Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Exploiting non-covalent interactions in selective carbohydrate synthesis

Nature Reviews Chemistry volume 5, pages 792–815 (2021)Cite this article

Subjects

Abstract

Non-covalent interactions (NCIs) are a vital component of biological bond-forming events, and have found important applications in multiple branches of chemistry. In recent years, the biomimetic exploitation of NCIs in challenging glycosidic bond formation and glycofunctionalizations has attracted significant interest across diverse communities of organic and carbohydrate chemists. This emerging theme is a major new direction in contemporary carbohydrate chemistry, and is rapidly gaining traction as a robust strategy to tackle long-standing issues such as anomeric and site selectivity. This Review thus seeks to provide a bird’s-eye view of wide-ranging advances in harnessing NCIs within the broad field of synthetic carbohydrate chemistry. These include the exploitation of NCIs in non-covalent catalysed glycosylations, in non-covalent catalysed glycofunctionalizations, in aglycone delivery, in stabilization of intermediates and transition states, in the existence of intramolecular hydrogen bonding networks and in aggregation by hydrogen bonds. In addition, recent emerging opportunities in exploiting halogen bonding and other unconventional NCIs, such as CH–π, cation–π and cation–n interactions, in various aspects of carbohydrate chemistry are also examined.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Thiourea-catalysed glycosylations of glycals and trichloroacetimidates.
Fig. 2: (Thio)urea-catalysed Koenigs–Knorr glycosylation, strain release glycosylation and site-selective functionalization.
Fig. 3: Chiral phosphoric acid and non-thiourea hydrogen bonding-catalysed glycosylations and glycofunctionalizations.
Fig. 4: Non-hydrogen bonding non-covalent-catalysed glycosylations and site-selective functionalizations.
Fig. 5: Hydrogen bond-mediated aglycone delivery (HAD).
Fig. 6: Stabilization of intermediates and transition states by non-covalent interactions.
Fig. 7: The influences of non-covalent intramolecular networks on glycosylation reactivity and selectivity.
Fig. 8: Aggregation of saccharides by HB and its effect on reactivity and selectivity.

Similar content being viewed by others

References

  1. Bissantz, C., Kuhn, B. & Stahl, M. A medicinal chemist’s guide to molecular interactions. J. Med. Chem. 53, 5061–5084 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Hobza, P. & Řezáč, J. Introduction: noncovalent interactions. Chem. Rev. 116, 4911–4912 (2016).

    Article  CAS  PubMed  Google Scholar 

  3. Hunter, C. A. Quantifying intermolecular interactions: guidelines for the molecular recognition toolbox. Angew. Chem. Int. Ed. 43, 5310–5324 (2004).

    Article  CAS  Google Scholar 

  4. Jeffrey, G. A. & Saenger, W. Hydrogen Bonding in Biological Structures (Springer-Verlag, 1994).

  5. Knowles, R. R. & Jacobsen, E. N. Attractive noncovalent interactions in asymmetric catalysis: links between enzymes and small molecule catalysts. Proc. Natl Acad. Sci. USA 107, 20678–20685 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Mahadevi, A. S. & Sastry, G. N. Cooperativity in noncovalent interactions. Chem. Rev. 116, 2775–2825 (2016).

    Article  CAS  PubMed  Google Scholar 

  7. Mahmudov, K. T., Kopylovich, M. N., Guedes da Silva, M. F. C. & Pombeiro, A. J. L. Non-covalent interactions in the synthesis of coordination compounds: recent advances. Coord. Chem. Rev. 345, 54–72 (2017).

    Article  CAS  Google Scholar 

  8. Müller-Dethlefs, K. & Hobza, P. Noncovalent interactions:  a challenge for experiment and theory. Chem. Rev. 100, 143–168 (2000).

    Article  PubMed  Google Scholar 

  9. Neel, A. J., Hilton, M. J., Sigman, M. S. & Toste, F. D. Exploiting non-covalent π interactions for catalyst design. Nature 543, 637 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Scheiner, S. The pnicogen bond: its relation to hydrogen, halogen, and other noncovalent bonds. Acc. Chem. Res. 46, 280–288 (2013).

