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3. (a) Bondeson, D. P.; Mares, A.; Smith, I. E. D.; Ko, E.; Campos,
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Besten, W.; Famm, K.; Kruidenier, L.; Carter, P. S.; Harling, J.
D.; Churcher, I.; Crews, C. M. Nat. Chem. Biol. 2015, 11, 611; (b)
Lu, J.; Qian, Y.; Altieri, M.; Dong, H.; Wang, J.; Raina, K.; Hines,
J.; Winkler, J. D.; Crew, A. P.; Coleman, K.; Crews, C. M. Chem.
Biol. 2015, 22, 755; (c) Zengerle, M.; Chan, K.-H.; Ciulli, A. ACS
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E. Science 2015, 348, 1376. (e) Lai, A. C.; Toure, M.;
Hellerschmied, D.; Salami, J.; Jaime-Figueroa, S.; Ko, E.; Hines,
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4. Schneekloth, A. R.; Pucheault, H. S.; Tae, H. S.; Crews, C. M.
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6. (a) Buckley, D. L.; Gustafson, J. L.; Van Molle, I.; Roth, A. G.;
Tae, S. S.; Gareiss, P. C.; Jorgensen, W. L.; Ciulli, A.; Crews, C.
M. Angew. Chem. Int. Ed. 2012, 51, 11463; (b) Galdeano, C.;
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7. In reference 3e, Crews et al. have shown that pomalidomide can
be acylated to give PROTAC precursors.
Scheme 2: Synthesis of four PROTAC precursors. (a) H2N-linker-NHBoc
(1.1 equiv.), HATU (1.1 equiv.), i-Pr2NEt (2.0 equiv.), CH2Cl2, 85% for 10,
34% for 11, 80% for 12, 82% for 13; (b) TFA/CH2Cl2 (1:5), quantitative for
10–13.
Acknowledgments
8. Eliel, E. L.; Burgstahler, A. W.; Rivard, D. E.; Haefele, L. J. Am.
Chem. Soc. 1955, 77, 5092.
We gratefully acknowledge the Helmholtz Drug Research
Initiative (Helmholtz Wirkstoffforschung) for funding and the
NMR Structure Analysis Facility of the DKFZ and the Mass
Spectrometry Facility at the Organic Chemistry Institute of the
University of Heidelberg for analytical services.
9. (a) Capitosti, S. M.; Hansen T. P.; Brown, M. L. Org. Lett. 2003,
5, 2865; (b) Stewart, S. G.; Braun, C. J.; Ng, S.-L.; Polomska, M.
E.; Karimi, M.; Abraham, L. J. Bioorg. Med. Chem. 2010, 18, 650.
10. Luo, W; Yu, Q.-S.; Tweedie, D.; Deschamps, J.; Parrish, D.;
Holloway, H. W.; Li, Y.; Brossi, A.; Greig, N. H. Synthesis 2008,
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References and notes
11. Ruchelman, A. L.; Muller, G. W.; Man, H.-W. PCT Int. App.
WO2008/115516 A2, 2008.
1. For reviews see: (a) Toure, M.; Crews, C. M. Angew. Chem. Int.
Ed. 2016, 55, 1966; (b) Buckley, D. L.; Crews, C. M. Angew.
Chem. Int. Ed. 2014, 53, 2312.
Supplementary Material
2. (a) Long, M. J. C.; Gollapalli, D. R.; Hedstrom, L. Chem. Biol.
2012, 19, 629; (b) Xie, T.; Lim, S. M.; Westover, K. D.; Dodge,
M. E.; Ercan, D.; Ficarro, S. B.; Udayakumar, D.; Gurbani, D.;
Experimental procedures and analytical data can be found in
the online version.