Synthesis of 12 Stereochemically and Structurally Diverse C-Trisaccharides

Journal of Organic Chemistry

Volumn 62, Issue 16, 1997, Pages 5267-5283

  Sutherlin, Daniel P ^a   Armstrong, Robert W ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 0001199729     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo9621534     Document Type: Article

References (132)

1. (a) Varki, A. Glycobiology 1993, 3, 97-130.
2. (b) Feizi, T. Curr. Opin. Struct. Bio. 1993, 3, 701.
3. (c) Varki, A. Proc. Natl. Acad. Sci. U.S.A. 1994, 91, 7390.
4. (d) Opdenakker, G.; Rudd, P. M.; Ponting, C. P.; Dwek, R. FASEB J. 1993, 7, 1330.
5. (a) Gyler, M.; Rose, D.; Bundle, D. Science 1991, 253, 442.
6. (b) Boren, T.; Falk, P.; Roth, K. A.; Larson, G.; Normark, S. Science 1993, 262, 1892.
7. (a) Paulson, J. C. The Receptors; Academic: New York, 1985; Vol. 2.
8. (b) Wharton, S. A.; Weis, W.; Skehel, J. J.; Wiley, D. C. The Influenza Virus; Plenum; New York, 1989.
9. (a) Phillips, M. L.; Nudelman, E.; Gaeta, F. C. A.; Perez, M.; Sinhal, A. K.; Hakomori, S.; Paulson, J. C. Science 1990, 250, 1130.
10. (b) Higashi, H.; Hirabayashi, Y.; Fukui, Y.; Naiki, M.; Matsumoto, M.; Ueda, S.; Kato, S. Cancer Res. 1985, 45, 3796-3802.
11. (c) Muramatsu, T. Glycobiology 1993, 3, 298.
12. (d) Hiraizumi, S.; Takasaki, S.; Ohuchi, N.; Harada, Y.; Nose, M.; Mori, S.; Kobata, A. J. Cancer Res. 1992, 83, 1063.
13. (a) Butcher, E. C. Am. J. Path. 1990, 1, 3-11.
14. (b) Walz, G.; Aruffo, A.; Kolanus, W.; Polley, M. J.; Phillips, M. L.; Wagner, E.; Nudelman, E.; Sinhal, A. K.; Hakomori, S.; Paulson, J. C. Proc. Natl. Acad. Sci. U.S.A. 1991, 88, 6224.
15. Sutherlin, D. P.; Hughes R.; Stark, T. M.; Armstrong, R. W. J. Org. Chem. 1996, 61, 8350.
16. Armstrong, R. W.; Sutherlin, D. P. Tetrahedron Lett. 1994, 35, 7743.
17. Sutherlin, D. P.; Armstrong, R. W. J. Am. Chem. Soc. 1996, 118, 9802.
18. (a) Gallop, M. A.; Barrett, R. W.; Dower, W. J.; Fodor, S. P. A.; Gordon, E. M. J. Med. Chem. 1994, 37, 1233-1251.
19. (b) Gordon, E. M.; Barrett, R. W.; Dower, W. J.; Fodor, S. P. A.; Gallop, M. A. J. Med. Chem. 1994, 37, 1385-1401.
20. While only a fraction of the 5000 possible disaccharides occur in nature, the diversity pool nonetheless is of great interest.
21. Thompson, L. A.; Ellman, J. A. Chem. Rev. 1996, 96, 555.
22. Another obstacle associated with cell surface carbohydrates is their low affinities for the protein receptors that bind them. This has been addressed by presenting multivalent ligands through the use of a variety of structural templates. For an overview of the progress in this area, see: Kiessling, L. L.; Pohl, N. L. Chem. Biol. 1996, 3, 71.
23. (a) Frechet, J. M.; Schuerch, C. J. Am. Chem. Soc. 1972, 95, 604.
24. (b) Frechet, J. M.; Schuerch, C. Carbohydr. Res. 1972, 22, 399.
25. (c) Guthrie, R. D.; Jenkins, A. D.; Roberts, G. A. F. J. Chem. Soc., Perkin Trans. 1 1973, 2414.
26. (a) Douglas, S. P.; Whitfield, D. M.; Krepinski, J. J. J. Am. Chem. Soc. 1995, 117, 2116.
