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
1. [1]
  Xinting XIONG , Zhiqiang XIONG , Panlei XIAO , Xuliang NIE , Xiuying SONG , Xiuguang YI . Synthesis, crystal structures, Hirshfeld surface analysis, and antifungal activity of two complexes Na(Ⅰ)/Cd(Ⅱ) assembled by 5-bromo-2-hydroxybenzoic acid ligands. Chinese Journal of Inorganic Chemistry, 2024, 40(9): 1661-1670. doi: 10.11862/CJIC.20240145
2. [2]
  Jiaming Xu , Yu Xiang , Weisheng Lin , Zhiwei Miao . Research Progress in the Synthesis of Cyclic Organic Compounds Using Bimetallic Relay Catalytic Strategies. University Chemistry, 2024, 39(3): 239-257. doi: 10.3866/PKU.DXHX202309093
3. [3]
  Yongqing Kuang , Jie Liu , Jianjun Feng , Wen Yang , Shuanglian Cai , Ling Shi . Experimental Design for the Two-Step Synthesis of Paracetamol from 4-Hydroxyacetophenone. University Chemistry, 2024, 39(8): 331-337. doi: 10.12461/PKU.DXHX202403012
4. [4]
  Danqing Wu , Jiajun Liu , Tianyu Li , Dazhen Xu , Zhiwei Miao . Research Progress on the Simultaneous Construction of C—O and C—X Bonds via 1,2-Difunctionalization of Olefins through Radical Pathways. University Chemistry, 2024, 39(11): 146-157. doi: 10.12461/PKU.DXHX202403087
5. [5]
  Yinwu Su , Xuanwen Zheng , Jianghui Du , Boda Li , Tao Wang , Zhiyan Huang . Green Synthesis of 1,3-Dibromoacetone Using Halogen Exchange Method: Recommending a Basic Organic Synthesis Teaching Experiment. University Chemistry, 2024, 39(5): 307-314. doi: 10.3866/PKU.DXHX202311092
6. [6]
  Yufang GAO , Nan HOU , Yaning LIANG , Ning LI , Yanting ZHANG , Zelong LI , Xiaofeng LI . Nano-thin layer MCM-22 zeolite: Synthesis and catalytic properties of trimethylbenzene isomerization reaction. Chinese Journal of Inorganic Chemistry, 2024, 40(6): 1079-1087. doi: 10.11862/CJIC.20240036
7. [7]
  Jianyu Qin , Yuejiao An , Yanfeng Zhang . In Situ Assembled ZnWO₄/g-C₃N₄ S-Scheme Heterojunction with Nitrogen Defect for CO₂ Photoreduction. Acta Physico-Chimica Sinica, 2024, 40(12): 2408002-. doi: 10.3866/PKU.WHXB202408002
8. [8]
  Wei Zhong , Dan Zheng , Yuanxin Ou , Aiyun Meng , Yaorong Su . K原子掺杂高度面间结晶的g-C₃N₄光催化剂及其高效H₂O₂光合成. Acta Physico-Chimica Sinica, 2024, 40(11): 2406005-. doi: 10.3866/PKU.WHXB202406005
9. [9]
  Guoqiang Chen , Zixuan Zheng , Wei Zhong , Guohong Wang , Xinhe Wu . 熔融中间体运输导向合成富氨基g-C₃N₄纳米片用于高效光催化产H₂O₂. Acta Physico-Chimica Sinica, 2024, 40(11): 2406021-. doi: 10.3866/PKU.WHXB202406021
10. [10]
  Tianlong Zhang , Rongling Zhang , Hongsheng Tang , Yan Li , Hua Li . Online Monitoring and Mechanistic Analysis of 3,5-diamino-1,2,4-triazole (DAT) Synthesis via Raman Spectroscopy: A Recommendation for a Comprehensive Instrumental Analysis Experiment. University Chemistry, 2024, 39(6): 303-311. doi: 10.3866/PKU.DXHX202312006
11. [11]
  Minna Ma , Yujin Ouyang , Yuan Wu , Mingwei Yuan , Lijuan Yang . Green Synthesis of Medical Chemiluminescence Reagents by Photocatalytic Oxidation. University Chemistry, 2024, 39(5): 134-143. doi: 10.3866/PKU.DXHX202310093
12. [12]
  Qingying Gao , Tao Luo , Jianyuan Su , Chaofan Yu , Jiazhu Li , Bingfei Yan , Wenzuo Li , Zhen Zhang , Yi Liu . Refinement and Expansion of the Classic Cinnamic Acid Synthesis Experiment. University Chemistry, 2024, 39(5): 243-250. doi: 10.3866/PKU.DXHX202311074
13. [13]
  Wenjun Zheng . Application in Inorganic Synthesis of Ionic Liquids. University Chemistry, 2024, 39(8): 163-168. doi: 10.3866/PKU.DXHX202401020
14. [14]
  Hongyan Chen , Yajun Hou , Shui Hu , Zhuoxun Wei , Fang Zhu , Chengyong Su . Construction of Synthetic Chemistry Experiment of the Chemistry “101 Plan”. University Chemistry, 2024, 39(10): 58-63. doi: 10.12461/PKU.DXHX202409109
15. [15]
  Cunming Yu , Dongliang Tian , Jing Chen , Qinglin Yang , Kesong Liu , Lei Jiang . Chemistry “101 Program” Synthetic Chemistry Experiment Course Construction: Synthesis and Properties of Bioinspired Superhydrophobic Functional Materials. University Chemistry, 2024, 39(10): 101-106. doi: 10.12461/PKU.DXHX202408008
16. [16]
  Quanliang Chen , Zhaohui Zhou . Research on the Active Site of Nitrogenase over Fifty Years. University Chemistry, 2024, 39(7): 287-293. doi: 10.3866/PKU.DXHX202310133
17. [17]
  Yuan Zheng , Quan Lan , Zhenggen Zha , Lingling Li , Jun Jiang , Pingping Zhu . Teaching Reform of Organic Synthesis Experiments by Introducing Reverse Thinking and Design Concepts: Taking the Synthesis of Cinnamic Acid Based on Retrosynthetic Analysis as an Example. University Chemistry, 2024, 39(6): 207-213. doi: 10.3866/PKU.DXHX202310065
18. [18]
  Li Jiang , Changzheng Chen , Yang Su , Hao Song , Yanmao Dong , Yan Yuan , Li Li . Electrochemical Synthesis of Polyaniline and Its Anticorrosive Application: Improvement and Innovative Design of the “Chemical Synthesis of Polyaniline” Experiment. University Chemistry, 2024, 39(3): 336-344. doi: 10.3866/PKU.DXHX202309002
19. [19]
  Guangming YIN , Huaiyao WANG , Jianhua ZHENG , Xinyue DONG , Jian LI , Yi'nan SUN , Yiming GAO , Bingbing WANG . Preparation and photocatalytic degradation performance of Ag/protonated g-C₃N₄ nanorod materials. Chinese Journal of Inorganic Chemistry, 2024, 40(8): 1491-1500. doi: 10.11862/CJIC.20240086
20. [20]
  Zhiwen HU , Weixia DONG , Qifu BAO , Ping LI . Low-temperature synthesis of tetragonal BaTiO₃ for piezocatalysis. Chinese Journal of Inorganic Chemistry, 2024, 40(5): 857-866. doi: 10.11862/CJIC.20230462

Get Citation

PDF

XML

Metrics

PDF Downloads(16)
Abstract views(1177)
HTML views(326)

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142