Citation: Xu Weichang, Liu Wei, Li Xiang, Xu Peng, Yu Biao. Synthesis of Oligosaccharides Relevant to the Substrates of Heparanase via Dehydrative Glycosylation[J]. Acta Chimica Sinica, ;2020, 78(8): 767-777. doi: 10.6023/A20060201 shu

Synthesis of Oligosaccharides Relevant to the Substrates of Heparanase via Dehydrative Glycosylation

Xu Weichang ^a ,
Liu Wei ^b ,
Li Xiang ^c ,
Xu Peng ^a,, ,
Yu Biao ^a,b,,

a.
State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China
b.
School of Physical Science and Technology, ShanghaiTech University, Shanghai 201210
c.
Department of Chemistry, The University of Hong Kong, Hong Kong 999077

Corresponding author: Xu Peng, peterxu@sioc.ac.cn Yu Biao, byu@sioc.ac.cn
Received Date: 1 June 2020
Available Online: 28 June 2020
Fund Project: Youth Innovation Promotion Association of CAS 2020258Financial support from National Natural Science Foundation of China (Nos. 21621002 & 21602240), Key Research Program of Frontier Sciences of CAS (No. ZDBS-LY-SLH030), Strategic Priority Research Program of CAS (No. XDB20020000), and Youth Innovation Promotion Association of CAS (No. 2020258) are acknowledgedNational Natural Science Foundation of China 21602240National Natural Science Foundation of China 21621002Strategic Priority Research Program of CAS XDB20020000Key Research Program of Frontier Sciences of CAS ZDBS-LY-SLH030

Figures(8)

