Synthetic carbohydrate-containing dendrimers

Chemistry - A European Journal

Volumn 3, Issue 8, 1997, Pages 1193-1199

  Jayaraman, Narayanaswamy ^a   Nepogodiev, Sergey A ^a   Stoddart, J Fraser ^a  

^a UNIVERSITY OF BIRMINGHAM   (United Kingdom)

Author keywords

Carbohydrates; Cluster glycosides; Convergent synthesis; Dendfimers; Divergent synthesis

Indexed keywords

EID: 0030767347     PISSN: 09476539     EISSN: None     Source Type: Journal    
DOI: 10.1002/chem.19970030804     Document Type: Review

References (65)

1. For authoritative and comprehensive reviews on dendrimers, see: a) D. A. Tomalia, A. M. Naylor, W. A. Goddard III, Angew. Chem. Int. Ed. Engl. 1990, 29, 138-175; b) J. Issberner, R. Moors, F. Vögtle, Angew. Chem. Int. Ed. Engl. 1994, 33, 2413-2420; c) J. M. J. Fréchet, Science, 1994, 263, 1710-1715; d) G. R. Newkome, C. N. Moorefield, F. Vögtle, Dendritic Molecules: Concepts, Syntheses, Perspectives, VCH, Weinheim, 1996.
2. For authoritative and comprehensive reviews on dendrimers, see: a) D. A. Tomalia, A. M. Naylor, W. A. Goddard III, Angew. Chem. Int. Ed. Engl. 1990, 29, 138-175; b) J. Issberner, R. Moors, F. Vögtle, Angew. Chem. Int. Ed. Engl. 1994, 33, 2413-2420; c) J. M. J. Fréchet, Science, 1994, 263, 1710-1715; d) G. R. Newkome, C. N. Moorefield, F. Vögtle, Dendritic Molecules: Concepts, Syntheses, Perspectives, VCH, Weinheim, 1996.
3. For authoritative and comprehensive reviews on dendrimers, see: a) D. A. Tomalia, A. M. Naylor, W. A. Goddard III, Angew. Chem. Int. Ed. Engl. 1990, 29, 138-175; b) J. Issberner, R. Moors, F. Vögtle, Angew. Chem. Int. Ed. Engl. 1994, 33, 2413-2420; c) J. M. J. Fréchet, Science, 1994, 263, 1710-1715; d) G. R. Newkome, C. N. Moorefield, F. Vögtle, Dendritic Molecules: Concepts, Syntheses, Perspectives, VCH, Weinheim, 1996.
4. For authoritative and comprehensive reviews on dendrimers, see: a) D. A. Tomalia, A. M. Naylor, W. A. Goddard III, Angew. Chem. Int. Ed. Engl. 1990, 29, 138-175; b) J. Issberner, R. Moors, F. Vögtle, Angew. Chem. Int. Ed. Engl. 1994, 33, 2413-2420; c) J. M. J. Fréchet, Science, 1994, 263, 1710-1715; d) G. R. Newkome, C. N. Moorefield, F. Vögtle, Dendritic Molecules: Concepts, Syntheses, Perspectives, VCH, Weinheim, 1996.
5. A. Varki, Glycobiology 1993, 3, 97-130.
6. The rapidly growing interest in carbohydrate-protein interactions has led to the evolution of glycobiology as a field of intense scientific inquiry. For an excellent review, see: R. Dwek, Chem. Rev. 1996, 96, 683-720.
7. a) K. Toshima, K. Tatsuta, Chem. Rev. 1993, 93, 1503-1531;
8. b) G.-J. Boons, Tetrahedron, 1996, 52, 1095-1121,
9. c) S. J. Danishefsky, M. T. Bilodeau, Angew. Chem. Int. Ed. Engl. 1996, 35, 1380-1419.
