General approach to epipolythiodiketopiperazine alkaloids: Total synthesis of (+)-chaetocins A and C and (+)-12,12′-dideoxychetracin A

Journal of the American Chemical Society

Volumn 132, Issue 41, 2010, Pages 14376-14378

  Kim, Justin ^a   Movassaghi, Mohammad ^a  

^a MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

GENERAL APPROACH; STEREO-SELECTIVE; TOTAL SYNTHESIS;

POLYSULFIDES;

12,12' DIDEOXYCHETRACIN A; ALKALOID; CHAETOCIN A; CHAETOCIN C; EPITETRATHIODIKETOPIPERAZINE DERIVATIVE; EPITRITHIODIKETOPIPERAZINE DERIVATIVE; PIPERAZINE DERIVATIVE; SULFIDE; UNCLASSIFIED DRUG;

ARTICLE; DIMERIZATION; DRUG SYNTHESIS; STEREOCHEMISTRY;

PIPERAZINES; STEREOISOMERISM;

EID: 77958057390     PISSN: 00027863     EISSN: 15205126     Source Type: Journal    
DOI: 10.1021/ja106869s     Document Type: Article

References (48)

1. Von Hauser, D., Weber, H. P., and Sigg, H. P. Helv. Chim. Acta 1970, 53, 1061
2. Saito, T., Suzuki, Y., Koyama, K., Natori, S., Iitaka, Y., and Knoshita, T. Chem. Pharm. Bull. 1988, 36, 1942
3. Greiner, D., Bonaldi, T., Eskeland, R., Roemer, E., and Imhof, A. Nat. Chem. Biol. 2005, 1, 143
4. Cherrier, T., Suzanne, S., Redel, L., Calao, M., Marban, C., Samah, B., Mukerjee, R., Schwartz, C., Gras, G., Sawaya, B. E., Zeichner, S. L., Aunis, D., Van Lint, C., and Rohr, O. Oncogene 2009, 28, 3380
5. Cook, K. M., Hilton, S. T., Mecinovic, J., Motherwell, W. B., Figg, W. D., and Schofield, C. J. J. Biol. Chem. 2009, 39, 26831
6. Isham, C. R., Tibodeau, J. D., Jin, W., Timm, M. M., and Bible, K. C. Blood 2010, 109, 2579
7. Lakshmikuttyamma, A., Scott, S. A., DeCoteau, J. F., and Geyer, C. R. Oncogene 2010, 29, 576
8. For the landmark synthesis of gliotoxin, see: Fukuyama, T., Nakatsuka, S., and Kishi, Y. Tetrahedron 1981, 37, 2045
9. For previous epidithiodiketopiperazine syntheses, see: Overman, L. E. and Sato, T. Org. Lett. 2007, 9, 5267 and references cited therein
10. Hino, T. and Sato, T. Tetrahedron Lett. 1971, 12, 3127
11. Ottenheijm, H. C. J., Herscheid, J. D. M., Kerkhoff, G. P. C., and Spande, T. F. J. Org. Chem. 1976, 41, 3433
12. Williams, R. M. and Rastetter, W. H. J. Org. Chem. 1980, 45, 2625
13. Wu, Z., Williams, L. J., and Danishefsky, S. J. Angew. Chem., Int. Ed. 2000, 39, 3866
14. Kim, J., Ashenhurst, J. A., and Movassaghi, M. Science 2009, 324, 238
15. Iwasa, E., Hamashima, Y., Fujishiro, S., Higuchi, E., Ito, A., Yoshida, M., and Sodeoka, M. J. Am. Chem. Soc. 2010, 132, 4078
16. For prior epitrithiodiketopiperazine syntheses, see: Brewer, D., Rahman, R., Safe, S., and Taylor, A. Chem. Commun. 1968, 1571
17. Murdock, K. C. and Angier, R. B. Chem. Commun. 1970, 55
18. Safe, S. and Taylor, A. J. Chem. Soc. C 1970, 3, 432
19. Reference 5b.
20. Ohler, E., Tatruch, F., and Schmidt, U. Chem. Ber. 1972, 105, 3658
21. Reference 5c.
22. Curtis, P. J., Greatbanks, D., Hesp, B., Cameron, A. F., and Freer, A. A. J. Chem. Soc. Perkin Trans. 1 1977, 180
23. Coffen, D. L., Katonak, D. A., Nelson, N. R., and Sancilio, F. D. J. Org. Chem. 1977, 42, 948