    Article  CAS  PubMed  Google Scholar 

  11. Peng, P. & Schmidt, R. R. Acid–base catalysis in glycosidations: a nature derived alternative to the generally employed methodology. Acc. Chem. Res. 50, 1171–1183 (2017).

    Article  CAS  PubMed  Google Scholar 

  12. Gloster, T. M. Advances in understanding glycosyltransferases from a structural perspective. Curr. Opin. Struct. Biol. 28, 131–141 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Lairson, L. L., Henrissat, B., Davies, G. J. & Withers, S. G. Glycosyltransferases: structures, functions, and mechanisms. Annu. Rev. Biochem. 77, 521–555 (2008).

    Article  CAS  PubMed  Google Scholar 

  14. Liang, D.-M. et al. Glycosyltransferases: mechanisms and applications in natural product development. Chem. Soc. Rev. 44, 8350–8374 (2015).

    Article  CAS  PubMed  Google Scholar 

  15. Nidetzky, B., Gutmann, A. & Zhong, C. Leloir glycosyltransferases as biocatalysts for chemical production. ACS Catal. 8, 6283–6300 (2018).

    Article  CAS  Google Scholar 

  16. Lobsanov, Y. D. et al. Structure of Kre2p/Mnt1p: a yeast α-1,2-mannosyltransferase involved in mannoprotein biosynthesis. J. Biol. Chem. 279, 17921–17931 (2004).

    Article  CAS  PubMed  Google Scholar 

  17. Imberty, A. & Pérez, S. Stereochemistry of the N-glycosylation sites in glycoproteins. Protein Eng. Des. Sel. 8, 699–709 (1995).

    Article  CAS  Google Scholar 

  18. Davis, J. T., Hirani, S., Bartlett, C. & Reid, B. R. 1H NMR studies on an Asn-linked glycopeptide. GlcNAc-1 C2-N2 bond is rigid in H2O. J. Biol. Chem. 269, 3331–3338 (1994).

    Article  CAS  PubMed  Google Scholar 

  19. Hudson, K. L. et al. Carbohydrate–aromatic interactions in proteins. J. Am. Chem. Soc. 137, 15152–15160 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Laughrey, Z. R., Kiehna, S. E., Riemen, A. J. & Waters, M. L. Carbohydrate−π interactions: what are they worth? J. Am. Chem. Soc. 130, 14625–14633 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Nishio, M. The CH/π hydrogen bond in chemistry. Conformation, supramolecules, optical resolution and interactions involving carbohydrates. Phys. Chem. Chem. Phys. 13, 13873–13900 (2011).

    Article  CAS  PubMed  Google Scholar 

  22. Nishio, M., Umezawa, Y., Fantini, J., Weiss, M. S. & Chakrabarti, P. CH–π hydrogen bonds in biological macromolecules. Phys. Chem. Chem. Phys. 16, 12648–12683 (2014).

    Article  CAS  PubMed  Google Scholar 

  23. Spiwok, V. CH/π interactions in carbohydrate recognition. Molecules 22, 1038 (2017).

    Article  PubMed Central  Google Scholar 

  24. Vyas, N. K. Atomic features of protein-carbohydrate interactions. Curr. Opin. Struct. Biol. 1, 732–740 (1991).

    Article  CAS  Google Scholar 

  25. Hsu, C.-H. et al. The dependence of carbohydrate–aromatic interaction strengths on the structure of the carbohydrate. J. Am. Chem. Soc. 138, 7636–7648 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Adero, P. O., Amarasekara, H., Wen, P., Bohé, L. & Crich, D. The experimental evidence in support of glycosylation mechanisms at the SN1–SN2 interface. Chem. Rev. 118, 8242–8284 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Bennett, C. S. & Galan, M. C. Methods for 2-deoxyglycoside synthesis. Chem. Rev. 118, 7931–7985 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Bohé, L. & Crich, D. A propos of glycosyl cations and the mechanism of chemical glycosylation; the current state of the art. Carbohydr. Res. 403, 48–59 (2015).

    Article  PubMed  Google Scholar 

  29. Boltje, T. J., Buskas, T. & Boons, G.-J. Opportunities and challenges in synthetic oligosaccharide and glycoconjugate research. Nat. Chem. 1, 611 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Danishefsky, S. J. & Bilodeau, M. T. Glycals in organic synthesis: the evolution of comprehensive strategies for the assembly of oligosaccharides and glycoconjugates of biological consequence. Angew. Chem. Int. Ed. Engl. 35, 1380–1419 (1996).