10. The majority of the research performed in this area is directed toward creating synthetic analogues of natural glycoconjugates - the so-called neoglycoconjusates. These compounds provide an insight into the biological functions of saccharides and are an indispensable aid to understanding many aspects of glycobiology. For leading references, see: a) C. P. Stowell, Y. C. Lee, Adv. Carbohydr. Chem. Biochem. 1980, 37, 225-281; b) Neoglycoconjugates: Preparation and Applications (Eds.: Y. C. Lee, R. T. Lee). Academic Press, San Diego, 1994; c) Methods in Enzymology, Vol. 242, Neoglycoconjugates, Part A, Synthesis (Eds.: Y. C. Lee and R. T. Lee), Academic Press, San Diego, 1994; d) Methods in Enzymology, Vol. 247, Neoglycoconjugates, Part B, Biomedical Applications (Eds.: Y. C. Lee and R. T. Lee), Academic Press, San Diego, 1994.
11. The majority of the research performed in this area is directed toward creating synthetic analogues of natural glycoconjugates - the so-called neoglycoconjusates. These compounds provide an insight into the biological functions of saccharides and are an indispensable aid to understanding many aspects of glycobiology. For leading references, see: a) C. P. Stowell, Y. C. Lee, Adv. Carbohydr. Chem. Biochem. 1980, 37, 225-281; b) Neoglycoconjugates: Preparation and Applications (Eds.: Y. C. Lee, R. T. Lee). Academic Press, San Diego, 1994; c) Methods in Enzymology, Vol. 242, Neoglycoconjugates, Part A, Synthesis (Eds.: Y. C. Lee and R. T. Lee), Academic Press, San Diego, 1994; d) Methods in Enzymology, Vol. 247, Neoglycoconjugates, Part B, Biomedical Applications (Eds.: Y. C. Lee and R. T. Lee), Academic Press, San Diego, 1994.
12. The majority of the research performed in this area is directed toward creating synthetic analogues of natural glycoconjugates - the so-called neoglycoconjusates. These compounds provide an insight into the biological functions of saccharides and are an indispensable aid to understanding many aspects of glycobiology. For leading references, see: a) C. P. Stowell, Y. C. Lee, Adv. Carbohydr. Chem. Biochem. 1980, 37, 225-281; b) Neoglycoconjugates: Preparation and Applications (Eds.: Y. C. Lee, R. T. Lee). Academic Press, San Diego, 1994; c) Methods in Enzymology, Vol. 242, Neoglycoconjugates, Part A, Synthesis (Eds.: Y. C. Lee and R. T. Lee), Academic Press, San Diego, 1994; d) Methods in Enzymology, Vol. 247, Neoglycoconjugates, Part B, Biomedical Applications (Eds.: Y. C. Lee and R. T. Lee), Academic Press, San Diego, 1994.
13. The majority of the research performed in this area is directed toward creating synthetic analogues of natural glycoconjugates - the so-called neoglycoconjusates. These compounds provide an insight into the biological functions of saccharides and are an indispensable aid to understanding many aspects of glycobiology. For leading references, see: a) C. P. Stowell, Y. C. Lee, Adv. Carbohydr. Chem. Biochem. 1980, 37, 225-281; b) Neoglycoconjugates: Preparation and Applications (Eds.: Y. C. Lee, R. T. Lee). Academic Press, San Diego, 1994; c) Methods in Enzymology, Vol. 242, Neoglycoconjugates, Part A, Synthesis (Eds.: Y. C. Lee and R. T. Lee), Academic Press, San Diego, 1994; d) Methods in Enzymology, Vol. 247, Neoglycoconjugates, Part B, Biomedical Applications (Eds.: Y. C. Lee and R. T. Lee), Academic Press, San Diego, 1994.
14. The term glycodendrimers has also been suggested by Roy for this class of compounds: in practice, it is used for dendrimers, dendrons, and even compounds consisting of relatively small multi-antennary molecules. An article entitled Glycodendrimere has recently been published in German; see: TK Lindhorst, Nachr. Chem. Tech. Lab. 1996, 44, 1073-1079.
15. For a discussion on the wide range of building blocks available for constructing dendrimers, see: G. R. Newkome, C. N. Moorefield, G. R. Baker, Aldrichim. Acta. 1992, 25, 31-38.
