Rapid synthesis of dendrimers by an orthogonal coupling strategy

Journal of the American Chemical Society

Volumn 118, Issue 22, 1996, Pages 5326-5327

  Zeng, Fanwen ^a   Zimmerman, Steven C ^a  

^a UNIVERSITY OF ILLINOIS AT URBANA CHAMPAIGN   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DENDRIMER; POLYMER;

ARTICLE; DRUG SYNTHESIS; ESTERIFICATION; GLYCOSYLATION; SPECTROSCOPY;

EID: 0030008363     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja960317s     Document Type: Article

References (36)

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2. For very recent reviews, see: Voit, B. I. Acta Polym. 1995, 46, 87-99. Ardoin, N.; Astruc, D. Bull. Soc, Chim. Fr. 1995, 132, 875-909. See also refs 6, 7, and 18a.
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4. Newkome, G. R.; Moorefield, C. N.; Baker, G. R.; Saunders, M. J.; Grossman, S. H. Angew. Chem. 1991, 103, 1207-1209. Hawker, C. J.; Wooley, K. L.; Fréchet, J. M. J. J. Chem. Soc., Perkin Trans. 1 1993, 1287-1297. Kim, Y. H.; Webster, O. W. J. Am. Chem. Soc. 1990, 112, 4592-4593. For metal-binding dendrimers, see: Nagasaki, T.; Kimura, O.; Ukon, M.; Arimori, S.; Hamachi, I.; Shinkai, S. J. Chem. Soc., Perkin Trans. I 1994, 75-81.
5. Newkome, G. R.; Moorefield, C. N.; Baker, G. R.; Saunders, M. J.; Grossman, S. H. Angew. Chem. 1991, 103, 1207-1209. Hawker, C. J.; Wooley, K. L.; Fréchet, J. M. J. J. Chem. Soc., Perkin Trans. 1 1993, 1287-1297. Kim, Y. H.; Webster, O. W. J. Am. Chem. Soc. 1990, 112, 4592-4593. For metal-binding dendrimers, see: Nagasaki, T.; Kimura, O.; Ukon, M.; Arimori, S.; Hamachi, I.; Shinkai, S. J. Chem. Soc., Perkin Trans. I 1994, 75-81.
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12. Tomalia, D. A.; Durst, H. D. Top. Curr. Chem. 1993, 165, 193-313. Tomalia, D. A. Aldrichimica Acta 1993, 26, 91-101. For early examples, see: Denkewalter, R. G.; Kole, J. F.; Lukasavage, W. J. U.S. Patent 4 410 688, 1979. Buhleier, E.; Wehner, W.; Vögtle, F. Synthesis 1978, 155-158.
13. Tomalia, D. A.; Durst, H. D. Top. Curr. Chem. 1993, 165, 193-313. Tomalia, D. A. Aldrichimica Acta 1993, 26, 91-101. For early examples, see: Denkewalter, R. G.; Kole, J. F.; Lukasavage, W. J. U.S. Patent 4 410 688, 1979. Buhleier, E.; Wehner, W.; Vögtle, F. Synthesis 1978, 155-158.
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24. To our knowledge, orthogonal dendrimer syntheses have been attempted only twice: (a) Twyman, L. J.; Beezer, A. E.; Milchell, J. C. J. Chem. Soc., Perkin Trans. I 1994, 407-411. (b) Spindler, R.; Fréchet, J. M. J. J. Chem. Soc., Perkin Trans, 1 1993, 913-918. Both syntheses were carried to the third-generation stage. In ref 14a orthogonality was not demonstrated, whereas in ref 14b it was achieved, but the third-generation dendrimer could not be separated from byproducts.
25. To our knowledge, orthogonal dendrimer syntheses have been attempted only twice: (a) Twyman, L. J.; Beezer, A. E.; Milchell, J. C. J. Chem. Soc., Perkin Trans. I 1994, 407-411. (b) Spindler, R.; Fréchet, J. M. J. J. Chem. Soc., Perkin Trans, 1 1993, 913-918. Both syntheses were carried to the third-generation stage. In ref 14a orthogonality was not demonstrated, whereas in ref 14b it was achieved, but the third-generation dendrimer could not be separated from byproducts.
26. (a) Monomer 1 was prepared by diazotization of commercially available 5-aminoisophthalic acid followed by treatment with sodium iodide (72% yield). Alcohol 2 was prepared from methyl 3,5-dibromobenzoate by reduction, coupling to (trimethylsilyl)acetylene, and deprotection with potassium carbonate (79% overall yield). (b) All compounds had spectral data in full accord with the assigned structures. Each compound except 14-16 was submitted for combustion analysis and gave passing results. The purity of 14-16 was estimated to be >97% from SEC and HPLC traces which each showed a single sharp peak. (c) Of course, the three steps do not include the several steps needed to make 8 and 9. The important point is that the orthogonal strategy minimizes the number of steps in the actual dendrimer synthesis, where purification is particularly difficult. The 13 to 14-16 conversion was carried out on a 200-600 mg scale; all other reactions were carried out on > 1 g scale.
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28. Mitsunobu, O. Synthesis 1981, 1-28. Hughes, D. L. Org. React. 1992, 42, 335-656.
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30. Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett. 1975, 4467-4470. Cassar, L. J. Organomet. Chem. 1975, 93, 253-257. Dieck, H. A.; Heck, R. F. J. Organomet. Chem. 1975, 93, 259-263.
31. Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett. 1975, 4467-4470. Cassar, L. J. Organomet. Chem. 1975, 93, 253-257. Dieck, H. A.; Heck, R. F. J. Organomet. Chem. 1975, 93, 259-263.
32. (a) Xu, Z.; Kyan, B.; Moore, J. S. In Advances in Dendritic Macromolecules; Newkome, G. R., Ed.; JAI: Greenwich,CT, 1994; Vol. 1, p 69.
33. (b) Zhang, J. S.; Pesak, D. J.; Ludwick, J. L.; Moore, J. S. J. Am. Chem. Soc. 1994, 116, 4227-4239.
34. This represents a general disadvantage of the convergent approach to dendrimer synthesis. However, the Mitsunobu and Sonogashira reactions are sterically demanding and were partly chosen as a stringent test of the orthogonal approach to dendrimer synthesis. Other coupling reactions are expected to proceed with higher yields and conversions.
35. Zimmerman, S. C.; Zeng, F.; Reichert, D. E. C.; Kolotuchin, S. V. Science 1996, 271, 1095-1098.
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