Synthesis of diverse and complex molecules on the solid phase

Accounts of Chemical Research

Volumn 33, Issue 4, 2000, Pages 215-224

  Wendeborn, Sebastian ^a   De Mesmaeker, Alain ^a   Brill, Wolfgang K D ^a   Berteina, Sabine ^a  

^a NOVARTIS PHARMA AG   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

ACETYLENE DERIVATIVE; ARSINE DERIVATIVE; BORONIC ACID DERIVATIVE; PALLADIUM; POLYSTYRENE; THIOL DERIVATIVE;

ANIMAL; ARTICLE; CYCLIZATION; DERIVATIZATION; HUMAN; ORGANIC CHEMISTRY; REACTION ANALYSIS; SOLID STATE; SYNTHESIS;

ANIMALS; CHEMISTRY, ORGANIC; CYCLIZATION; HUMANS; PALLADIUM;

EID: 0034007951     PISSN: 00014842     EISSN: None     Source Type: Journal    
DOI: 10.1021/ar990100d     Document Type: Article

References (82)

1. (a) Dörner, B.; Blondelle, S. E.; Pinilla, C.; Appel, J.; Dooley, C. T.; Eicher, J.; Ostresh, J. M.; Perez-Paya, E.; Houghten, R. A. In Combinatorial Libraries Synthesis, Screening and Application Potential; Cortese, R., Ed.; Walter de Gruyter & Co.: New York, 1996; pp 1-25.
2. (b) Gallop, M. A.; Barrett, R. W.; Dower, W. J.; Fodor, S. P. A.; Gordon, E. M. Applications of combinatorial technologies to drug discovery. 1. Background and peptide combinatorial libraries. J. Med. Chem. 1994, 37, 1233.
3. (c) Gordon, E. M.; Barrett, R. W.; Dower, W. J.; Fodor, S. P. A.; Gallop, M. A. Applications of combinatorial technologies to drug discovery. 2. Combinatorial organic synthesis, library screening strategies, and future directions. J. Med. Chem. 1994, 37, 1385.
4. (d) Früchtel, J. S.; Jung, G. Organic chemistry on solid supports. Angew. Chem., Int. Ed. Engl. 1996, 35, 17.
5. (e) Thompson, L. A.; Ellman, J. A. Synthesis and applications of small molecule libraries. Chem. Rev. 1996, 96, 555.
6. (f) Balkenhohl, F.; v. d. Bussche-Hünnefeld, C.; Lansky, A.; Zechel, C. Combinatorial synthesis of small organic molecules. Angew. Chem., Int. Ed. Engl. 1996, 35, 2288.
7. (g) Hermkens, P. H. H.; Ottenheijm, H. C. J.; Rees, D. Solid-phase organic reactions: a review of the recent literature. Tetrahedron 1996, 52, 4527.
8. (h) Hermkens, P. H. H.; Ottenheijm, H. C. J.; Rees, D. C. Solid-phase organic reactions II: a review of the recent literature Nov 95-Nov 96. Tetrahedron 1997, 53, 5643.
9. Booth, S.; Hermkens, P. H. H.; Ottenheijm, H. C. J.; Rees, D. C. Solid-phase organic reactions III: a review of the literature Nov 96-Dec 97. Tetrahedron 1998, 54, 15385.
10. (j) Corbett, J. W. Recent progress in solid-phase heterocycle syntheses. A review. Org. Prepr. Proc. Int. 1998, 30, 489.
11. (k) Lorsbach, B. A.; Kurth, M. J. Carbon-carbon bond forming solid-phase reactions. Chem. Rev. 1999, 99, 1549.
12. Merrifield, R. B. Solid-phase peptide synthesis. 1. The synthesis of a tetrapeptide. J. Am. Chem. Soc. 1963, 85, 2149.
13. Geysen, H. M.; Meloen, R. H.; Barteling, S. J. Use of peptide synthesis to probe viral antigens for epitopes to a resolution of a single amino acid. Proc. Natl. Acad. Sci. U.S.A. 1984, 81, 3998.