16. P. R. Ashton, S. E. Boyd, C. L. Brown, N. Jayaraman, S. A. Nepogodiev, J. F. Stoddart, Chem. Eur. J. 1996, 2, 1115-1128.
17. P. R. Ashton, S. E. Boyd, C. L. Brown, N. Jayaraman, J. F. Stoddart, Angew. Chem. Int. Ed. Engl. 1997, 36, 732-735.
18. Glycopeptides are usually assembled from glycosylated amino acids, rather than by the glycosylation of pre-formed peptides. See: a) M. Meldal, in Neoglycoconjugates: Preparation and Applications (Eds.: Y. C. Lee and R. T. Lee), Academic Press, San Diego, 1994, pp. 145-198; b) H. Paulsen, S. Peters, T. Bielfieldt in New Comprehensive Biochemistry, Vol. 29, Glycoproteins (Eds.: J. Montreuil, J. F. G. Vliegenthart, H. Schachter), Elsevier, Amsterdam, 1995, pp. 87-121.
19. Glycopeptides are usually assembled from glycosylated amino acids, rather than by the glycosylation of pre-formed peptides. See: a) M. Meldal, in Neoglycoconjugates: Preparation and Applications (Eds.: Y. C. Lee and R. T. Lee), Academic Press, San Diego, 1994, pp. 145-198; b) H. Paulsen, S. Peters, T. Bielfieldt in New Comprehensive Biochemistry, Vol. 29, Glycoproteins (Eds.: J. Montreuil, J. F. G. Vliegenthart, H. Schachter), Elsevier, Amsterdam, 1995, pp. 87-121.
20. K. Aoi, K. Itoh, M. Okada, Macromolecules 1995, 28, 5391-5393.
21. D. A. Tomalia, H. Baker, J. Dewald, M. Hall, G. Kallos, S. Martin, J. Roeck, J. Ryder, P. Smith, Polym. J. 1985, 17, 117-132. A range of Tomalia's PAMAM dendrimers from generations one to five is now available from the Aldrich Chemical Company.
22. Most of the synthetic techniques rely upon covalent bond formation between spacer-armed saccharides and functional groups on the polymer carriers. For more details, consult ref. [5].
23. K. Lindhorst, C. Kieburg, Angew. Chem. Int. Ed. Engl. 1996, 35, 1953-1956.
24. D. Pagé, S. Aravind, R. Roy, Chem. Commun. 1996, 1913-1914.
25. P. R. Ashton, S. E. Boyd, C. L. Brown, S. A. Nepogodiev, E. W. Meijer, H. W. I. Peerlings, J. F. Stoddart, Chem. Eur. J. 1997, 3, 974-984.
26. a) E. M. M. de Brabander-van den Berg, E. W. Meijer, Angew. Chem. Int. Ed. Engl. 1993, 32, 1308-1311;
27. b) E. M. M. de Brabander-van den Berg, A. Nijenhuis, M. Muré, J. Keulen, R. Reintjens, F. Vandenbooren, B. Bosman, R. de Raat, T Frijns, S. van der Wal, M. Castelijns, J. Put, E. W. Meijer, Macromol. Symp. 1994, 77, 51-62.
28. R. T. Lee, Y. C. Lee in Neoglycoconjugates: Preparation and Applications (Eds.: Y. C. Lee. R. T. Lee), Academic Press, San Diego, 1994, pp. 23-50.
29. For a selection of some recent papers, see: a) U. Sprengard, M. Schudok, W. Schmidt, G. Kretzschmer, H. Kunz, Angew. Chem. Int. Ed. Engl. 1996, 35, 321-324; b) S. A. DeFrees, W. Kosch, W. Way, J. C. Paulson, S. Sabesan, R. L. Halcomb, D.-H. Huang, Y. Ichikawa, C.-H. Wong, J. Am. Chem. Soc. 1995, 117, 66-79; c) E. R. Wijsman, D. Filippov, A. R. P. M. Valentijn, G. A. van der Marel, J. H. van Boom, Rec. Trav. Chim. Pays-Bas 1996, 115, 397-401; d) A. Kichler, F. Schuber, Glycoconj. J. 1995, 12, 275-281; e) J. Lehman, U. P. Weitzel, Carbohydr. Res. 1996, 294, 65-94; f) A. R. P. M. Valentijn, G. A. van der Marel, L. A. J. M. Sliedregt, T. J. C. van Berkel, E. A. L. Biessen, J. H. van Boom, Tetrahedron 1997, 53, 759-770.
