多糖化学合成研究进展

doi:10.6023/A19040128

摘要/Abstract

多糖是一类结构复杂的生物大分子，广泛分布于微生物、植物、动物等生物体中，参与众多重要的生命过程.然而，多糖研究一直受限于难以获得足量结构均一的多糖物质，这使得多糖的结构和功能研究及其相关的应用研究进展缓慢.近几十年来，随着糖合成技术的进步，糖的化学合成效率不断提高，人们开始关注复杂多糖的化学合成，并取得了一些进展.本文主要对多糖化学合成所涉及的糖基化方法、糖组装策略和代表性的合成工作进行综述，并对研究前景进行展望.

关键词: 多糖, 化学合成, 糖基化方法, 合成策略

Polysaccharides are a class of bio-macromolecules with highly complex structures that are widely found in living organisms such as microorganisms, plants and animals. Polysaccharides serve not only as structural components and energy sources of cells, but also as important signaling molecules which are involved in many key biological processes. Studies on polysaccharide-mediated biological processes require access to structurally defined molecules, which approach the size and complexity of those found in nature, but naturally-occurring polysaccharides usually exist in microheterogeneous forms, making it difficult or even impossible to isolate pure polysaccharides from natural sources in most cases. Chemical synthesis represents a reliable solution to this problem, which can provide polysaccharide samples with defined chemical structures for functional studies and even a library of analogs of natural glycans for structure-activity relationship investigations. But unlike oligonucleotides and peptides, which can already be obtained by automated synthesizers in a very short of time, the chemical synthesis of glycans remains a great challenge for synthetic chemists. The major challenge for glycan synthesis lies in the need to handle both stereo-and regio-chemistry in the construction of each glycosyl linkage, and the extensive protecting-group manipulations as well as much intermediate separation make it a tedious and time-consuming process. Over the past decades, carbohydrate chemists have developed many glycosylation reactions. A series of strategies for glycan assembly have been also established. The advances in both synthetic methods and strategies have significantly increased the synthetic efficiency of carbohydrate molecules, and many great accomplishments in the field of polysaccharide synthesis have been witnessed in recent decades. Some representative methods and strategies, and their successful applications in the chemical synthesis of complex polysaccharides are summarized in this review.

Key words: polysaccharide, chemical synthesis, glycosylation method, synthetic strategy

引用此文

吴勇, 叶新山. 多糖化学合成研究进展[J]. 化学学报, 2019, 77(7): 581-597.

Wu Yong, Ye Xin-Shan. Recent Advances in Chemical Synthesis of Polysaccharides[J]. Acta Chim. Sinica, 2019, 77(7): 581-597.