    Article  CAS  Google Scholar 

  31. Danishefsky, S. J., Shue, Y.-K., Chang, M. N. & Wong, C.-H. Development of Globo-H cancer vaccine. Acc. Chem. Res. 48, 643–652 (2015).

    Article  CAS  PubMed  Google Scholar 

  32. Das, R. & Mukhopadhyay, B. Chemical O-glycosylations: an overview. ChemistryOpen 5, 401–433 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Ling, J. & Bennett, C. S. Recent developments in stereoselective chemical glycosylation. Asian J. Org. Chem. 8, 802–813 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Nielsen, M. M. & Pedersen, C. M. Catalytic glycosylations in oligosaccharide synthesis. Chem. Rev. 118, 8285–8358 (2018).

    Article  CAS  PubMed  Google Scholar 

  35. Panza, M., Pistorio, S. G., Stine, K. J. & Demchenko, A. V. Automated chemical oligosaccharide synthesis: novel approach to traditional challenges. Chem. Rev. 118, 8105–8150 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Seeberger, P. H. The logic of automated glycan assembly. Acc. Chem. Res. 48, 1450–1463 (2015).

    Article  CAS  PubMed  Google Scholar 

  37. Walvoort, M. T. C. et al. The impact of oxacarbenium ion conformers on the stereochemical outcome of glycosylations. Carbohydr. Res. 345, 1252–1263 (2010).

    Article  CAS  PubMed  Google Scholar 

  38. Whitfield, D. M. Plausible transition states for glycosylation reactions. Carbohydr. Res. 356, 180–190 (2012).

    Article  CAS  PubMed  Google Scholar 

  39. Whitfield, D. M. & Guo, J. Proton transfer and hydrogen bonding in glycosylation reactions. J. Carbohydr. Chem. 36, 59–99 (2017).

    Article  CAS  Google Scholar 

  40. Yang, Y., Zhang, X. & Yu, B. O-Glycosylation methods in the total synthesis of complex natural glycosides. Nat. Prod. Rep. 32, 1331–1355 (2015).

    Article  CAS  PubMed  Google Scholar 

  41. Zhu, X. & Schmidt, R. R. New principles for glycoside-bond formation. Angew. Chem. Int. Ed. 48, 1900–1934 (2009).

    Article  CAS  Google Scholar 

  42. Balmond, E. I., Galan, M. C. & McGarrigle, E. M. Recent developments in the application of organocatalysis to glycosylations. Synlett 24, 2335–2339 (2013).

    Article  CAS  Google Scholar 

  43. Williams, R. & Galan, M. C. Recent advances in organocatalytic glycosylations. Eur. J. Org. Chem. 6247–6264 (2017).

  44. Davis, H. J. & Phipps, R. J. Harnessing non-covalent interactions to exert control over regioselectivity and site-selectivity in catalytic reactions. Chem. Sci. 8, 864–877 (2017).

    Article  CAS  PubMed  Google Scholar 

  45. Toste, F. D., Sigman, M. S. & Miller, S. J. Pursuit of noncovalent interactions for strategic site-selective catalysis. Acc. Chem. Res. 50, 609–615 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Proctor, R. S. J., Colgan, A. C. & Phipps, R. J. Exploiting attractive non-covalent interactions for the enantioselective catalysis of reactions involving radical intermediates. Nat. Chem. 12, 990–1004 (2020).

    Article  PubMed  Google Scholar 

  47. Crich, D. En route to the transformation of glycoscience: a chemist’s perspective on internal and external crossroads in glycochemistry. J. Am. Chem. Soc. 143, 17–34 (2021).

    Article  CAS  PubMed  Google Scholar 

  48. Whitfield, D. M. In a glycosylation reaction how does a hydroxylic nucleophile find the activated anomeric carbon? Carbohydr. Res. 403, 69–89 (2015).