30. For a selection of some recent papers, see: a) U. Sprengard, M. Schudok, W. Schmidt, G. Kretzschmer, H. Kunz, Angew. Chem. Int. Ed. Engl. 1996, 35, 321-324; b) S. A. DeFrees, W. Kosch, W. Way, J. C. Paulson, S. Sabesan, R. L. Halcomb, D.-H. Huang, Y. Ichikawa, C.-H. Wong, J. Am. Chem. Soc. 1995, 117, 66-79; c) E. R. Wijsman, D. Filippov, A. R. P. M. Valentijn, G. A. van der Marel, J. H. van Boom, Rec. Trav. Chim. Pays-Bas 1996, 115, 397-401; d) A. Kichler, F. Schuber, Glycoconj. J. 1995, 12, 275-281; e) J. Lehman, U. P. Weitzel, Carbohydr. Res. 1996, 294, 65-94; f) A. R. P. M. Valentijn, G. A. van der Marel, L. A. J. M. Sliedregt, T. J. C. van Berkel, E. A. L. Biessen, J. H. van Boom, Tetrahedron 1997, 53, 759-770.
31. For a selection of some recent papers, see: a) U. Sprengard, M. Schudok, W. Schmidt, G. Kretzschmer, H. Kunz, Angew. Chem. Int. Ed. Engl. 1996, 35, 321-324; b) S. A. DeFrees, W. Kosch, W. Way, J. C. Paulson, S. Sabesan, R. L. Halcomb, D.-H. Huang, Y. Ichikawa, C.-H. Wong, J. Am. Chem. Soc. 1995, 117, 66-79; c) E. R. Wijsman, D. Filippov, A. R. P. M. Valentijn, G. A. van der Marel, J. H. van Boom, Rec. Trav. Chim. Pays-Bas 1996, 115, 397-401; d) A. Kichler, F. Schuber, Glycoconj. J. 1995, 12, 275-281; e) J. Lehman, U. P. Weitzel, Carbohydr. Res. 1996, 294, 65-94; f) A. R. P. M. Valentijn, G. A. van der Marel, L. A. J. M. Sliedregt, T. J. C. van Berkel, E. A. L. Biessen, J. H. van Boom, Tetrahedron 1997, 53, 759-770.
32. For a selection of some recent papers, see: a) U. Sprengard, M. Schudok, W. Schmidt, G. Kretzschmer, H. Kunz, Angew. Chem. Int. Ed. Engl. 1996, 35, 321-324; b) S. A. DeFrees, W. Kosch, W. Way, J. C. Paulson, S. Sabesan, R. L. Halcomb, D.-H. Huang, Y. Ichikawa, C.-H. Wong, J. Am. Chem. Soc. 1995, 117, 66-79; c) E. R. Wijsman, D. Filippov, A. R. P. M. Valentijn, G. A. van der Marel, J. H. van Boom, Rec. Trav. Chim. Pays-Bas 1996, 115, 397-401; d) A. Kichler, F. Schuber, Glycoconj. J. 1995, 12, 275-281; e) J. Lehman, U. P. Weitzel, Carbohydr. Res. 1996, 294, 65-94; f) A. R. P. M. Valentijn, G. A. van der Marel, L. A. J. M. Sliedregt, T. J. C. van Berkel, E. A. L. Biessen, J. H. van Boom, Tetrahedron 1997, 53, 759-770.