14. Houghten, R. A. General method for the rapid solid-phase synthesis of large numbers of peptides: specificity of antigen-antibody interaction at the level of individual amino acids, Proc. Natl. Acad. Sci. U.S.A. 1985, 82, 5131.
15. (a) Furka, A.; Sebestyen, F.; Asgedom, M.; Dibo, G. General method for rapid synthesis of multicomponent peptide mixtures. Int. J. Pept. Protein Res. 1991, 37, 487.
16. (b) Sebestyen, F.; Dibo, G.; Kovacs, A.; Furka, A. Chemical synthesis of peptide libraries. Bioorg. Med. Chem. Lett. 1993, 3, 413.
17. (c) Furka, A. History of combinatorial chemistry. Drug. Dev. Res. 1995, 36, 1.
18. (a) Merrifield, R. B. Solid-phase synthesis. Science 1986, 232, 341.
19. (b) Eichler, J.; Appel, J. R.; Blondelle, S. E.; Dooley, C. T.; Dörner, B.; Ostresh, J. M.; Perez-Paya, E.; Pinilla, C.; Houghten, R. A. Peptide, peptidomimetic, and organic synthetic combinatorial libraries. Med. Res. Rev. 1995, 15, 481.
20. (a) Giannis, A.; Kolter, T. Peptidomimetics for receptor ligands-discovery, development, and medicinal perspectives. Angew. Chem., Int. Ed. Engl. 1993, 32, 1244.
21. (b) Liskamp, R. M. J. A new application of modified peptides and peptidomimetics: potential anticancer agents. Angew. Chem., Int. Ed. Engl. 1994, 33, 305.
22. (c) Dörner, B.; Husar, G. M.; Ostresh, J. M.; Houghten, R. A. The synthesis of peptidomimetic combinatorial libraries through successive amide alkylations. Bioorg. Med. Chem. 1996, 4, 709.
23. (d) Ostresh, J. M.; Blondelle, S. E.; Dörner, B.; Houghten, R. A. Generation and use of nonsupport-bound peptide and peptidomimetic combinatorial libraries. Methods Enzymol. 1996, 267, 220.
24. Wyatt, J. R.; Vickers, T. A.; Roberson, J. L.; Buckheit, R. W., Jr.; Klimkait, T.; Debaets, E.; Davis, P. W.; Rayner, B.; Imbach, J. L.; Ecker, D. J. Combinatorially selected guanosine-quartet structure is a potent inhibitor of human immunodeficiency virus envelope-mediated cell fusion. Proc. Natl. Acad. Sci. U.S.A. 1994, 91, 1356.
25. (a) Douglas, S. P.; Whitfield, D. M.; Krepinsky, J. J. Polymer-supported solution synthesis of oligosaccharides using a novel versatile linker for the synthesis of D-mannopentaose, a structural unit of D-mannans of pathogenic yeasts. J. Am. Chem. Soc. 1995, 117, 2116.
26. (b) Schuster, M.; Wang, P.; Paulson, J. C.; Wong, C.-H. Solid-phase chemical-enzymatic synthesis of glycopeptides and oligosaccharides. J. Am. Chem. Soc. 1994, 116, 1135.
27. (c) Frechet, J. M.; Schuerch, C. Solid-phase synthesis of oligosaccharides. 1. Preparation of the solid support. Poly[p-(1-propen-3-ol-1-yl)-styrene]. J. Am. Chem. Soc. 1971, 93, 492.
28. (a) Leznoff, C. C.; Sywanyk, W. Use of insoluble polymer supports in organic synthesis. 9. Synthesis of unsymmetrical carotenoids on solid phases. J. Org. Chem. 1977, 42, 3203.
29. (b) Leznoff, C. C.; Wong, J. Y. The Use of polymer supports in organic synthesis. III. Selective chemical reactions on one aldehyde group of symmetrical dialdehydes. Can. J. Chem. 1973, 51, 3756.
30. (c) Wong, J. Y.; Leznoff, C. C. The use of polymer supports in organic synthesis. II. The syntheses of monoethers of symmetrical diols. Can. J. Chem. 1973, 51, 2452.