27. (b) Krepinski, J. J.; Douglas, S. P.; Whitfield, D. M. Methods Enzymol. 1994, 242, 280.
28. (c) Adinolfi, M.; Barone, G.; De Napoli, L.; Iadonisi, A.; Piccialli, G. Tetrahedron Lett. 1996, 37, 5007.
29. (a) Van, L.; Taylor, C. M.; Goodnow, R., Jr.; Kahne, D. J. Am. Chem. Soc. 1994, 116, 6953.
30. (b) Wang, Y.; Zhang, H.; Voelter, W. Chem. Lett. 1995, 273.
31. (c) Liang, R.; Yan, L.; Loebach, J.; Ge, M.; Uozumi, Y.; Sekanina, K.; Horan, N.; Gildersleeve, J.; Thompson, C.; Smith, A.; Biswas, K; Still, W. C.; Kahne, D. Science 1996, 274, 1520.
32. Nicolaou, K. C.; Winssinger, N.; Pastor, J.; DeRoose, F. J. Am. Chem. Soc. 1997, 119, 449.
33. (a) Wong, C.-H.; Schuster, M.; Wang, P.; Sears, P. J. Am. Chem. Soc. 1993, 115, 5893.
34. (b) Schuster, M.; Wang, P.; Paulson, J. C.; Wong, C.-H. J. Am. Chem. Soc. 1994, 116, 1135.
35. (c) Meldal, M.; Auzanneau, F.-I.; Hindsgaul, O.; Palcic, M. M. J. Chem. Soc., Chem. Commun. 1994, 1849.
36. (a) Christiansen-Brams, I.; Meldal, M.; Bock, K. J. Chem. Soc., Perkin Trans. 1 1993, 1461.
37. (b) Jensen, K. J.; Meldal, M.; Bock, K. J. Chem. Soc., Perkin Trans. 1 1993, 2119.
38. (c) Meldal, M.; Bock, K. Glycoconjugate J. 1994, 11, 59.
39. (d) Seitz, O.; Kunz, H. Angew. Chem., Int. Ed. Engl. 1995, 34, 803.
40. (d) Rio-Anneheim, S.; Paulsen, H.; Meldal, M.; Bock, K. J. Chem. Soc., Perkin Trans. 1 1995, 1071.
41. (e) Reimer, K. B.; Meldal, M.; Shoichi, K.; Fukase, K.; Bock, K J. Chem. Soc., Perkin Trans. 1 1993, 925.
42. (f) Broddefalk, J.; Bergquist, K. E.; Kihlberg, J. Tetrahedron Lett. 1996, 37, 3011.
43. (a) Cohen-Anisfeld, S. T.; Lansbury, P. T., Jr. J. Am. Chem. Soc. 1993, 115, 10531.
44. (b) Vetter, D.; Gallop, M. A. Bioconjugate Chem. 1995, 6, 316.
45. (c) Vetter, D. et al. Angew. Chem., Int. Ed. Engl. 1995, 34, 60.
46. (d) Roberge, J. Y.; Beebe, X.; Danishefsky, S. J. Science 1995, 269, 202.
47. (a) Randolph, J. T.; McClure, K. F.; Danishefsky, S. J. J. Am. Chem. Soc. 1995, 117, 5712.
48. (b) Randolph, J. T.; Danishefsky, S. J. Angew. Chem., Int. Ed. Engl. 1994, 33, 1470.
49. (c) Danishefsky, S. J.; et al. Science 1993, 260, 1307.
50. The topics in this paragraph have been reviewed in more detail. Sofia, M. J. Drug Discovery Today 1996, 1, 27.
51. (a) Armstrong, R. W.; Sutherlin, D. P.; Wolinski, L. Presented at the 31st Annual Western Regional Meeting of the American Chemical Society, San Diego, CA, October 18-21, 1995.
52. (b) Rao, N. N. Presented at the 31st Annual Western Regional Meeting of the American Chemical Society, San Diego, CA, October 18-21, 1995.
53. (c) Uchiyama, T.; Vassilev, V.; Kajimoto, T.; Wong, W.; Lin, C.-C.; Huang, H.; Wong, C.-H. J. Am. Chem. Soc. 1995, 117, 5396.