    Article  CAS  PubMed  Google Scholar 

  49. Crini, G. Review: a history of cyclodextrins. Chem. Rev. 114, 10940–10975 (2014).

    Article  CAS  PubMed  Google Scholar 

  50. Szejtli, J. Introduction and general overview of cyclodextrin chemistry. Chem. Rev. 98, 1743–1754 (1998).

    Article  CAS  PubMed  Google Scholar 

  51. Asensio, J. L., Ardá, A., Cañada, F. J. & Jiménez-Barbero, J. Carbohydrate–aromatic interactions. Acc. Chem. Res. 46, 946–954 (2013).

    Article  CAS  PubMed  Google Scholar 

  52. Davis, A. P. Biomimetic carbohydrate recognition. Chem. Soc. Rev. 49, 2531–2545 (2020).

    Article  CAS  PubMed  Google Scholar 

  53. Davis, A. P. & Wareham, R. S. Carbohydrate recognition through noncovalent interactions: a challenge for biomimetic and supramolecular chemistry. Angew. Chem. Int. Ed. 38, 2978–2996 (1999).

    Article  CAS  Google Scholar 

  54. Mazik, M. Molecular recognition of carbohydrates by acyclic receptors employing noncovalent interactions. Chem. Soc. Rev. 38, 935–956 (2009).

    Article  CAS  PubMed  Google Scholar 

  55. Walker, D. B., Joshi, G. & Davis, A. P. Progress in biomimetic carbohydrate recognition. Cell. Mol. Life Sci. 66, 3177–3191 (2009).

    Article  CAS  PubMed  Google Scholar 

  56. Yu, Y. & Delbianco, M. Conformational studies of oligosaccharides. Chem. Eur. J. 26, 9814–9825 (2020).

    Article  CAS  PubMed  Google Scholar 

  57. Lawandi, J., Rocheleau, S. & Moitessier, N. Regioselective acylation, alkylation, silylation and glycosylation of monosaccharides. Tetrahedron 72, 6283–6319 (2016).

    Article  CAS  Google Scholar 

  58. Blaszczyk, S. A., Homan, T. C. & Tang, W. Recent advances in site-selective functionalization of carbohydrates mediated by organocatalysts. Carbohydr. Res. 471, 64–77 (2019).

    Article  CAS  PubMed  Google Scholar 

  59. Dimakos, V. & Taylor, M. S. Site-selective functionalization of hydroxyl groups in carbohydrate derivatives. Chem. Rev. 118, 11457–11517 (2018).

    Article  CAS  PubMed  Google Scholar 

  60. Huang, Z. & Dong, G. Site-selectivity control in organic reactions: a quest to differentiate reactivity among the same kind of functional groups. Acc. Chem. Res. 50, 465–471 (2017).

    Article  CAS  PubMed  Google Scholar 

  61. Shang, W., He, B. & Niu, D. Ligand-controlled, transition-metal catalysed site-selective modification of glycosides. Carbohydr. Res. 474, 16–33 (2019).

    Article  CAS  PubMed  Google Scholar 

  62. Song, W. & Zheng, N. Chiral catalyst-directed site-selective functionalization of hydroxyl groups in carbohydrates. J. Carbohydr. Chem. 36, 143–161 (2017).

    Article  CAS  Google Scholar 

  63. Jäger, M. & Minnaard, A. J. Regioselective modification of unprotected glycosides. Chem. Commun. 52, 656–664 (2016).

    Article  Google Scholar 

  64. Levi, S. M. & Jacobsen, E. N. Catalyst-controlled glycosylations. Org. React. 100, 801–852 (2019).

    CAS  Google Scholar 

  65. Connon, S. J. Organocatalysis mediated by (thio)urea derivatives. Chem. Eur. J. 12, 5418–5427 (2006).

    Article  PubMed  Google Scholar 

  66. Doyle, A. G. & Jacobsen, E. N. Small-molecule H-bond donors in asymmetric catalysis. Chem. Rev. 107, 5713–5743 (2007).

    Article  CAS  PubMed  Google Scholar 

  67. Schreiner, P. R. Metal-free organocatalysis through explicit hydrogen bonding interactions. Chem. Soc. Rev. 32, 289–296 (2003).

    Article  CAS  PubMed  Google Scholar 

  68. Takemoto, Y. Development of chiral thiourea catalysts and its application to asymmetric catalytic reactions. Chem. Pharm. Bull. 58, 593–601 (2010).