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参考文献

[1] Varki, A. Glycobiology 1993, 3, 97.
[2] Krasnova, L.; Wong, C.-H. Annu. Rev. Biochem. 2016, 85, 599.
[3] Boltje, T. J.; Buskas, T.; Boons, G.-J. Nat. Chem. 2009, 1, 611.
[4] Seeberger, P. H.; Werz, D. B. Nature 2007, 446, 1046.
[5] (a) Gao, Y.; Cao, Z.; Han, Z.; Zhang, Q.; Hu, J.; Guo, R.; He, X.; Ding, F.; You, Q.; Zhang, Y. Chin. J. Org. Chem. 2019, 39, 390. (高阳光, 曹周, 韩忠享, 张强, 胡杰, 郭锐, 贺贤然, 丁菲, 尤庆亮, 张勇民, 有机化学, 2019, 39, 390);
(b) Guo, Q.; Wang, X.; Huang, C.; Zhang, P.; Li, Y.; Chen, B. Chin. J. Org. Chem. 2018, 38, 940. (邱果, 王新承, 黄崇品, 张璞, 李英霞, 陈标华, 有机化学, 2018, 38, 940);
(c) Yuan, W.; Huang, Y.; Wu, C.; Liu, X.; Xia, Y.; Wang, H. Chin. J. Chem. 2017, 35, 1739;
(d) Guo, B.; Ye, L.; Tang, G.; Zhang, L.; Yue, B.; Tsang, S. C. E.; He, H. Chin. J. Chem. 2017, 35, 1529;
(e) Mao, R.; Sun, L.; Wang, Y.-S.; Zhou, M.-M.; Xiong, D.-C.; Li, Q.; Ye, X.-S. Chin. Chem. Lett. 2018, 29, 61;
(f) Tang, S.; Xiong, D.-C.; Jiang, S.; Ye, X.-S. Org. Lett. 2016, 18, 568.
[6] Bertozzi, C. R.; Kiessling, L. L. Science 2001, 291, 2357.
[7] Gabius, H.-J. The Sugar Code:Fundamentals of Glycosciences, John Wiley & Sons, New Jersey, 2011.
[8] Tanaka, H.; Kawai, T.; Adachi, Y.; Hanashima, S.; Yamaguchi, Y.; Ohno, N.; Takahashi, T. Bioorg. Med. Chem. 2012, 20, 3898.
[9] Petitou, M.; Duchaussoy, P.; Driguez, P.-A.; Hérault, J.-P.; Lormeau, J.-C.; Herbert, J.-M. Bioorg. Med. Chem. Lett. 1999, 9, 1155.
[10] Wang, L.; Feng, S.; An, L.; Gu, G.; Guo, Z. J. Org. Chem. 2015, 80, 10060.
[11] (a) Zhu, X.; Schmidt, R. R. Angew. Chem. Int. Ed. 2009, 48, 1900;
(b) Hsu, C.-H.; Hung, S.-C.; Wu, C.-Y.; Wong, C.-H. Angew. Chem. Int. Ed. 2011, 50, 11872;
(c) Seeberger, P. H. Acc. Chem. Res. 2015, 48, 1450;
(d) Kulkarni, S. S.; Wang, C.-C.; Sabbavarapu, N. M.; Podilapu, A. R.; Liao, P.-H.; Hung, S.-C. Chem. Rev. 2018, 118, 8025.
[12] Michael, A. Am. Chem. J. 1879, 1, 305.
[13] Toshima, K.; Tatsuta, K. Chem. Rev. 1993, 93, 1503.
[14] (a) Garcia, B. A.; Poole, J. L.; Gin, D. Y. J. Am. Chem. Soc. 1997, 119, 7597;
(b) Garcia, B. A.; Gin, D. Y. J. Am. Chem. Soc. 2000, 122, 4269.
[15] (a) Schmidt, R. R.; Michel, J. Angew. Chem. Int. Ed. 1980, 19, 731;
(b) Schmidt, R. R. Angew. Chem. Int. Ed. 1986, 25, 212.
[16] (a) Codée, J. D. C.; Litjens, R. E. J. N.; van den Bos, L. J.; Overkleeft, H. S.; van der Marel, G. A. Chem. Soc. Rev. 2005, 34, 769;
(b) Lian, G.; Zhang, X.; Yu, B. Carbohydr. Res. 2015, 403, 13.
[17] Mootoo, D. R.; Konradsson, P.; Udodong, U.; Fraser-Reid, B. J. Am. Chem. Soc. 1988, 110, 5583.
[18] Danishefsky, S. J.; Bilodeau, M. T. Angew. Chem. Int. Ed. 1996, 35, 1380.
[19] Plante, O. J.; Palmacci, E. R.; Andrade, R. B.; Seeberger, P. H. J. Am. Chem. Soc.2001, 123, 9545.
[20] Yu, B. Acc. Chem. Res. 2018, 51, 507.