54. (d) Huryn, D. Presented at the 31st Annual Western Regional Meeting of the American Chemical Society, San Diego, CA, October 18-21, 1995.
55. (e) For a review, see: Bertozzi, C. R. Chem. Biol. 1995, 11, 703-708. (f) Kogan, T. P.; Dupre, B.; Keller, K. M.; Scott, I. L.; Bui, H.; Market, R. V.; Beck, P. J.; Voytus, J. A.; Revelle, B. M.; Scott, D. J. Med. Chem. 1995, 38, 4976-4984. (g) Wu, S.-H.; Shimazaki, M.; Lin, C.-C.; Moree, W. J.; Weitz-Schmidt, G.; Wong, C.-H. Angew. Chem., Int. Ed. Engl. 1996, 35, 88. (h) Lin, C.-C.; Shimazaki, M.; Heck, M.-P.; Aoki, S.; Wang, R.; Kimura, T.; Ritzen, H.; Takayama, S.; Wu, S.-H.; Weitz-Schmidt, G.; Wong, C.-H. J. Am. Chem. Soc. 1996, 118, 6826. (i) Park, W. K. C.; Auer, M.; Jaksche, H.; Wong, C.-H. J. Am. Chem. Soc. 1996, 118, 10150.
56. (e) For a review, see: Bertozzi, C. R. Chem. Biol. 1995, 11, 703-708. (f) Kogan, T. P.; Dupre, B.; Keller, K. M.; Scott, I. L.; Bui, H.; Market, R. V.; Beck, P. J.; Voytus, J. A.; Revelle, B. M.; Scott, D. J. Med. Chem. 1995, 38, 4976-4984. (g) Wu, S.-H.; Shimazaki, M.; Lin, C.-C.; Moree, W. J.; Weitz-Schmidt, G.; Wong, C.-H. Angew. Chem., Int. Ed. Engl. 1996, 35, 88. (h) Lin, C.-C.; Shimazaki, M.; Heck, M.-P.; Aoki, S.; Wang, R.; Kimura, T.; Ritzen, H.; Takayama, S.; Wu, S.-H.; Weitz-Schmidt, G.; Wong, C.-H. J. Am. Chem. Soc. 1996, 118, 6826. (i) Park, W. K. C.; Auer, M.; Jaksche, H.; Wong, C.-H. J. Am. Chem. Soc. 1996, 118, 10150.
57. (e) For a review, see: Bertozzi, C. R. Chem. Biol. 1995, 11, 703-708. (f) Kogan, T. P.; Dupre, B.; Keller, K. M.; Scott, I. L.; Bui, H.; Market, R. V.; Beck, P. J.; Voytus, J. A.; Revelle, B. M.; Scott, D. J. Med. Chem. 1995, 38, 4976-4984. (g) Wu, S.-H.; Shimazaki, M.; Lin, C.-C.; Moree, W. J.; Weitz-Schmidt, G.; Wong, C.-H. Angew. Chem., Int. Ed. Engl. 1996, 35, 88. (h) Lin, C.-C.; Shimazaki, M.; Heck, M.-P.; Aoki, S.; Wang, R.; Kimura, T.; Ritzen, H.; Takayama, S.; Wu, S.-H.; Weitz-Schmidt, G.; Wong, C.-H. J. Am. Chem. Soc. 1996, 118, 6826. (i) Park, W. K. C.; Auer, M.; Jaksche, H.; Wong, C.-H. J. Am. Chem. Soc. 1996, 118, 10150.
58. (e) For a review, see: Bertozzi, C. R. Chem. Biol. 1995, 11, 703-708. (f) Kogan, T. P.; Dupre, B.; Keller, K. M.; Scott, I. L.; Bui, H.; Market, R. V.; Beck, P. J.; Voytus, J. A.; Revelle, B. M.; Scott, D. J. Med. Chem. 1995, 38, 4976-4984. (g) Wu, S.-H.; Shimazaki, M.; Lin, C.-C.; Moree, W. J.; Weitz-Schmidt, G.; Wong, C.-H. Angew. Chem., Int. Ed. Engl. 1996, 35, 88. (h) Lin, C.-C.; Shimazaki, M.; Heck, M.-P.; Aoki, S.; Wang, R.; Kimura, T.; Ritzen, H.; Takayama, S.; Wu, S.-H.; Weitz-Schmidt, G.; Wong, C.-H. J. Am. Chem. Soc. 1996, 118, 6826. (i) Park, W. K. C.; Auer, M.; Jaksche, H.; Wong, C.-H. J. Am. Chem. Soc. 1996, 118, 10150.