    Article  CAS  Google Scholar 

  69. Reisman, S. E., Doyle, A. G. & Jacobsen, E. N. Enantioselective thiourea-catalyzed additions to oxocarbenium ions. J. Am. Chem. Soc. 130, 7198–7199 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Balmond, E. I., Coe, D. M., Galan, M. C. & McGarrigle, E. M. α-Selective organocatalytic synthesis of 2-deoxygalactosides. Angew. Chem. Int. Ed. 51, 9152–9155 (2012).

    Article  CAS  Google Scholar 

  71. Kotke, M. & Schreiner, P. R. Generally applicable organocatalytic tetrahydropyranylation of hydroxy functionalities with very low catalyst loading. Synthesis 2007, 779–790 (2007).

    Article  Google Scholar 

  72. Larsen, D., Langhorn, L. M., Akselsen, O. M., Nielsen, B. E. & Pittelkow, M. Thiosemicarbazone organocatalysis: tetrahydropyranylation and 2-deoxygalactosylation reactions and kinetics-based mechanistic investigation. Chem. Sci. 8, 7978–7982 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Madarász, Á. et al. Thiourea derivatives as Brønsted acid organocatalysts. ACS Catal. 6, 4379–4387 (2016).

    Article  Google Scholar 

  74. Smajlagic, I., Durán, R., Pilkington, M. & Dudding, T. Cyclopropenium enhanced thiourea catalysis. J. Org. Chem. 83, 13973–13980 (2018).

    Article  CAS  PubMed  Google Scholar 

  75. Bradshaw, G. A. et al. Stereoselective organocatalysed glycosylations – thiouracil, thioureas and monothiophthalimide act as Brønsted acid catalysts at low loadings. Chem. Sci. 10, 508–514 (2019).

    Article  CAS  PubMed  Google Scholar 

  76. Palo-Nieto, C., Sau, A., Williams, R. & Galan, M. C. Cooperative Brønsted acid-type organocatalysis for the stereoselective synthesis of deoxyglycosides. J. Org. Chem. 82, 407–414 (2017).

    Article  CAS  PubMed  Google Scholar 

  77. Dubey, A., Sangwan, R. & Mandal, P. K. N-benzoylglycine/thiourea cooperative catalysed stereoselective O-glycosidation: activation of O-glycosyl trichloroacetimidate donors. Catal. Commun. 125, 123–129 (2019).

    Article  CAS  Google Scholar 

  78. Geng, Y. et al. Cooperative catalysis in glycosidation reactions with o-glycosyl trichloroacetimidates as glycosyl donors. Angew. Chem. Int. Ed. 52, 10089–10092 (2013).

    Article  CAS  Google Scholar 

  79. Peng, P., Geng, Y., Göttker-Schnetmann, I. & Schmidt, R. R. 2-Nitro-thioglycosides: α- and β-selective generation and their potential as β-selective glycosyl donors. Org. Lett. 17, 1421–1424 (2015).

    Article  CAS  PubMed  Google Scholar 

  80. Yoshida, K., Kanoko, Y. & Takao, K. Kinetically controlled α-selective o-glycosylation of phenol derivatives using 2-nitroglycals by a bifunctional chiral thiourea catalyst. Asian J. Org. Chem. 5, 1230–1236 (2016).

    Article  CAS  Google Scholar 

  81. Medina, S. et al. Stereoselective glycosylation of 2-nitrogalactals catalyzed by a bifunctional organocatalyst. Org. Lett. 18, 4222–4225 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Blažek Bregović, V., Basarić, N. & Mlinarić-Majerski, K. Anion binding with urea and thiourea derivatives. Coord. Chem. Rev. 295, 80–124 (2015).

    Article  Google Scholar 

  83. Busschaert, N., Caltagirone, C., Van Rossom, W. & Gale, P. A. Applications of supramolecular anion recognition. Chem. Rev. 115, 8038–8155 (2015).

    Article  CAS  PubMed  Google Scholar 

  84. Gómez, D. E., Fabbrizzi, L., Licchelli, M. & Monzani, E. Urea vs. thiourea in anion recognition. Org. Biomol. Chem. 3, 1495–1500 (2005).

    Article  PubMed  Google Scholar 

  85. Molina, P., Zapata, F. & Caballero, A. Anion recognition strategies based on combined noncovalent interactions. Chem. Rev. 117, 9907–9972 (2017).