31. Leznoff, C. C. The use of insoluble polymer supports in general organic synthesis. Acc. Chem. Res. 1978, 11, 327.
32. Crowley, J. I.; Rapoport, H. Solid-phase organic synthesis: novelty or fundamental concept? Acc. Chem. Res. 1976, 9, 135.
33. Bunin, B. A.; Ellman, J. A. A general and expedient method for the solid-phase synthesis of 1,4-benzodiazepine derivatives. J. Am. Chem. Soc. 1992, 114, 10997.
34. (a) Nicolaou, K. C.; Winssinger, N.; Pastor, J.; Ninkovic, S.; Sarabia, F.; He, Y.; Vourloumis, D.; Yang, Z.; Li, T.; Giannakakou, P.; Hamel, E. Synthesis of epothilones A and B in solid and solution phase. Nature 1996, 387, 268.
35. (b) Nicolaou, K. C.; Vourloumis, D.; Li, T.; Pastor, J.; Winssinger, N.; He, Y.; Ninkovic, S.; Sarabia, F.; Vallberg, H.; Roschangar, F.; King, N. P.; Finlay, M. R. V.; Giannakakou, P.; Verdier-Pinard, P.; Hamel, E. Designed epothilones: combinatorial synthesis, tubulin assembly properties, and cytotoxic action against taxol-resistant tumor cells. Angew. Chem., Int. Ed. Engl. 1997, 36, 2097.
36. (c) Tan, D. S.; Foley, M. A.; Shair, M. D.; Schreiber, S. L. Stereoselective synthesis of over two million compounds having structural features both reminiscent of natural products and compatible with miniaturized cell-based assays. J. Am. Chem. Soc. 1998, 120, 8565.
37. For Stille couplings, see: (a) Forman, F. W.; Sucholeiki, I. Solid-phase synthesis of biaryls via the Stille reaction. J. Org. Chem. 1995, 60, 523.
38. (b) Plunkett, M. J.; Ellman, J. A. Solid-phase synthesis of structurally diverse 1,4-benzodiazepine derivatives using the Stille coupling reaction. J. Am. Chem. Soc. 1995, 117, 3306.
39. (c) Deshpande, M. S. Formation of carbon-carbon bond on solid support: application of the Stille reaction. Tetrahedron Lett. 1994, 35, 5613. For Suzuki couplings, see:
40. (d) Backes, B. J.; Ellman, J. A. Carbon-carbon bond-forming methods on solid support. Utilization of Kenner's "Safety-Catch" Linker. J. Am. Chem. Soc. 1994, 116, 11171.
41. (e) Piettre, S. R.; Baltzer, S. A new approach to the solid-phase Suzuki coupling reaction. Tetrahedron Lett. 1997, 38, 1197.
42. (f) Yoo, S.; Seo, J.; Yi, K., Gong, Y. Solid-phase synthesis of biphenyltetrazole darivatives. Tetrahedron Lett. 1997, 38, 1203. For Heck reactions, see:
43. (g) Yu, K.-L.; Deshpande, M. S.; Vyas, D. M. Heck reactions in solid-phase synthesis. Tetrahedron Lett. 1994, 35, 8919.
44. (h) Hiroshige, M.; Hauske, J. R.; Zhou, P. Formation of C-C bond in solid-phase synthesis using the Heck reaction. Tetrahedron Lett. 1995, 36, 4567. For others, see:
45. (i) Young, J. K.; Nelson, J. C.; Moore, J. S. Synthesis of sequence specific phenylacetylene oligomers on an insoluble solid support. J. Am. Chem. Soc. 1994, 116, 10841. For use of polymer bound Pd catalyst, see:
46. (j) Jang, S.-B. Polymer-bound palladium-catalyzed cross-coupling of organoboron compounds with organic halides and organic triflates. Tetrahedron Lett. 1997, 38, 1793.