59. (e) For a review, see: Bertozzi, C. R. Chem. Biol. 1995, 11, 703-708. (f) Kogan, T. P.; Dupre, B.; Keller, K. M.; Scott, I. L.; Bui, H.; Market, R. V.; Beck, P. J.; Voytus, J. A.; Revelle, B. M.; Scott, D. J. Med. Chem. 1995, 38, 4976-4984. (g) Wu, S.-H.; Shimazaki, M.; Lin, C.-C.; Moree, W. J.; Weitz-Schmidt, G.; Wong, C.-H. Angew. Chem., Int. Ed. Engl. 1996, 35, 88. (h) Lin, C.-C.; Shimazaki, M.; Heck, M.-P.; Aoki, S.; Wang, R.; Kimura, T.; Ritzen, H.; Takayama, S.; Wu, S.-H.; Weitz-Schmidt, G.; Wong, C.-H. J. Am. Chem. Soc. 1996, 118, 6826. (i) Park, W. K. C.; Auer, M.; Jaksche, H.; Wong, C.-H. J. Am. Chem. Soc. 1996, 118, 10150.
60. Kanie, O.; Barresi, F.; Ding, Y.; Labbe, J.; Otter, A.; Forsberg, L. S.; Ernst, B.; Hindsgaul, O. Angew. Chem., Int. Ed. Engl. 1995, 34, 2720.
61. (a) Tschamber, T.; Backenstrass, F.; Nueburger, M.; Zehnder, M.; Streith, J. Tetrahedron 1994, 50, 1135.
62. (b) Kobayashi, S.; Kawasuji, T. Synth. Lett. 1993, 911.
63. (c) Ko, S. Y.; Lee, W. M.; Masamune, S.; Reed, III, L. A.; Sharpless, K. B.; Walker, F. J. Tetrahedron 1990, 46, 245.
64. (d) Mukaiyama, T.; Suzuki, K.; Yamada, T.; Tabusa, F. Tetrahedron 1990, 46, 265.
65. (e) McGarvey, G. J.; Kimura, M.; Oh, T. J. Carbohydr. Chem. 1984, 3, 125.
66. (f) Hudlicky, T.; Entwistle, D. A.; Pitzer, K. K.; Thorpe, A. J. Chem. Rev. 1996, 96, 1195.
67. (g) Goebel, M.; Ugi, I. Tetrahedron Lett. 1995, 36, 6043.
68. (h) Roush, W. R.; Gustin, D. Tetrahedron Lett. 1994, 35, 4931.
69. (h) Hudlicky, T.; Abboud, K. A.; Entwistle, D. A.; Fan, R.; Maurya, R.; Thorpe, A. J.; Bolonick, J.; Myers, B. Synthesis 1996, 897.
70. (a) Lemieux, R. U.; Du, M.-H.; Spohr, U. J. Am. Chem. Soc. 1994, 116, 9803.
71. (b) Lemieux, R. U.; Du, M.-H.; Spohr, U.; Acharya, S.; Surolia, A. Can. J. Chem. 1994, 72, 158.
72. (a) Lowary, T. L.; Hindsgaul, O. Carbohydr. Res. 1993, 249, 163.
73. (b) Khan, S. H.; Crawley, S. C.; Kanie, O.; Hindsgaul, O. J. Biol. Chem. 1993, 268, 2468.
74. (a) Haneda, T.; Goekjian, P.; Kim, S. H.; Kishi, Y. J. Org. Chem. 1992, 57, 490.
75. (b) Wei, A.; Haudrechy, A.; Audin, C.; Jun, H.-S.; Haudrechy-Bretel, N.; Kishi, Y. J. Org. Chem. 1995, 60, 2160.
76. (c) Wei, A.; Boy, K. M.; Kishi, Y. J. Am. Chem. Soc. 1995, 117, 9432.
