E. M. Berman, M. Ciufolini, S. J. Etheredge, B. E. Segmuller, J. Am. Chem. Soc. 1985, 107, 3891-3898.
42. This olefination gave a better yield in 1,2-dichloroethane at 60°C than in toluene at 110°C, in contrast to that observed in a structurally similar situation: J. A. Marshall, N. D. Adams, J. Org. Chem. 2002, 67, 733-740.
43. a) W. Oppolzer, Tetrahedron 1987, 43, 1969-2004;
44. b) W. Oppolzer, J. Blagg, I. Rodriguez, E. Walther, J. Am. Chem. Soc. 1990, 112, 2767-2772;
45. c) O. Reiser, Nachr. Chem. Tech. Lab. 1996, 44, 612-618.
46. This change of the chiral auxiliary was motivated by the saving of one step, as we were able to directly reduce the silylated aldol adducts to aldehydes, thus circumventing the preparation of Weinreb amides. Furthermore, the first reduction-olefination sequence worked much better with the Oppolzer auxiliary (38→35, 88% overall yield) than via the Weinreb amide (34-35, 55% overall yield).
47. K. Horita, T. Yoshioka, T. Tanaka, Y. Oikawa, O. Yonemitsu, Tetrahedron 1986, 42, 3021-3028.
48. T. Katsuki, V. S. Martín, Org. React. 1996, 48, 1-300.
49. a) M. B. Andrus, S. D. Lepore, F. A. Sclafani, Tetrahedron Lett. 1997, 38, 4043-4046;
50. b) M. B. Andrus, T. M. Turner, D. Asgari, W. Li, J. Org. Chem. 1999, 64, 2978-2979.
51. Y.-L. Zhong, T. K. M. Shing, J. Org, Chem. 1997, 62, 2622-2624.
52. a) Preliminary report on the total synthesis of FD-891 : J. García-Fortanct, J. Murga, M. Carda, J. A. Marco, Org. Lett. 2006, 8, 2695-2698;
53. h) for another recently published synthesis of FD-891 see: M. T. Crimmins, F. Caussanel, J. Am. Chem. Soc. 2006, 128, 3128-3129.
54. M. A. Blanchette, M.S. Malamas, M. H. Nantz, J. C. Roberts, P. Somfai, D. C. Whritenour, S. Masamune. J. Org. Chem. 1989, 54. 2817-2825.
55. A. P. Kozikowski, P. D. Stein, J. Org. Chem. 1984, 49, 2301-2309.
56. The absolute configuration of aldol 51 has been secured by means of X-ray diffraction analysis (see the Supporting Information in reference [36a]).
57. Silylation of 51 required the use of a considerable excess of silylating agent. Therefore, purification of 52 proved difficult. For this reason, overall yield is given for the three steps 51→54.
58. P. R. Blakemore, P. J. Kocienski, A. Morley, K. Muir, J. Chem. Soc. Perkin Trans. 1 1999, 955-968.
59. S. V. Voitekhovich, P. N. Gaponik, G. I. Koldobskii, Russ. J. Org. Chem. 2005, 41, 1565-1582.
60. a) O. Mitsunobu, Synthesis 1981, 1-28;
61. b) D. L. Hughes, Org. React. 1992, 42, 335-656;
62. c) D. H. Valentine Jr, J. H. Hillhouse, Synthesis 2003, 317-334.
63. T. Masuda, K. Osako, T. Shimizu, T. Nakata, Org. Lett. 1999, 1, 941-944.
64. Under the standard conditions for the Julia-Kocienski reaction (KHMDS, THF), we obtained an 80:20 E/Z mixture but in only 23% yield, even when using a fourfold excess of aldehyde 23. No improvement in yield or stereoselectivity could be achieved.
65. a) Y. Guindon, H. E. Morton, C. Yoakim, Tetrahedron Lett. 1983, 24, 3969-3972;
66. b) Y. Guindon, C. Yoakim, H. E. Morton, J. Org. Chem. 1984, 49, 3912-3920.
67. The assignments of configuration to the newly formed olefinic bond in each isomer was difficult because of strong signal overlapping. The problem could be finally solved by NMR spectroscopic measurements at very high field (800 MHz, see acknowledgments).
68. E. D. Laganis, B. L. Chenard, Tetrahedron Lett. 1984, 25, 5831-5834.
69. J. Inanaga, K. Hirata, H. Saeki, T. Katsuki, M. Yamaguchi, Bull. Chem. Soc. Jpn. 1979, 52, 1989-1993.
70. K. A. Scheidt, H. Chen, B. C. Follows, S. R. Chemler, D. S. Coffey, W. R. Roush, J. Org. Chem. 1998, 63, 6436-6437.
71. The identity of the final desilylation product 2 was confirmed through comparison with an authentic sample of the natural product (see the Acknowledgements).
72. Cleavage of the silyl groups at C-7 and C-10 takes place with ease. In contrast, those allocated at C-21 and C-23 proved unexpectedly reluctant to cleavage under various mild conditions (too harsh conditions caused decomposition). These two groups are thus responsible for the unsatisfactory yield in the final desilylation step. Such problematic deprotections are not unprecedented: T. B. Durham, N. Blanchard, B. M. Savall, N. A. Powell, W. R. Roush, J. Am. Chem. Soc. 2004, 126, 9307-9317.
73. R. J. Kowalski, P. Giannakakou, S. P. Gunasekera, R. E. Longley, B. W. Day, E. Hamel, Mol. Pharmacol. 1997, 52, 613-622.
74. A. I. Marcus, A. M. O'Brate, R. M. Buey, J. Zhou, S. Thomas, F. R. Khuri, J. M. Andreu, F. Díaz, and P. Giannakakou, Cancer Res. 2006, 66, 8838-8846.
75. C. de Ines, D. Leynadier, I. Barasoain, V. Peyrot, P. Garcia, C. Briand, G. A. Rener, C. Temple, Jr., Cancer Res. 1994, 54, 75-84.
76. R. M. Buey, I. Barasoain, E. Jackson, A. Meyer, P. Giannakakou, I. Paterson, S. Mooberry, J. M. Andreu, J. F. Díaz, Chem. Biol. 2005, 12, 1269-1279.
77. J. M. Andreu, I. Barasoain, Biochemistry 2001, 40, 11975-11984.
78. J. F. Díaz, J. M. Andreu, Biochemistry 1993, 32, 2747-2755.
79. M. M. Bradford, Anal. Biochem. 1976, 72, 248-254.
80. R. M. Buey, J. F. Díaz, J. M. Andreu, A. O'Brate, P. Giannakakou, K. C. Nicolaou, P. K. Sasmal, A. Ritzén, K. Namoto, Chem. Biol. 2004, 11, 225-236.