[21] Koenigs, W.; Knorr, E. Ber. Dtsch. Chem. Ges. 1901, 34, 957.
[22] Zemplén, G.; Gerecs, A. Ber. Dtsch. Chem. Ges. 1930, 63, 2720.
[23] Helferich, B.; Wedemeyer, K. F. Justus Liebigs Ann. Chem. 1949, 563, 139.
[24] Igarashi, K.; Irisawa, J.; Honma, T. Carbohydr. Res. 1975, 39, 213.
[25] Kronzer, F. J.; Schuerch, C. Carbohydr. Res. 1973, 27, 379.
[26] Wulff, G.; Röhle, G.; Krüger, W. Chem. Ber. 1972, 105, 1097.
[27] Yamada, H.; Hayashi, T. Carbohydr. Res. 2002, 337, 581.
[28] Bernstein, S.; Conrow, R. B. J. Org. Chem. 1971, 36, 863.
[29] Nishizawa, M.; Garcia, D. M.; Shin, T.; Yamada, H. Chem. Pharm. Bull. 1993, 41, 784.
[30] Mukaiyama, T.; Murai, Y.; Shoda, S. Chem. Lett. 1981, 10, 431.
[31] Mukaiyama, T.; Hashimoto, Y.; Shoda, S. Chem. Lett. 1983, 12, 935.
[32] Matsumoto, T.; Maeta, H.; Suzuki, K. Tetrahedron Lett. 1988, 29, 3567.
[33] Hashimoto, S.; Hayashi, M.; Noyori, R. Tetrahedron Lett. 1984, 25, 1379.
[34] Mukaiyama, T.; Jona, H.; Takeuchi, K. Chem. Lett. 2000, 29, 696.
[35] Zhu, X.; Schmidt, R. R. Angew. Chem., Int. Ed. 2009, 48, 1900.
[36] El-Badry, M. H.; Gervay-Hague, J. Tetrahedron Lett. 2005, 46, 6727.
[37] (a) Lam, S. N.; Gervay-Hague, J. Carbohydr. Res. 2002, 337, 1953;
(b) Lam, S. N.; Gervay-Hague, J. Org. Lett. 2002, 4, 2039;
(c) Lam, S. N.; Gervay-Hague, J. J. Org. Chem. 2005, 70, 2387.
[38] Sun, L.; Wu, X.; Xiong, D.-C.; Ye, X.-S. Angew. Chem. Int. Ed. 2016, 55, 8041.
[39] Park, Y.; Harper, K. C.; Kuhl, N.; Kwan, E. E.; Liu, R. Y.; Jacobsen, E. N. Science 2017, 355, 162.
[40] Schmidt, R. R.; Toepfer, A. Tetrahedron Lett. 1991, 32, 3353.
[41] Yu, B.; Tao, H. Tetrahedron Lett. 2001, 42, 2405.
[42] Ferrier, R. J.; Hay, R. W.; Vethaviyasar, N. Carbohydr. Res. 1973, 27, 55.
[43] Veeneman, G. H.; Van Leeuwen, S. H.; Van Boom, J. H. Tetrahedron Lett. 1990, 31, 1331.
[44] Konradsson, P.; Udodong, U. E.; Fraser-Reid, B. Tetrahedron Lett. 1990, 31, 4313.
[45] Andersson, F.; Fúgedi, P.; Garegg, P. J.; Nashed, M. Tetrahedron Lett. 1986, 27, 3919.
[46] Martichonok, V.; Whitesides, G. M. J. Org. Chem. 1996, 61, 1702.
[47] Crich, D.; Smith, M. J. Am. Chem. Soc. 2001, 123, 9015.
[48] Codée, J. D. C.; Litjens, R. E. J. N.; den Heeten, R.; Overkleeft, H. S.; van Boom, J. H.; van der Marel, G. A. Org. Lett. 2003, 5, 1519.
[49] Wang, C.; Wang, H.; Huang, X.; Zhang, L.-H.; Ye, X.-S. Synlett 2006, 2846.
[50] Marra, A.; Mallet, J. M.; Amatore, C.; Sinaÿ, P. Synlett 1990, 572.
[51] (a) Mitsudo, K.; Kawaguchi, T.; Miyahara, S.; Matsuda, W.; Kuroboshi, M.; Tanaka, H. Org. Lett. 2005, 7, 4649;
(b) Nokami, T.; Shibuya, A.; Tsuyama, H.; Suga, S.; Bowers, A. A.; Crich, D.; Yoshida, J. I. J. Am. Chem. Soc. 2007, 129, 10922.
[52] (a) Nakanishi, M.; Takahashi, D.; Toshima, K. Org. Biomol. Chem. 2013, 11, 5079;
(b) Wever, W. J.; Cinelli, M. A.; Bowers, A. A. Org. Lett. 2012, 15, 30;