77. (a) Wang, Y.-F.; Takaoka, Y.; Wong, C.-H. Angew. Chem., Int. Ed. Engl. 1994, 33, 1242.
78. (b) Sinnott, M. L. Chem. Rev. 1990, 90, 1171.
79. (c) Winchester, B.; Fleet, G. W. Glycobiology 1992, 2, 199.
80. (d) Look, G. C.; Fotsch, C. H.; Wong, C. H. Acc. Chem. Res. 1993, 26, 182.
81. (a) Henderson, I.; Sharpless, K. B.; Wong, C.-H. J. Am. Chem. Soc. 1994, 116, 558.
82. (b) Wong, C.-H.; Halcomb, R. L.; Ichikawa, Y.; Kajimoto, T. Angew. Chem., Int. Ed. Engl. 1995, 34, 412.
83. (c) Harrie, J. M.; Qiao, L.; Fitz, W.; Wong, C.-H. J. Chem. Rev. 1996, 96, 443.
84. This process is a modification of Janda's recursive deconvolution of combinatorial libraries. Erb, E.; Janda, K. D.; Brenner, S. Proc. Natl. Acad. Sci. U.S.A. 1994, 91, 11422.
85. For other strategies for preparing and deconvoluting compounds from pools, see: (a) Sepetov, N. F.; Krchnak, V.; Stankova, M., Wade, S.; Lam, K. S.; Leble, M. Proc. Natl. Acad. Sci. U.S.A. 1995, 92, 5426. (b) Smith, P. W.; Lai, J. Y. Q.; Whittington, A. R.; Cox, B.; Houston, J. G. BioMed. Chem. Lett. 1994, 4, 2821. (c) Pirrung, M. C.; Chen, J. J. Am. Chem. Soc. 1995, 117, 1240. (d) Carell, T.; Wintner, E. A.; Rebek, J. Angew. Chem., Int. Ed. Engl. 1994, 33, 2061.
86. For other strategies for preparing and deconvoluting compounds from pools, see: (a) Sepetov, N. F.; Krchnak, V.; Stankova, M., Wade, S.; Lam, K. S.; Leble, M. Proc. Natl. Acad. Sci. U.S.A. 1995, 92, 5426. (b) Smith, P. W.; Lai, J. Y. Q.; Whittington, A. R.; Cox, B.; Houston, J. G. BioMed. Chem. Lett. 1994, 4, 2821. (c) Pirrung, M. C.; Chen, J. J. Am. Chem. Soc. 1995, 117, 1240. (d) Carell, T.; Wintner, E. A.; Rebek, J. Angew. Chem., Int. Ed. Engl. 1994, 33, 2061.
87. For other strategies for preparing and deconvoluting compounds from pools, see: (a) Sepetov, N. F.; Krchnak, V.; Stankova, M., Wade, S.; Lam, K. S.; Leble, M. Proc. Natl. Acad. Sci. U.S.A. 1995, 92, 5426. (b) Smith, P. W.; Lai, J. Y. Q.; Whittington, A. R.; Cox, B.; Houston, J. G. BioMed. Chem. Lett. 1994, 4, 2821. (c) Pirrung, M. C.; Chen, J. J. Am. Chem. Soc. 1995, 117, 1240. (d) Carell, T.; Wintner, E. A.; Rebek, J. Angew. Chem., Int. Ed. Engl. 1994, 33, 2061.
88. For other strategies for preparing and deconvoluting compounds from pools, see: (a) Sepetov, N. F.; Krchnak, V.; Stankova, M., Wade, S.; Lam, K. S.; Leble, M. Proc. Natl. Acad. Sci. U.S.A. 1995, 92, 5426. (b) Smith, P. W.; Lai, J. Y. Q.; Whittington, A. R.; Cox, B.; Houston, J. G. BioMed. Chem. Lett. 1994, 4, 2821. (c) Pirrung, M. C.; Chen, J. J. Am. Chem. Soc. 1995, 117, 1240. (d) Carell, T.; Wintner, E. A.; Rebek, J. Angew. Chem., Int. Ed. Engl. 1994, 33, 2061.
89. Sinha, S. C.; Sinha, A.; Yazbak, A.; Keinan, E. J. Org. Chem. 1996, 61, 7640.
90. (a) Postema, M. H. D. Tetrahedron 1992, 48, 8545-8599.