    Article  CAS  PubMed  Google Scholar 

  86. Sun, L., Wu, X., Xiong, D.-C. & Ye, X.-S. Stereoselective Koenigs–Knorr glycosylation catalyzed by urea. Angew. Chem. Int. Ed. 55, 8041–8044 (2016).

    Article  CAS  Google Scholar 

  87. Park, Y. et al. Macrocyclic bis-thioureas catalyse stereospecific glycosylation reactions. Science 355, 162–166 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Levi, S. M., Li, Q., Rötheli, A. R. & Jacobsen, E. N. Catalytic activation of glycosyl phosphates for stereoselective coupling reactions. Proc. Natl Acad. Sci. USA 116, 35–39 (2019).

    Article  CAS  PubMed  Google Scholar 

  89. Mayfield, A. B., Metternich, J. B., Trotta, A. H. & Jacobsen, E. N. Stereospecific furanosylations catalyzed by bis-thiourea hydrogen-bond donors. J. Am. Chem. Soc. 142, 4061–4069 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Li, Q., Levi, S. M. & Jacobsen, E. N. Highly selective β-mannosylations and β-rhamnosylations catalyzed by bis-thiourea. J. Am. Chem. Soc. 142, 11865–11872 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Fan, Y. & Kass, S. R. Electrostatically enhanced thioureas. Org. Lett. 18, 188–191 (2016).

    Article  CAS  PubMed  Google Scholar 

  92. Cousins, G. S. & Hoberg, J. O. Synthesis and chemistry of cyclopropanated carbohydrates. Chem. Soc. Rev. 29, 165–174 (2000).

    Article  CAS  Google Scholar 

  93. Xu, C. & Loh, C. C. J. An ultra-low thiourea catalysed strain-release glycosylation and a multicatalytic diversification strategy. Nat. Commun. 9, 4057 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  94. Li, T. et al. Catalytic regioselective benzoylation of 1,2-trans-diols in carbohydrates with benzoyl cyanide: the axial oxy group effect and the action of achiral and chiral amine catalysts. ACS Catal. 10, 11406–11416 (2020).

    Article  CAS  Google Scholar 

  95. Peng, P., Linseis, M., Winter, R. F. & Schmidt, R. R. Regioselective acylation of diols and triols: the cyanide effect. J. Am. Chem. Soc. 138, 6002–6009 (2016).

    Article  CAS  PubMed  Google Scholar 

  96. Li, T. et al. Regioselective benzoylation of unprotected β-glycopyranosides with benzoyl cyanide and an amine catalyst–application to saponin synthesis. Org. Chem. Front. 8, 260–265 (2020).

    Article  Google Scholar 

  97. Akiyama, T. Stronger Brønsted acids. Chem. Rev. 107, 5744–5758 (2007).

    Article  CAS  PubMed  Google Scholar 

  98. Terada, M. Chiral phosphoric acids as versatile catalysts for enantioselective transformations. Synthesis 2010, 1929–1982 (2010).

    Article  Google Scholar 

  99. Rueping, M., Nachtsheim, B. J., Ieawsuwan, W. & Atodiresei, I. Modulating the acidity: highly acidic Brønsted acids in asymmetric catalysis. Angew. Chem. Int. Ed. 50, 6706–6720 (2011).

    Article  CAS  Google Scholar 

  100. Parmar, D., Sugiono, E., Raja, S. & Rueping, M. Complete field guide to asymmetric BINOL-phosphate derived Brønsted acid and metal catalysis: history and classification by mode of activation; Brønsted acidity, hydrogen bonding, ion pairing, and metal phosphates. Chem. Rev. 114, 9047–9153 (2014).

    Article  CAS  PubMed  Google Scholar 

  101. James, T., van Gemmeren, M. & List, B. Development and applications of disulfonimides in enantioselective organocatalysis. Chem. Rev. 115, 9388–9409 (2015).

    Article  CAS  PubMed  Google Scholar 

  102. Cox, D. J., Smith, M. D. & Fairbanks, A. J. Glycosylation catalyzed by a chiral Brønsted acid. Org. Lett. 12, 1452–1455 (2010).