24. Kirby, G. W., Rao, G. V., Robins, D. J., and Stark, W. M. Tetrahedron Lett. 1986, 27, 5539 For prior epitetrathiodiketopiperazine syntheses, see: References 5b and 8b,8c,8g-8i.
25. Poisel, H. and Schmidt, U. Angew. Chem., Int. Ed. 1971, 10, 130
26. Yoshimura, J., Sugiyama, Y., Matsunari, K., and Nakamura, H. Bull. Chem. Soc. Jpn. 1974, 47, 1215
27. Strunz, G. M., Kakushima, M., and Stillwell, M. A. Can. J. Chem. 1975, 53, 295
28. Kirby, G. W., Robins, D. J., and Stark, M. J. Chem. Soc. Chem. Commun. 1983, 812
29. Waring, P., Eichner, R. D., Tiwari-Palni, U., and Mullbacher, A. Aust. J. Chem. 1987, 40, 991
30. Son, B. W., Jensen, P. R., Kauffman, C. A., and Fenical, W. Nat. Prod. Res. 1999, 13, 213
31. Movassaghi, M. Presented at the 239th National Meeting of the American Chemical Society, San Francisco, CA, March 2010; Paper ORGN 404.
32. Movassaghi, M., Schmidt, M. A., and Ashenhurst, J. A. Angew. Chem., Int. Ed. 2008, 47, 1485
33. Movassaghi, M. and Schmidt, M. A. Angew. Chem., Int. Ed. 2007, 46, 3725
34. See the Supporting Information for details.
35. Diastereocontrol was derived from dipole minimization effects in low-dielectric-constant media; the silyl ether function was imperative for the solubility of the notoriously insoluble diketopiperazines.
36. For the systematic positional numbering system used throughout this report, see p S3 in the Supporting Information.
37. For discussions of our first- and second-generation solutions to dimeric epidithiodiketopiperazines, see ref 6.
38. For challenges in purification of a diastereomeric mixture of intermediates in a route related to our first-generation solution to epidithiodiketopiperazine synthesis, see pp S7-S14 and S27-S28 in the Supporting Information for ref 7.
39. Exceptional control in the thiolation was achieved by stereoinduction from the proximal C3 stereocenter. Significant adverse C15 stereoinduction via anchimeric stabilization of the acyliminium ion by the acetate was minimized in high-dielectric-constant media.
40. An acetate proved to be too labile at C11 under the subsequent desulfonylation step, while attempts to use a pivaloate resulted in premature ionization.
41. Hamada, T., Nishida, A., and Yonemitsu, O. J. Am. Chem. Soc. 1986, 108, 140
42. The thioesters proved to be stable under the reductive photochemical conditions, in contrast to the corresponding thiols and polysulfides.
43. For epidithiodiketopiperazine synthesis using sulfenyl chlorides such as chloro(triphenylmethane)disulfane for thiol protection, see ref 5d. For preparation of this reagent, see
44. Williams, C. R., Britten, J. F., and Harpp, D. N. J. Org. Chem. 1994, 59, 806
45. 1H NMR shift reported for one of the diastereotopic protons at C12 of the major isomer is 3.60 ppm, but we found the resonance to be at 3.33 ppm.
46. It is heterodimeric with respect to the conformation of the two trisulfides.
47. The ratio was obtained at this temperature because trifluoroacetamide rotamer-derived peak broadening at lower temperatures prevented accurate integration of the peaks for the separate entities.
48. 1H NMR signal coalescence.