91. (b) Wei, A.; Haudrechy, A.; Audin, C.; Jun, H.-S.; Haudrechy-Bretel, N.; Kishi, Y. J. Org. Chem. 1995, 60, 2160.
92. (a) Nagy, J. O.; Wang, P.; Gilbert, J. H.; Schaefer, M. E.; Hill, T. G.; Callstrom, M. R.; Bednarski, M. D. J. Med. Chem. 1992, 35, 4501.
93. (b) Bertozzi, C. R.; Cook, D. G.; Kobertz, W. R.; Gonzalez-Scarano, F.; Bednarski, M. D. J. Am. Chem. Soc. 1992, 114, 10639.
94. (c) Bertozzi, C. R.; Bednarski, M. D. J. Am. Chem. Soc. 1992, 114, 5543.
95. (d) Mortell, K. H.; Weatherman, R. V.; Kiessling, L. L. J. Am. Chem. Soc. 1996, 118, 2297.
96. For exceptions, see: (e) Espinosa, J.-F.; Canada, F. J.; Asensio, J. L.; Dietrich, H.; Martin-Lomas, M.; Schmidt, R. R.; Jimenez-Barbero, J. Angew. Chem., Int. Ed. Engl. 1996, 35, 303. (f) O'Leary, D. J.; Kishi, Y. J. Org. Chem. 1994, 59, 6629.
97. For exceptions, see: (e) Espinosa, J.-F.; Canada, F. J.; Asensio, J. L.; Dietrich, H.; Martin-Lomas, M.; Schmidt, R. R.; Jimenez-Barbero, J. Angew. Chem., Int. Ed. Engl. 1996, 35, 303. (f) O'Leary, D. J.; Kishi, Y. J. Org. Chem. 1994, 59, 6629.
98. (a) Takai, K.; Kimura, K.; Kuroda, T.; Hiyama, T.; Nozaki, H. Tetrahedron Lett. 1983, 24, 5281.
99. (b) Cintas P. Synthesis 1992, 248.
100. (c) Hashmi, A. S. K. J. Prakt. Chem. 1996, 338, 491.
101. (a) Dyer, U. C.; Kishi, Y. J. Org. Chem. 1988, 53, 3383-3384.
102. (b) Kishi Y. Pure Appl. Chem. 1992, 64, 343-350.
103. Hosomi, A.; Sakata, Y.; Sakurai, H. Tetrahedron Lett. 1984, 25, 2383.
104. (a) Evans, D. A.; Fu, G. C.; Hoveyda, A. H. J. Am. Chem. Soc. 1988, 110, 6917.
105. (b) Evans, D. A.; Fu, G. C. J. Org. Chem. 1990, 55, 2280.
106. (c) Burgess, K.; Donk, W. A. van der; Westcott, S. A.; Marder, T. B.; Baker, R. T.; Calabrese, J. C. J. Am. Chem. Soc. 1992, 114, 9350.
107. (d) Burgess, K.; Ohhneyer, M. J. Chem. Rev. 1991, 91, 1179.
108. Since these alcohols were isolated as single diastereomers, presumably in 95% or greater de, we were inclined to assign their stereochemistry on the basis of examples at this preliminary stage. The assignment of these centers was later confirmed through proton NMR experiments performed on cyclic intermediates.
109. Evans, D. A.; Ratz, A. M.; Huff, B. E.; Sheppard, G. S. J. Am. Chem. Soc. 1995, 117, 3448-3467.
110. (a) Dess, D. B.; Martin, J. C. J Org. Chem. 1983, 48, 4156.
111. (b) Ireland, R. E.; Liu, L. J Org. Chem. 1993, 58, 2899.
112. (c) For preparation, follow Meyer, S. D.; Schreiber, S. L. J Org. Chem. 1994, 59, 7549.
113. (a) Brown, H. C.; Jadhau, P. K. J. Am. Chem. Soc. 1983, 105, 2092.
114. (b) Brown, H. C.; Jadhau, P. K.; Bhat, K. S. J. Am. Chem. Soc. 1988, 110, 1535.
115. (c) Brown, H. C.; Ramachandran, P. V. J. Organomet. Chem. 1995, 500, 1.