Heparanase, an endo-b-D-glucuronidase responsible for specific cleavage of heparin and heparan sulfates, is relevant to a number of biological processes, such as inflammation, tumor angiogenesis and metastasis. Heparin and heparan sulfate(HS), ubiquitously distributed on the cell surface and in the extracellular matrix, play significant roles in a diverse set of biological processes, including cell growth, virus infection, and tumor metastasis. The substrate specificity of the purified recombinant human heparinase has been investigated, and an optimal tetrasaccharide substrate of heparinase was found to be DHexUA(2S)-GlcN(NS, 6S)-GlcUA-GlcN(NS, 6S). Here we report an efficient alternative to the chemical synthesis of oligosaccharides relevant to the substrates of heparanase, including the stereoselective construction of a-GlcN-(1→4)-GlcA glycoside bonds and the effective post-assembly manipulations on the fully elaborated oligosaccharides. The dehydrative glycosylation protocol, capitalizing on direct activation of C1-hemiacetals as glycosyl donors, was employed to construct the challenging a-GlcN-(1→4)-GlcA linkages, using diphenyl sulfoxide(Ph₂SO)/triflic anhydride(Tf₂O) as promoters, 2, 4, 6-tri-tert- butylpyrimidine(TTBP) as base, toluene as a solvent, and －60 ℃ to room temperature as the working temperature. Under these optimized conditions, mono- and disaccharide donors(9 and 10) and disaccharide acceptors(11 and 12) were condensed to provide the coupled tri- and tetrasaccharides 5~8 in good yields and satisfactory stereoselectivity(>65% yield and a/b>5.4/1.0). The fully elaborated oligosaccharides 5~8 have then been successfully transformed into the target heparin oligosaccharides 1~4 via an effective sequence of manipulation of the protecting groups(>52% yield for 5 steps). The post-assembly manipulations include saponification under Zemplén conditions(for removal of benzyl ester and benzoyl group), O-sulfonation with sulfur trioxide pyridine complex(for hydroxyl groups), reduction and N-sulfonation(for azido group), and high pressure hydrogenation(for removal of benzyl groups). The availability of these heparin oligosaccharides would facilitate in-depth elucidation of the substrate selectivity of heparanase and the development of an effective assay for measuring the heparanase activities.
- heparanase,
- heparin oligosaccharide,
- a-(1→4) glycosidic bond,
- dehydrative glycosylation,
- chemical synthesis
1. [1]
  Molean, J. Am. J. Physiol. 1916, 41, 250. doi: 10.1152/ajplegacy.1916.41.2.250
2. [2]
  Capila, R. J. Linhardt, D. Angew. Chem. Int. Ed. 2002, 41, 390. doi: 10.1002/1521-3773(20020201)41:3<390::AID-ANIE390>3.0.CO;2-B
3. [3]
  (a) Petitou, M.; van Boeckel, C. A. A. Angew. Chem. Int. Ed. Engl. 1993, 32, 1671; (b) Petitou, M.; van Boeckel, C. A. A. Angew. Chem. Int. Ed. 2004, 43, 3118.
4. [4]
5. [5]
  Poletti, L.; Lay, L. Eur. J. Org. Chem. 2003, 2999; (b) Karst, N. A.; Linhardt, R. J. Curr. Med. Chem. 2003, 10, 1993.
6. [6]
  Vlodavsky, I.; Goldshmidt, O.; Zcharia, E.; Metzger, S.; Chajek-Shaul, T.; Atzmon, R.; Guatta-Rangini, Z.; Friedmann, Y. Biochimie 2001, 83, 831. doi: 10.1016/S0300-9084(01)01318-9
7. [7]
  Elkin, M.; Ilan, N.; Ishai-Michaeli, R. FASEB 2001, 15, 1661. doi: 10.1096/fj.00-0895fje
8. [8]
  Bartleet, M. R.; Underwood, P. A.; Parish, C. R. Immunol. Cell Biol. 1995, 73, 113. doi: 10.1038/icb.1995.19
9. [9]
  Bingley, J. A.; Hayward, I. P.; Campbell, J. H. J. Vasc. Surg. 1998, 28, 308. doi: 10.1016/S0741-5214(98)70167-3
10. [10]
  Okada, Y.; Yamada, S.; Toyoshima, M.; Dong, J.; Nakajima, M.; Sugahara, K. J. Biol. Chem. 2002, 277, 42488. doi: 10.1074/jbc.M206510200
11. [11]
  For reviews, see: (a) Gin, D. J. Carbohydr. Chem. 2002, 21, 645; (b) O'Neill, S.; Rodriguez, J.; Walczak, M. A. Chem. Asian J. 2018, 13, 2978; (c) Ryan, D. A.; Gin, D. Y. Glycoside Synthesis from 1-Oxygen Substituted Glycosyl Donors. In Handbook of Chemical Glycosylation, Ed.: Demchenko, A. V., Wiley-Ver & Co. KGaA, Weinheim, 2008, pp. 95–143.
12. [12]
  (a) Chen, J.; Zhou, Y.; Chen, C.; Xu, W.; Yu, B. Carbohydr. Res. 2008, 343, 2853; (b) Xu, P.; Xu, W.; Dai, Y.; Yang, Y.; Yu, B. Org. Chem. Front. 2014, 1, 405.
13. [13]
  Jiang, L.; Chan, T. Tetrahedron Lett. 1998, 39, 355. doi: 10.1016/S0040-4039(97)10599-8
14. [14]
  Epp, J. B.; Widlanski, T. S. J. Org. Chem., 1999, 64, 293. doi: 10.1021/jo981316g
15. [15]
  (a) Yin, X.; Yan, J.; Ji, S.; Wang, F.; Cao, H. Chin. J. Org. Chem. 2012, 32, 1388; (b) Li, J.; Dai, Y.; Li, W.; Laval, S.; Xu, P.; Yu, B. Asian J. Org. Chem. 2015, 4, 756; (c) Mende, M.; Bednarek, C.; Wawryszyn, M.; Sauter, P.; Biskup, M. B.; Schepers, U.; Brase, S. Chem. Rev. 2016, 116, 8193