(c) Mao, R.-Z.; Guo, F.; Xiong, D.-C.; Li, Q.; Duan, J.; Ye, X.-S. Org. Lett. 2015, 17, 5606;
(d) Mao, R.-Z.; Xiong, D.-C.; Guo, F.; Li, Q.; Duan, J.; Ye, X.-S. Org. Chem. Front. 2016, 3, 737;
(e) Spell, M. L.; Deveaux, K.; Bresnahan, C. G.; Bernard, B. L.; Sheffield, W.; Kumar, R.; Ragains, J. R. Angew. Chem. Int. Ed. 2016, 55, 6515;
(f) Yu, Y.; Xiong, D.-C.; Mao, R.-Z.; Ye, X.-S. J. Org. Chem. 2016, 81, 7134.
(g) Wang, H.; Wu, P.; Zhao, X.; Zeng, J.; Wan, Q. Acta Chim. Sinica 2019, 77, 231. (王浩, 吴品儒, 赵祥, 曾静, 万谦, 化学学报, 2019, 77, 231.);
(h) Ye, H.; Xiao, C.; Lu, L. Chin. J. Org. Chem. 2018, 38, 1897. (叶辉, 肖聪, 陆良秋, 有机化学, 2018, 38, 1897.)
[53] Goswami, M.; Ellern, A.; Pohl, N. L. B. Angew. Chem. Int. Ed. 2013, 52, 8441.
[54] Yamada, H.; Harada, T.; Miyazaki, H.; Takahashi, T. Tetrahedron Lett. 1994, 35, 3979.
[55] Zhang, Z.; Ollmann, I. R.; Ye, X.-S.; Wischnat, R.; Baasov, T.; Wong, C.-H. J. Am. Chem. Soc. 1999, 121, 734.
[56] Huang, X.; Huang, L.; Wang, H.; Ye, X.-S. Angew. Chem Int. Ed. 2004, 43, 5221.
[57] Plante, O. J.; Palmacci, E. R.; Seeberger, P. H. Science 2001, 291, 1523.
[58] Tanaka, H.; Adachi, M.; Tsukamoto, H.; Ikeda, T.; Yamada, H.; Takahashi, T. Org. Lett. 2002, 4, 4213.
[59] Yu, B.; Yu, H.; Hui, Y.; Han, X. Tetrahedron Lett. 1999, 40, 8591.
[60] Wang, P.; Lee, H.; Fukuda, M.; Seeberger, P. H. Chem. Commun. 2007, 1963.
[61] Vohra, Y.; Buskas, T.; Boons, G.-J. J. Org. Chem. 2009, 74, 6064.
[62] (a) Hsu, C.-H.; Chu, K. C.; Lin, Y. S.; Han, J. L.; Peng, Y. S.; Ren, C. T.; Wong, C.-H. Chem. Eur. J. 2010, 16, 1754;
(b) Tanaka, H.; Tateno, Y.; Nishiura, Y.; Takahashi, T. Org. Lett. 2008, 10, 5597;
(c) Tanaka, H.; Adachi, M.; Takahashi, T. Chem. Eur. J. 2005, 11, 849.
[63] (a) Dinkelaar, J.; Gold, H.; Overkleeft, H. S.; Codée, J. D.; van der Marel, G. A. J. Org. Chem. 2009, 74, 4208;
(b) Hu, Y. P.; Lin, S. Y.; Huang, C. Y.; Zulueta, M. M. L.; Liu, J. Y.; Chang, W.; Hung, S.-C. Nat. Chem. 2011, 3, 557.
[64] Sarkar, S.; Dutta, S.; Das, G.; Sen, A. K. Tetrahedron 2011, 67, 4118.
[65] Burkhart, F.; Zhang, Z.; Wacowich-Sgarbi, S.; Wong, C.-H. Angew. Chem. Int. Ed. 2001, 40, 1274.
[66] Tsai, B. L.; Han, J. L.; Ren, C. T.; Wu, C.-Y.; Wong, C.-H. Tetrahedron Lett. 2011, 52, 2132.
[67] Mong, K. K. T.; Wong, C.-H. Angew. Chem. Int. Ed. 2002, 41, 4087.
[68] Lee, J. C.; Wu, C.-Y.; Apon, J. V.; Siuzdak, G.; Wong, C.-H. Angew. Chem. Int. Ed. 2006, 45, 2753.
[69] Mong, T. K. K.; Lee, H. K.; Durón, S. G.; Wong, C.-H. PNAS 2003, 100, 797.
[70] Polat, T.; Wong, C.-H. J. Am. Chem. Soc. 2007, 129, 12795.
[71] Hsu, Y.; Lu, X. A.; Zulueta, M. M. L.; Tsai, C. M.; Lin, K. I.; Hung, S.-C.; Wong, C.-H. J. Am. Chem. Soc. 2012, 134, 4549.
[72] Wang, Z.; Zhou, L.; El-Boubbou, K.; Ye, X.-S.; Huang, X. J. Org. Chem. 2007, 72, 6409.