116. This assignment was further confirmed by NMR analysis of the tetrabenzylated 15.
117. Scarlato, G. R.; DeMattei, J. A.; Chong, L. S.; Ogawa, A. K.; Lin, M. R.; Armsrtong, R. W. J. Org. Chem. 1996, 61, 6139.
118. Yang, D.; Wong, M.-K.; Yip, Y.-C. J. Org. Chem. 1995, 60, 3887.
119. Compounds 8 and 9 could be separated via chromatography following an acetylation step.
120. Two fractions were obtained, one with 10% contamination by the other diastereomer and the other with a 15% contamination of the previous diastereomer.
121. Or 2,4-dideoxy-L-gulose for 15 and 2,4-dideoxy-D-taIose for 14.
122. Or 2,4-dideoxy-D-glucose for 8 and 2,4-dideoxy-L-idose for 7.
123. The tetrabenzylated precursors to 7 and 8 were individually analyzed via 2D COSY, 2D ROESY, and 2D HMQC to establish proton connectivity and then selectively decoupled to determine J values of individual resonances. This analysis resulted in the stereochemical assignment of these compounds. It was also at this point that the stereochemical outcomes of hydroboration and Felkin-Ahn addition for this series were confirmed. The stereochemistry of C-1 carbon (of the center sugar) in the precursor to 8 was known from X-ray crystallography and its proton was coupled to the C-2 proton with a large J value of 9.8 Hz, indicative of a trans-trans diaxial relationship. The C-3 proton was likewise coupled to C-2 with a 10.4 Hz coupling in addition to couplings with the C-4 axial proton (10.4 Hz) and to the C-4 equatorial proton (4.2 Hz). The C-4 equatorial proton, in addition to a geminal coupling to the C-4 axial proton (12.0 Hz), is weakly coupled to C-5, a pattern similar to the C-4 proton of galactose found in a previously synthesized C-1, C-2 branched C-trisaccharide (see ref 26a). The benzylated precursor to 7 was analyzed in a similar manner but was thought not to exist as a chair due to the combination of the unfavorable A 1,2 strain in the C-1 and C-2 branch points of the center sugar and the 1,3-diaxial interactions caused by C-6. This resulted in a more complicated spectrum with many small couplings between the ring protons, causing broader lines.
124. Kolb, H. C.; VanNieuwenhze, M. S.; Sharpless, K. B. Chem. Rev. 1994, 94, 2483.
125. Wang, Y.; Babirad, S. A.; Kishi, Y. J. Org. Chem. 1992, 57, 468-481.
126. (a) Bernotas, R. C.; Ganem, B. Tetrahedron Lett. 1985, 26, 1123.
127. (b) Pougny, J.-R.; Nassr, M. A. M.; Sinay, P. J. Chem. Soc., Chem. Commun. 1981, 375.
128. Benhamou, M. C.; Etemad-Moghadam, G.; Speziale, V.; Lattes, A. Synth. Commun. 1979, 891.
129. For compound 41 the two methyl resonances were irradiated to identify the neighboring C-5 protons. The C-5′ proton of the central hexose was distinguished from the C-5″ proton of the of the fucose by selectively spin-saturating these resonances and looking for an effect in the upfield methylene region. Irradiation of the C-6 methyl protons of the central hexose collapsed the C-5′ resonance to a doublet of doublets having identical J values of 4.2 Hz. This pattern is indicative of an equatorial proton in a six-membered ring chair with two small coupling's to a α methylene.
130. Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis; 2nd ed.; Wiley-Interscience: New York, 1991.
131. 1H decouplings. The C-4′ stereocenter was assumed to have an axial proton derived from the (Z)-boronenolate in the Brown allylboration. This was confirmed via a 9.1 Hz coupling to the C-3′ proton, also axial. Irradiation of the C-5′ proton gave an NOE with the C-6′ and C-4′ protons however, irradiation of either the C-4′ or C-6′ protons could not indicate an NOE between each other. This established a C-4′ proton to C-6′ diaxial relationship.
132. The author has deposited atomic coordinates for structure 23 with the Cambridge Crystallographic Data Centre. The coordinates can be obtained, on request, from the Director, Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge, CB2 1EZ, UK.