    Article  CAS  PubMed  Google Scholar 

  103. Kimura, T., Sekine, M., Takahashi, D. & Toshima, K. Chiral Brønsted acid mediated glycosylation with recognition of alcohol chirality. Angew. Chem. Int. Ed. 52, 12131–12134 (2013).

    Article  CAS  Google Scholar 

  104. Liu, D., Sarrafpour, S., Guo, W., Goulart, B. & Bennett, C. S. Matched/mismatched interactions in chiral Brønsted acid-catalyzed glycosylation reactions with 2-deoxy-sugar trichloroacetimidate donors. J. Carbohydr. Chem. 33, 423–434 (2014).

    Article  Google Scholar 

  105. Mensah, E., Camasso, N., Kaplan, W. & Nagorny, P. Chiral phosphoric acid directed regioselective acetalization of carbohydrate-derived 1,2-diols. Angew. Chem. Int. Ed. 52, 12932–12936 (2013).

    Article  CAS  Google Scholar 

  106. Lee, J., Borovika, A., Khomutnyk, Y. & Nagorny, P. Chiral phosphoric acid-catalysed desymmetrizative glycosylation of 2-deoxystreptamine and its application to aminoglycoside synthesis. Chem. Commun. 53, 8976–8979 (2017).

    Article  CAS  Google Scholar 

  107. Tay, J.-H. et al. Regiodivergent glycosylations of 6-deoxy-erythronolide B and oleandomycin-derived macrolactones enabled by chiral acid catalysis. J. Am. Chem. Soc. 139, 8570–8578 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Ghosh, T., Mukherji, A. & Kancharla, P. K. Sterically hindered 2,4,6-tri-tert-butylpyridinium salts as single hydrogen bond donors for highly stereoselective glycosylation reactions of glycals. Org. Lett. 21, 3490–3495 (2019).

    Article  CAS  PubMed  Google Scholar 

  109. Mukherji, A. & Kancharla, P. K. C–H…anion interactions assisted addition of water to glycals by sterically hindered 2,4,6-tri-tert-butylpyridinium hydrochloride. Org. Lett. 22, 2191–2195 (2020).

    Article  CAS  PubMed  Google Scholar 

  110. Kawabata, T., Muramatsu, W., Nishio, T., Shibata, T. & Schedel, H. A catalytic one-step process for the chemo-and regioselective acylation of monosaccharides. J. Am. Chem. Soc. 129, 12890–12895 (2007).

    Article  CAS  PubMed  Google Scholar 

  111. Ueda, Y., Furuta, T. & Kawabata, T. Final-stage site-selective acylation for the total syntheses of multifidosides A–C. Angew. Chem. Int. Ed. 54, 11966–11970 (2015).

    Article  CAS  Google Scholar 

  112. Shibayama, H., Ueda, Y., Tanaka, T. & Kawabata, T. Seven-step stereodivergent total syntheses of punicafolin and macaranganin. J. Am. Chem. Soc. 143, 1428–1434 (2021).

    Article  CAS  PubMed  Google Scholar 

  113. Sun, X., Lee, H., Lee, S. & Tan, K. L. Catalyst recognition of cis-1,2-diols enables site-selective functionalization of complex molecules. Nat. Chem. 5, 790–795 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Blaisdell, T. P., Lee, S., Kasaplar, P., Sun, X. & Tan, K. L. Practical silyl protection of ribonucleosides. Org. Lett. 15, 4710–4713 (2013).

    Article  CAS  PubMed  Google Scholar 

  115. Lee, S., Blaisdell, T. P., Kasaplar, P., Sun, X. & Tan, K. L. Synthesis of 5′-O-DMT-2′-O-TBS mononucleosides using an organic catalyst. Curr. Protoc. Nucleic Acid. Chem. 57, 2.17.11–12.17.11 (2014).

    Article  Google Scholar 

  116. Ren, B., Rahm, M., Zhang, X., Zhou, Y. & Dong, H. Regioselective acetylation of diols and polyols by acetate catalysis: mechanism and application. J. Org. Chem. 79, 8134–8142 (2014).

    Article  CAS  PubMed  Google Scholar 

  117. Zhang, X., Ren, B., Ge, J., Pei, Z. & Dong, H. A green and convenient method for regioselective mono and multiple benzoylation of diols and polyols. Tetrahedron 72, 1005–1010 (2016).