16. [16]
  (a) Nishida, Y.; Shingu, Y.; Dohi, H.; Kobayashi, K. Org. Lett. 2003, 5, 2377; (b) Kim, K. S.; Fulse, D. B.; Baek, J. Y.; Lee, B.-Y.; Jeon, H. B. J. Am. Chem. Soc. 2008, 130, 8537; (c) Mossotti, M.; Panza, L. J. Org. Chem. 2011, 76, 9122; (d) Nogueira, J. M.; Nguyen, S. H.; Bennett, C. S. Org. Lett. 2011, 13, 2814; (e) Nogueira, J. M.; Bylsma, M.; Bright, D. K.; Bennett, C. S. Angew. Chem. Int. Ed. 2016, 55, 10088; (f) Zhou, M.-H.; Wilbur, D. J.; Kwan, E. E.; Bennett, C. S. J. Am. Chem. Soc. 2019, 141, 16743; (g) Dyapa, R.; Dockery, L. T.; Walczak, M. A. Org. Biomol. Chem. 2017, 15, 51; (h) Ghosh, T.; Mukherji, A.; Srivastava, H. K.; Kancharla, P. K. Org. Biomol. Chem. 2018, 16, 2870; (i) Manhas, S.; Taylor, M. S. Carbohydr. Res. 2018, 470, 42; (j) Cai, L.; Zeng, J.; Li, T.; Xiao, Y.; Ma, X.; Xiao, X.; Zhang, Q.; Meng, L.; Wan, Q. Chin. J. Chem. 2020, 38, 43.
17. [17]
  (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.
18. [18]
  (a) Codée, J. D. C.; van den Bos, L. J.; Litjens, R. E. J. N.; Overkleeft, H. S.; van Boom J. H.; van der Marel, G. A. Org. Lett. 2003, 5, 1947; (b) van den Bos, L. J.; Codée, J. D. C.; van Boom J. H.; Overkleeft, H. S.; van der Marel, G. A. Org. Biomol. Chem. 2003, 1, 4160; (c) van den Bos, L. J.; Codée, J. D. C.; van Boom, J. H.; van der Toorn, J. C.; Boltje, T. J.; van Boom J. H.; Overkleeft, H. S.; van der Marel, G. A. Org. Lett. 2004, 6, 2165; (d) Codée, J. D. C.; Stubba, B.; Schiattarella, M.; Overkleeft, H. S.; van Boeckel, C. A. A.; van Boom J. H.; van der Marel, G. A. J. Am. Chem. Soc. 2005, 127, 3767.
19. [19]
  Zhou, Y. Ph.D. Dissertation, Shanghai Institute of Organic Chemistry, CAS, Shanghai, 2005 (in Chinese).
20. [20]
  (a) Arungundram, S.; Al-Mafraji, K.; Asong, J.; Leach III, F. E.; Amster, J., Venot, A.; Turnbull, J. E.; and Boons, G. J. Am. Chem. Soc. 2009, 131, 17394; (b) Hu, Y.; Lin, S.; Huang, C.; Zulueta, M. M. L.; Liu J.; Chang, W.; Hung, S.-C. Nat. Chem. 2011, 3, 557; (c) Zulueta, M.; Lin, S.; Lin, Y.; Huang, C.; Wang, C.; Ku, C.; Shi, Z.; Wong, C.-H.; Hung, S.-C. J. Am. Chem. Soc. 2012, 134, 8988; (d) Wang, Z.; Xu, Y.; Yang B., Tiruchinapally, G.; Sun, B.; Liu, R.; Dulaney, S.; Liu, J.; Huang, X. Chem. Eur. J. 2010, 16, 8365; (e) Haller, M.; Boons, G-J. J. Chem. Soc., Perkin Trans.1. 2001, 814; (f) Lubineau, A.; Lortat-Jacob, H.; Gavard, O.; Sarrazin, S.; Bonnaffé, D. Chem. Eur. J. 2004, 10, 4265; (g) Lin, F.; Lian, G.; Zhou, Y. Carbohydr. Res. 2013, 371, 32; (h) Li, T.; Ye, H.; Cao, X.; Wang, J.; Liu, Y.; Zhou, L.; Liu, Q.; Wang, W.; Shen, J. Zhao, W.; Wang, P. ChemMedChem 2014, 9, 1071; (i) Xu, P.; Laval, S.; Guo, Z.; Yu, B. Org. Chem. Front. 2016, 3, 103; (j) Dai, X.; Liu, W.; Zhou, Q.; Cheng, C.; Yang, C.; Wang, S.; Zhang, M.; Tang, P.; Song, H.; Zhang, D.; Qin, Y. J. Org. Chem. 2016, 81, 162; (k) Ding, Y.; Vara Prasad C. V. N. S.; Bai, H.; Wang, B. Bioorg. Med. Chem. Lett. 2017, 27, 2424; (l) Jin, H.; Chen, Q.; Zhang, Y.; Hao, K. Zhang, G.; Zhao, W. Org. Chem. Front. 2019, 6, 3116.
21. [21]
  (a) Orgueira, H. A.; Bartolozzi, A.; Schell, P.; Litjens, R. E. J. N.; Palmacci, E. R.; Seeberger, P. H. Chem. Eur. J. 2003, 9, 140; (b) Noti, C.; de Paz, J. L.; Polito, L.; Seeberger, P. H. Chem. Eur. J. 2006, 12, 8664; (c) Zhang, L.; Xu, P.; Liu, B.; Yu, B. J. Org. Chem. 2020, DOI: 10.1021/acs.joc.0c01009.
22. [22]
  (a) Mungall, W. S.; Greene, G. L.; Heavner, G. A.; Letsinger, R. L. J. Org. Chem. 1975, 40, 1659; (b) Alper, P. B.; Hendrix, M.; Sears, P.; Wong, C. H. J. Am. Chem. Soc. 1998, 120, 1965.
23. [23]
  Bayley, H.; Standring, D. N.; Knowles, J. R. Tetrahedron Lett. 1978, 19, 3633.
24. [24]
  Corey, E. J.; Nicolaou, K. C.; Balanson, R. D.; Machida, Y. Synthesis 1975, 590.
25. [25]
  Lee, J.-C.; Lu, X.-A.; Kulkarni, S. S.; Wen, Y.-S.; Hung, S.-C. J. Am. Chem. Soc. 2003, 126, 476.
26. [26]
  (a) Benati, L.; Montevecchi, P. C.; Nanni, D.; Spagnolo, P.; Volta, M. Tetrahedron Lett. 1995, 36, 7313; (b) Goulaouic-Dubois, C.; Hesse, M. Tetrahedron Lett. 1995, 36, 7427.
27. [27]
  Brewer, M.; Rich, D. H. Org. Lett. 2001, 3, 945. doi: 10.1021/ol015612i
28. [28]
  Gregory, J.; Lohman, S.; Seeberger, P. H. J. Org. Chem. 2004, 69, 4081. doi: 10.1021/jo035732z
29. [29]
  Yang, B.; Yoshida, K.; Yin, Z.; Dai, H.; Kavunja, H.; El-Dakdouki, M. H.; Sungsuwan, S.; Dulaney, S. B.; Huang, X. Angew. Chem., Int. Ed. 2012, 51, 10185. doi: 10.1002/anie.201205601
30. [30]
31. [31]
  Dilhas, A.; Lucas, R.; Loureiro-Morais, L.; Hersant, Y.; Bonnaffé, D. J. Comb. Chem. 2008, 10, 166. doi: 10.1021/cc8000019
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