33. For a selection of some recent papers, see: a) U. Sprengard, M. Schudok, W. Schmidt, G. Kretzschmer, H. Kunz, Angew. Chem. Int. Ed. Engl. 1996, 35, 321-324; b) S. A. DeFrees, W. Kosch, W. Way, J. C. Paulson, S. Sabesan, R. L. Halcomb, D.-H. Huang, Y. Ichikawa, C.-H. Wong, J. Am. Chem. Soc. 1995, 117, 66-79; c) E. R. Wijsman, D. Filippov, A. R. P. M. Valentijn, G. A. van der Marel, J. H. van Boom, Rec. Trav. Chim. Pays-Bas 1996, 115, 397-401; d) A. Kichler, F. Schuber, Glycoconj. J. 1995, 12, 275-281; e) J. Lehman, U. P. Weitzel, Carbohydr. Res. 1996, 294, 65-94; f) A. R. P. M. Valentijn, G. A. van der Marel, L. A. J. M. Sliedregt, T. J. C. van Berkel, E. A. L. Biessen, J. H. van Boom, Tetrahedron 1997, 53, 759-770.
34. For a selection of some recent papers, see: a) U. Sprengard, M. Schudok, W. Schmidt, G. Kretzschmer, H. Kunz, Angew. Chem. Int. Ed. Engl. 1996, 35, 321-324; b) S. A. DeFrees, W. Kosch, W. Way, J. C. Paulson, S. Sabesan, R. L. Halcomb, D.-H. Huang, Y. Ichikawa, C.-H. Wong, J. Am. Chem. Soc. 1995, 117, 66-79; c) E. R. Wijsman, D. Filippov, A. R. P. M. Valentijn, G. A. van der Marel, J. H. van Boom, Rec. Trav. Chim. Pays-Bas 1996, 115, 397-401; d) A. Kichler, F. Schuber, Glycoconj. J. 1995, 12, 275-281; e) J. Lehman, U. P. Weitzel, Carbohydr. Res. 1996, 294, 65-94; f) A. R. P. M. Valentijn, G. A. van der Marel, L. A. J. M. Sliedregt, T. J. C. van Berkel, E. A. L. Biessen, J. H. van Boom, Tetrahedron 1997, 53, 759-770.
35. R. T. Lee, Y. C. Lee, in Lectins and Glycobiology (Eds.: H.-J. Gabius and S. Gabius), Springer, Heidelberg, 1993, pp. 9-22.
36. a) W. K. C. Park, S. Aravind, A. Romanowska, J. Renaud, R. Roy, Methods Enzymol. 1994, 42, 294-304;
37. b) R. Roy, Trends in Glycoscience and Glycotechnology 1996, 8, 79-99;
38. c) K. H. Mortell, R. V. Weatherman, L. K. Kiessling, J. Am. Chem. Soc. 1996, 118, 2297-2298.
39. R. Roy, Polymer News 1996, 21, 226-232.
40. a) R. Roy, D. Zanini, S. J. Meunier, A. Romanowska, J. Chem. Soc. Chem. Commun 1993, 1869-1872;
41. b) R. Roy, D. Zanini, S. J. Meunier, A. Romanowska in Am. Chem. Soc. Symp. Ser. Vol. 560, 1994, pp. 104-119.
42. Sialic acid is one of the most important carbohydrate epitopes implicated in many biological processes. For instance, it is a potential anti-inflammatory agent since it acts as an inhibitor of hemagglutination of human erythrocytes by influenza viruses. Having the advantage of well-defined chemical structures and presumably lacking the immunogenisity caused by the non-carbohydrate parts of more conventional macromolecules, glycodendrimers seem to be very attractive candidates for drugs in comparison with multivalent inhibitors based on synthetic polymers or natural proteins, which have been studied previously. See: a) R. Roy, F. O. Andersson, G. Harms, S. Kelm, R. Schauer, Angew. Chem. Int. Ed. Engl. 1992, 31, 1478-1481; b) N. E. Byramova, L. V. Mochalova, I. M. Belyanchikov, M. N. Matrosovich, N. V. Bovin, J. Carhohydr. Chem. 1991, 10, 691-700; c) G. B. Sigal, M. Mammen, G. Dahmann, G. M. Whitesides, J. Am. Chem. Soc. 1996, 118, 1789-3800.