47. In most examples (ref 2), much more reactive electron-poor aromatic halides are used in the Pd-coupling reactions.
48. (a) Wendeborn, S.; Berteina, S.; Brill, W. K.-D.; De Mesmaeker, A. Pd-Mediated C-C and C-S bond formation on solid support: a scope and limitation study. Synlett 1998, 671.
49. (b) Berteina, S.; Wendeborn, S.; Brill, W. K.-D.; De Mesmaeker, A. Pd-Mediated C-C bond formation with olefins and acetylenes on solid support: a Scope and Limitation Study. Synlett 1998, 676.
50. Double couplings imply complete removal of all reagents and side products through washing of the resin before submitting it under identical coupling conditions for a second time. If the washing step is avoided, no significantly increased yields were observed, presumably due to accumulation of catalyst poisoning side products.
51. Kwon, H. B.; McKee, B. H.; Stille, J. K. Palladium-catalyzed coupling reactions of (α-ethoxyvinyl)trimethylstannane with vinyl and aryl triflates. J. Org. Chem. 1990, 55, 3114.
52. (a) Farina, V.; Krishnan, B. Large rate accelerations in the Stille reaction with tri-2-furylphosphine and triphenylarsine as palladium ligands: mechanistic and synthetic implications. J. Am. Chem. Soc. 1991, 113, 9585.
53. (b) Aliprantis, A. O.; Canary, J. W. Observation of catalytic intermediates in the Suzuki reaction by electrospray mass spectrometry. J. Am. Chem. Soc. 1994, 116, 6985.
54. (a) Kosugi, M.; Shimizu, T.; Migita, T. Reactions of aryl halides with thiolate anions in the presence of catalytic amounts of tetrakis(triphenylphosphine)palladium. Preparation of aryl sulfides. Chem. Lett. 1978, 13.
55. (b) Migita, T.; Shimizu, T.; Asami, Y.; Shiobara, J.; Kato, Y.; Kosugi, M. The palladium catalyzed nucleophilic substitution of aryl halides by thiolate anions. Bull. Chem. Soc. Jpn. 1980, 53, 1385.
56. (c) Ciattini, P. G.; Morera, E.; Ortar, G. A new, palladium-catalyzed synthesis of aromatic mercapturic acid derivatives. Tetrahedron Lett. 1995, 36, 4133.
57. (d) Rajagopalan, S.; Radke, G.; Evans, M.; Tomich, J. M. Synthesis of N-t-Boc-4-S-t-butyl-L-thiophenylalanine via palladium catalyzed cross-coupling reaction of N-t-Boc-4-iodo-L-phenylalanine with t-butylthiol or sodium t-butylthiolate. Synth. Commun. 1996, 26, 1431.
58. (a) de Meijere, A.; Meyer, F. E. Fine feathers make fine birds: the Heck reaction in modern garb. Angew. Chem., Int. Ed. Engl. 1994, 33, 2379.
59. (b) Heck, R. F. Palladium Reagents in Organic Syntheses; Academic Press: London, 1985,
60. (c) Dieck, H. A.; Heck, F. R. Palladium catalyzed synthesis of aryl, heterocyclic, and vinylic acetylene derivatives. J. Organomet. Chem. 1975, 93, 259.
61. (a) Heck, R. F. Palladium-catalyzed vinylation of organic halides. Org. React. 1982, 27, 345.
62. (b) Heck, R. F. Vinyl substitutions with organopalladium intermediates. In Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon Press: New York, 1991; Vol. 4, p 833.
63. For previous Heck reactions on the solid phase, see ref 3a and the following: (a) Hiroshige, M.; Hauske, J. R.; Zhou, P. Formation of C-C bond in solid-phase synthesis using the Heck reaction. Tetrahedron Lett. 1995, 36, 4567. For an intramolecular Heck reactions on the solid phase, see:
64. (b) Goff, D. A.; Zuckermann, R. N. Solid-phase synthesis of highly substituted peptoid 1(2H)-isoquinolinones. J. Org. Chem. 1995, 60, 5748.
65. (c) Yun W.; Mohan, R. Heck reaction on solid support: synthesis of indole analogues. Tetrahedron Lett. 1996, 37, 7189.
66. Berteina, S.; De Mesmaeker, A. Application of radical chemistry to solid support synthesis. Tetrahedron Lett. 1998, 39, 5759.
67. For radical cyclizations on solid by others, see: (a) Routledge, A.; Abell, C.; Balasubramanian, S. An investigation into solid-phase radical chemistry-synthesis of furan rings. Synlett 1997, 61.
68. 2-mediated radical cyclization. J. Org. Chem. 1997, 62, 5678.
69. tBu: Schwesinger, R.; Schlemper, H. Peralkylated polyaminophosphazenes-extremely strong, neutral nitrogen bases. Angew. Chem., Int. Ed. Engl. 1987, 26, 1167.
70. Berteina, S.; Wendeborn, S.; De Mesmaeker, A. Radical and palladium-mediated cyclizations of ortho-iodo benzyl enamines: Application to solid-phase synthesis. Synlett 1998, 1231.
71. (a) Hudlicky, T.; Thorpe, A. J. Current status and future perspectives of cyclohexadiene-cis-diols in organic synthesis: versatile intermediates in the concise design of natural products. Chem. Commun. 1996, 1993.
72. (b) Carless, H. A. J. The use of cyclohexa3,5-diene-1,2-diols in enantiospecific synthesis. Tetrahedron Asymmetry 1992, 3, 795.
73. (c) Hudlicky, T.; Luna, H.; Olivo, H. F.; Andersen, C.; Nugent, T.; Price, J. D. Biocatalysis at the strategy of choice in the exhaustive enantiomerically controlled synthesis of conduritols. J. Chem. Soc., Perkin. Trans. 1 1991, 2907.
74. (d) Ley, S. V.; Redgrave, A. J.; Taylor, S. C.; Ahmed, S.; Ribbons, D. W. Microbial oxidation in synthesis: preparation of novel 3-substituted cis-cyclohexa-3,5-diene-1,2-diol derivatives from (1S.2S)-3-bromocyclohexa-3,5-diene-1,2-diol. Synlett 1991, 741.
75. (e) Ley, S. V.; Sternfeld, F. Microbial oxidation in synthesis: preparation of (+)- and (-)-pinitol from benzene. Tetrahedron 1989, 45, 3463.
76. 3) and related derivatives. Tetrahedron Lett. 1988, 23, 5305.
77. (g) Ley, S. V.; Sternfeld, F.; Taylor, S. Microbial oxidation in synthesis: A six step preparation of (±)-pinitol from benzene. Tetrahedron Lett. 1987, 28, 225.
78. Wendeborn, S.; De Mesmaker, A.; Brill, W. K.-D. Polymer-bound 3,5-cyclohexadiene-1,2-diols as core structures for the development of small molecule libraries. Synlett 1998, 865.
79. Murray, R. W.; Jeyaraman, R. Dioxiranes: synthesis and reactions of methyldioxiranes. J. Org. Chem. 1985, 50, 2847.
80. Berteina, S.; De Mesmaeker, A. Wendeborn, S. Functionalization via radical cyclization of cyclohexenediol derivatives bound to polystyrene. Synlett 1999, 1121.
81. Brill, W. K.-D.; De Mesmaeker, A.; Wendeborn, S. Solid-phase synthesis of levoglucosan derivatives. Synlett 1998, 1085.
82. Frenette, R.; Friesen, R. W. Biaryl synthesis via Suzuki coupling on a solid support. Tetrahedron Lett. 1994, 35, 9177.