[73] Li, Q.; Guo, Z. Org. Lett. 2017, 19, 6558.
[74] Huang, L.; Huang, X. Chem. Eur. J. 2007, 13, 529.
[75] Miermont, A.; Zeng, Y.; Jing, Y.; Ye, X.-S.; Huang, X. J. Org. Chem. 2007, 72, 8958.
[76] Wang, Z.; Xu, Y.; Yang, B.; Tiruchinapally, G.; Sun, B.; Liu, R.; Huang, X. Chem. Eur. J. 2010, 16, 8365.
[77] Sun, B.; Srinivasan, B.; Huang, X. Chem. Eur. J. 2008, 14, 7072.
[78] Wang, Y.-S.; Wu, Y.; Xiong, D.-C.; Ye, X.-S. Chin. J. Chem. 2019, 37, 42.
[79] (a) Gao, J.; Guo, Z. J. Org. Chem. 2013, 78, 12717;
(b) Gao, J.; Liao, G.; Wang, L.; Guo, Z. Org. Lett. 2014, 16, 988;
(c) Gao, J.; Guo, Z. Org. Lett. 2016, 18, 5552.
(d) Wang, D.; Xiong, D.-C.; Ye, X.-S. Chin. Chem. Lett. 2018, 29, 1340;
(e) Wu, Y.; Xiong, D.-C.; Chen, S.-C.; Wang, Y.-S.; Ye, X.-S. Nat. Commun. 2017, 8, 14851.
[80] Werz, D. B.; Castagner, B.; Seeberger, P. H. J. Am. Chem. Soc. 2007, 129, 2770.
[81] Routenberg, L. K.; Seeberger, P. H. Angew. Chem. Int. Ed. 2004, 43, 602.
[82] Ratner, D. M.; Swanson, E. R.; Seeberger, P. H. Org. Lett. 2003, 5, 4717.
[83] Codée, J. D. C.; Kröck, L.; Castagner, B.; Seeberger, P. H. Chem. Eur. J. 2008, 14, 3987.
[84] (a) Walvoort, M. T. C.; Volbeda, A. G.; Reintjens, N. R. M.; van den Elst, H.; Plante, O. J.; Overkleeft, H. S.; Codée, J. D. Org. Lett. 2012, 14, 3776;
(b) Hahm, H. S.; Broecker, F.; Kawasaki, F.; Mietzsch, M.; Heilbronn, R.; Fukuda, M.; Seeberger, P. H. Chem 2017, 2, 114.
[85] Hewitt, M. C.; Snyder, D. A.; Seeberger, P. H. J. Am. Chem. Soc. 2002, 124, 13434.
[86] Matsuzaki, Y.; Ito, Y.; Nakahara, Y.; Ogawa, T. Tetrahedron Lett. 1993, 34, 1061.
[87] Hansen, S. U.; Miller, G. J.; Cliff, M. J.; Jayson, G. C.; Gardiner, J. M. Chem. Sci. 2015, 6, 6158.
[88] Li, A.; Kong, F. Bioorg. Med. Chem. 2005, 13, 839.
[89] Pozsgay, V. Angew. Chem. Int. Ed. 1998, 37, 138.
[90] Pozsgay, V.; Chu, C.; Pannell, L.; Wolfe, J.; Robbins, J. B.; Schneerson, R. PNAS 1999, 96, 5194.
[91] Pozsgay, V. Tetrahedron:Asymmetry 2000, 11, 151.
[92] Joe, M.; Bai, Y.; Nacario, R. C.; Lowary, T. L. J. Am. Chem. Soc. 2007, 129, 9885.
[93] Ishiwata, A.; Ito, Y. J. Am. Chem. Soc. 2011, 133, 2275.
[94] Thadke, S. A.; Mishra, B.; Islam, M.; Pasari, S.; Manmode, S.; Rao, B. V.; Hotha, S. Nat. Commun. 2017, 8, 14019.
[95] Pasari, S.; Manmode, S.; Walke, G.; Hotha, S. Chem. Eur. J. 2018, 24, 1128.
[96] Mishra, B.; Neralkar, M.; Hotha, S. Angew. Chem. Int. Ed. 2016, 55, 7786.
[97] Fraser-Reid, B.; Lu, J.; Jayaprakash, K. N.; Lopez, J. C. Tetrahedron:Asymmetry 2006, 17, 2449.
[98] Islam, M.; Shinde, G. P.; Hotha, S. Chem. Sci. 2017, 8, 2033.
[99] Calin, O.; Eller, S.; Seeberger, P. H. Angew. Chem. Int. Ed. 2013, 52, 5862.
[100] Naresh, K.; Schumacher, F.; Hahm, H. S.; Seeberger, P. H. Chem. Commun. 2017, 53, 9085.
[101] Yu, Y.; Kononov, A.; Delbianco, M.; Seeberger, P. H. Chem. Eur. J. 2018, 24, 6075.