43. Sialic acid is one of the most important carbohydrate epitopes implicated in many biological processes. For instance, it is a potential anti-inflammatory agent since it acts as an inhibitor of hemagglutination of human erythrocytes by influenza viruses. Having the advantage of well-defined chemical structures and presumably lacking the immunogenisity caused by the non-carbohydrate parts of more conventional macromolecules, glycodendrimers seem to be very attractive candidates for drugs in comparison with multivalent inhibitors based on synthetic polymers or natural proteins, which have been studied previously. See: a) R. Roy, F. O. Andersson, G. Harms, S. Kelm, R. Schauer, Angew. Chem. Int. Ed. Engl. 1992, 31, 1478-1481; b) N. E. Byramova, L. V. Mochalova, I. M. Belyanchikov, M. N. Matrosovich, N. V. Bovin, J. Carhohydr. Chem. 1991, 10, 691-700; c) G. B. Sigal, M. Mammen, G. Dahmann, G. M. Whitesides, J. Am. Chem. Soc. 1996, 118, 1789-3800.
44. Sialic acid is one of the most important carbohydrate epitopes implicated in many biological processes. For instance, it is a potential anti-inflammatory agent since it acts as an inhibitor of hemagglutination of human erythrocytes by influenza viruses. Having the advantage of well-defined chemical structures and presumably lacking the immunogenisity caused by the non-carbohydrate parts of more conventional macromolecules, glycodendrimers seem to be very attractive candidates for drugs in comparison with multivalent inhibitors based on synthetic polymers or natural proteins, which have been studied previously. See: a) R. Roy, F. O. Andersson, G. Harms, S. Kelm, R. Schauer, Angew. Chem. Int. Ed. Engl. 1992, 31, 1478-1481; b) N. E. Byramova, L. V. Mochalova, I. M. Belyanchikov, M. N. Matrosovich, N. V. Bovin, J. Carhohydr. Chem. 1991, 10, 691-700; c) G. B. Sigal, M. Mammen, G. Dahmann, G. M. Whitesides, J. Am. Chem. Soc. 1996, 118, 1789-3800.
45. D. Zanini, W. K. C. Park, R. Roy, Tetrahedron Lett. 1995, 36, 7383-7386.
46. D Pagé, D. Zanini, R. Roy, Bioorg. Med. Chem. 1996, 11, 1949-1961.
47. Apart from octavalent dendron 14, homologous dendritic compounds containing 2, 4, and 16 branches have also been used successfully for the attachment of saccharide residues. For more information, see refs. [22] and [24].
48. R. Roy, W. K. C. Park, Q. Wu, S.-N. Wang, Tetrahedron Lett. 1995, 36, 4377-4380.
49. D. Zanini, W. K. C. Park, S. J. Meunier, Q. Wu, S. Aravind, B. Kratzer, R. Roy, Abstr. Am. Chem. Soc. 1995, Vol. 210, Part 2, PMSE 43.
50. D. Zanini. R. Roy, J. Org. Chem. 1996, 61, 7348-7354.
51. X. For ref. see: D. Zanini, R. Roy, Abstracts XVIII International Carbohydrate Symposium (Milan) 1996, BO035.
52. The binding properties of cyclodextrins result from the relatively rigid hydrophobic cavities associated with their cyclic structures. The current state of cvclodextrin chemistry is described in detail in: Comprehensive Supramoleculur Chemistry ; Vol. 3. Cyclodextrins (Eds.: J. Szejtli, T. Osa), Elsevier, Oxford, 1996.
53. a) P. Fügedi, W. Birberg, P. J. Garegg, Å. Pilotti, Carbohydr. Res. 1987, 164, 297-312;
54. b) R. Verduyn, M. Douwes, P. A. M. van der Klein, E. M. Mösinger, G. A. van der Marel, J. H. van Boom, Tetrahedron, 1993, 33, 7301-7316.
55. B. Colonna, M. Sc. Thesis, University of Birmingham, 1996.
56. R. Liang, L. Yan, J. Loebach, M. Ge, Y. Uozumi, K. Sekanina, N. Horan, J. Gildersleeve, C. Thompson, A. Smith, K. Biswas, W. C. Still, D. Kahne, Science 1996, 274, 1520-1522 and references therein;
57. b)see also: C. M. Timmers, J. J. Turner, C. M. Ward, G. A. van der Marel, M. L. C. E. Kouwijzer, P. D. J. Grootenhuis, J. H. van Boom, Chem. Eur. J. 1997, 3, 920-929.
