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化学进展 2022, Vol. 34 Issue (7): 1548-1553 DOI: 10.7536/PC220231 前一篇   后一篇

• 综述 •

聚糖化学合成的挑战和可能的凝聚态化学问题

徐鹏*(), 俞飚*()   

  1. 中国科学院上海有机化学研究所 生命有机化学国家重点实验室 上海 200032
  • 收稿日期:2022-02-24 修回日期:2022-03-25 出版日期:2022-07-24 发布日期:2022-06-20
  • 通讯作者: 徐鹏, 俞飚
  • 基金资助:
    国家自然科学基金项目(22177125); 上海市科学技术委员会项目(22ZR1475600)
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Challenges in Chemical Synthesis of Glycans and the Possible Problems Relevant to Condensed Matter Chemistry

Peng Xu(), Biao Yu()   

  1. State Key Laboratory of Bioorganic and Natural Product Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Science,Shanghai 200032, China
  • Received:2022-02-24 Revised:2022-03-25 Online:2022-07-24 Published:2022-06-20
  • Contact: Peng Xu, Biao Yu
  • Supported by:
    the National Natural Science Foundation of China(22177125); Science and Technology Commission of Shanghai Municipality(22ZR1475600)

聚糖是自然界含量最丰富的有机高分子,是各类生命体中重要的结构支撑和能量储存物质;而且,细胞表面的聚糖在细胞识别、分化、发育、癌变和免疫等生命过程中发挥重要作用。相比于核酸和蛋白质,对于聚糖类功能的研究远远落后,这与难以获取结构明确的聚糖及缺乏在体内精确操控聚糖的手段相关。聚糖的合成化学在最近几十年里得到了飞速发展,为聚糖,特别是寡聚糖的结构和功能研究提供了强有力的工具。然而,相比于核酸和蛋白质的合成,聚糖的合成仍然效率低下,特别是对于其中一些具有特殊结构糖链的合成仍然是挑战性的课题。在聚糖的合成实验中,经常会出现意外的结果,多种因素可能影响特定糖苷键的合成效率和立体选择性。聚糖分子可以通过分子间非共价作用力形成聚集体,从而影响合成。特别是在脱除保护基的过程中,聚糖分子溶解性的巨大变化对反应历程产生决定性影响。这些由于聚集体形成而对反应性的影响尚没有深入研究;在具体合成中,仍然需要通过实验的不断试错来完成聚糖的合成。另外,生命体中的聚糖和糖缀合物也通过形成超分子结构来发挥功能。因此,研究聚糖和聚糖合成中的凝聚态化学具有重要意义。

关键词： 聚糖, 化学合成, 聚集体, 溶解度, 凝聚态化学

Glycans are the most abundant organic polymers in nature, and vital biomaterials for structural support and energy storage in living organisms. Meanwhile, glycans play an important role in cell recognition, differentiation, development, carcinogenesis and immunity. Compared with nucleic acid and protein, the specific role of glycans in many biological processes is still unknown, which is related to the difficulty of accessing well-defined glycans and the lack of precise tools for manipulating glycans in vivo. Synthetic methods in carbohydrate chemistry have been developed rapidly in recent decades, providing a powerful weapon for the study of synthetic glycans, especially oligosaccharides. Nevertheless, compared with the synthesis of nucleic acids and proteins, the synthesis of structurally well-defined glycans remains an unsolved chemical challenge with many unexpected problems. There are various factors that may affect the efficiency and stereoselectivity of glycosylation profile. Furthermore, glycans could be assembled into ordered aggregates through intermolecular non-covalent forces, then affecting the synthesis. For instance, in the process of removal protecting groups, the great change of solubility of glycan has a decisive effect on the reaction. The effect of aggregation formation on reactivity has not been thoroughly studied. Therefore, it is still necessary to complete the synthesis of well-defined glycan through trial-and-error experiments. In addition, glycans and glycoconjugates play an important role in living organisms by forming supramolecular structures. In conclusion, it is of great significance to study the condensed matter chemistry in glycans and their synthesis.

Contents

1 Structure, function and synthesis of glycans in living systems

2 Challenges and advances in the chemical synthesis of glycans

3 Some uncertainties in the chemical synthesis of glycans

3.1 The solvent effect

3.2 The concentration effect

3.3 The temperature effect

3.4 Problems in heterogeneous reactions

3.5 Solubility problem

4 Possible condensed matter chemistry problems

5 Prospect

Key words: glycans, chemical synthesis, aggregation, solubility, condensed matter chemistry
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图1 蛋白质的糖基化及其糖链介导的生命过程[2]
Fig. 1 Protein glycosylation and the glycan-involved interactions[2]
图2 缩聚反应制备聚糖[14]
Fig. 2 Glycan synthesis by condensation polymerization[14]. Ac = acetyl[14]
图3 α-葡聚十糖的浓度依赖性立体选择性合成[17]
Fig. 3 Stereoselective synthesis of α- decaglucan based on a concentration effect[17]. Bn = benzyl, Bz = benzoyl, Tol = p-methylphenyl
图4 模板导向的环合糖苷化反应中温度对立体化学的影响[21]
Fig. 4 Template directed cyclo-glycosylation with the stereoselectivity being effected by the reaction temperature[21]. Me = methyl, TBDPS = tert-butyldiphenylsilyl
图5 不同干燥剂存在下的1,2-顺式糖苷化反应[23]
Fig. 5 1,2-cis Selective glycosylation in the presence of different dehydrating agents[23]
图6 拟杆菌脂多糖O-抗原聚糖合成中的保护基脱除[25f]
Fig. 6 Deprotection of glycans relevant to the O-antigen of Bacteroides vulgatus[25f]. Ph = phenyl, TBS = tert-butyldimethyl, MP = p-methoxyphenyl
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