58. H. P. Wessel, C. M. Mitchel, C. M. Lobato, G. Schnidt, Angew, Chem. Int. Ed. Engl. 1995, 34, 2712-2713.
59. X glycomimetics have been developed as suitable inhibitors for the selectin family of adhesion molecules, which are implicated in mediating the attachment of leukocytes at sites of tissue injury and inflammation. See ref. [19a,b];
60. b) For an article on the evolution of carbohydrate drugs, see: S. Borman, Chem. Eng. News 1993, June 28, pp. 27-34.
61. a) T. Toyokuni, A. K. Singhal, Chem. Soc. Rev. 1995, 24, 231-242;
62. b) G. Raghupathi, T. K. Park, S. Zhang, I. J. Kim, L. Graber, S. Adluri, K. O. Lloyd, S. J. Danishefsky, P. O. Livingston, Angew, Chem. Int. Ed. Engl. 1997, 36, 125-128.
63. x (x = 4, 8, 16, 32, 64, ...) = poly(propylene imine) dendrimers; PAMAM dendrimers = poly(amido amine) dendrimers.
64. Note added in proof: The feasibility of using unprotected carbohydrates in dendrimer syntheses has been established very recently. Kieburg and Lindhorst have demonstrated that unprotected carbohydrates, tethered with isothiocyanate functional groups, can readily form thiourea bridges with amine-terminated PAMAM dendrimers (C. Kieburg, T. K. Lindhorst, Tetrahedron Lett. 1997, 38, 3885-3888). In a convergent synthetic approach, we have synthesized some lower-generation carbohydrate-containing dendrimers using unprotected carbohydrates (N. Jayaraman, J. F. Stoddart, Tetrahedron Lett., submitted for publication). The key reaction, which proceeds in DMF/Pyridine (9:1) at 60°C, is one between a three-directional core, carrying N-hydroxysuccinimide ester functions, and free glucoside and mannoside-containing dendritic wedges with amino groups at their focal points. The development of synthetic routes utilizing unprotected carbohydrates to prepare dendrimers has the advantages that i) it circumvents steric inhibition caused by the presence of protecting groups on the saccharide residues in a growing dendrimer and ii) it avoids the consequent reduction in the surface densities of the final free saccharide-containing dendrimers upon removal of the protecting groups. The absence of any protecting groups on the peripheral glycoside units should now make it possible to prepare large densely-packed carbohydrate-containing dendrimers without the need to resort to protecting group manipulations on the saccharide residues.
65. Note added in proof: The feasibility of using unprotected carbohydrates in dendrimer syntheses has been established very recently. Kieburg and Lindhorst have demonstrated that unprotected carbohydrates, tethered with isothiocyanate functional groups, can readily form thiourea bridges with amine-terminated PAMAM dendrimers (C. Kieburg, T. K. Lindhorst, Tetrahedron Lett. 1997, 38, 3885-3888). In a convergent synthetic approach, we have synthesized some lower-generation carbohydrate-containing dendrimers using unprotected carbohydrates (N. Jayaraman, J. F. Stoddart, Tetrahedron Lett., submitted for publication). The key reaction, which proceeds in DMF/Pyridine (9:1) at 60°C, is one between a three-directional core, carrying N-hydroxysuccinimide ester functions, and free glucoside and mannoside-containing dendritic wedges with amino groups at their focal points. The development of synthetic routes utilizing unprotected carbohydrates to prepare dendrimers has the advantages that i) it circumvents steric inhibition caused by the presence of protecting groups on the saccharide residues in a growing dendrimer and ii) it avoids the consequent reduction in the surface densities of the final free saccharide-containing dendrimers upon removal of the protecting groups. The absence of any protecting groups on the peripheral glycoside units should now make it possible to prepare large densely-packed carbohydrate-containing dendrimers without the need to resort to protecting group manipulations on the saccharide residues.