    Article  CAS  Google Scholar 

  118. Griswold, K. S. & Miller, S. J. A peptide-based catalyst approach to regioselective functionalization of carbohydrates. Tetrahedron 59, 8869–8875 (2003).

    Article  CAS  Google Scholar 

  119. Huber, F. & Kirsch, S. F. Site-selective acylations with tailor-made catalysts. Chem. Eur. J. 22, 5914–5918 (2016).

    Article  CAS  PubMed  Google Scholar 

  120. Beale, T. M., Chudzinski, M. G., Sarwar, M. G. & Taylor, M. S. Halogen bonding in solution: thermodynamics and applications. Chem. Soc. Rev. 42, 1667–1680 (2013).

    Article  CAS  PubMed  Google Scholar 

  121. Cavallo, G. et al. The halogen bond. Chem. Rev. 116, 2478–2601 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Costa Paulo, J. The halogen bond: nature and applications. Phys. Sci. Rev. 2, 20170136 (2017).

    Google Scholar 

  123. Lim, J. Y. C. & Beer, P. D. Sigma-hole interactions in anion recognition. Chem 4, 731–783 (2018).

    Article  CAS  Google Scholar 

  124. Mukherjee, A., Tothadi, S. & Desiraju, G. R. Halogen bonds in crystal engineering: like hydrogen bonds yet different. Acc. Chem. Res. 47, 2514–2524 (2014).

    Article  CAS  PubMed  Google Scholar 

  125. Scholfield, M. R., Zanden, C. M. V., Carter, M. & Ho, P. S. Halogen bonding (X-bonding): a biological perspective. Protein Sci. 22, 139–152 (2013).

    Article  CAS  PubMed  Google Scholar 

  126. Auffinger, P., Hays, F. A., Westhof, E. & Ho, P. S. Halogen bonds in biological molecules. Proc. Natl Acad. Sci. USA 101, 16789–16794 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Persch, E., Dumele, O. & Diederich, F. Molecular recognition in chemical and biological systems. Angew. Chem. Int. Ed. 54, 3290–3327 (2015).

    Article  CAS  Google Scholar 

  128. Wilcken, R., Zimmermann, M. O., Lange, A., Joerger, A. C. & Boeckler, F. M. Principles and applications of halogen bonding in medicinal chemistry and chemical biology. J. Med. Chem. 56, 1363–1388 (2013).

    Article  CAS  PubMed  Google Scholar 

  129. Tepper, R. & Schubert, U. S. Halogen bonding in solution: anion recognition, templated self-assembly, and organocatalysis. Angew. Chem. Int. Ed. 57, 6004–6016 (2018).

    Article  CAS  Google Scholar 

  130. Bulfield, D. & Huber, S. M. Halogen bonding in organic synthesis and organocatalysis. Chem. Eur. J. 22, 14434–14450 (2016).

    Article  CAS  PubMed  Google Scholar 

  131. Sutar, R. L. & Huber, S. M. Catalysis of organic reactions through halogen bonding. ACS Catal. 9, 9622–9639 (2019).

    Article  CAS  Google Scholar 

  132. Castelli, R. et al. Activation of glycosyl halides by halogen bonding. Chem. Asian J. 9, 2095–2098 (2014).

    Article  CAS  PubMed  Google Scholar 

  133. Kobayashi, Y., Nakatsuji, Y., Li, S., Tsuzuki, S. & Takemoto, Y. Direct N-glycofunctionalization of amides with glycosyl trichloroacetimidate by thiourea/halogen bond donor co-catalysis. Angew. Chem. Int. Ed. 57, 3646–3650 (2018).

    Article  CAS  Google Scholar 

  134. Li, S., Kobayashi, Y. & Takemoto, Y. Organocatalytic direct α-selective N-glycosylation of amide with glycosyl trichloroacetimidate. Chem. Pharm. Bull. 66, 768–770 (2018).

    Article  CAS  Google Scholar 

  135. Xu, C. & Loh, C. C. J. A multistage halogen bond catalyzed strain-release glycosylation unravels new hedgehog signaling inhibitors. J. Am. Chem. Soc. 141, 5381–5391 (2019).

    Article  CAS  PubMed  Google Scholar 

  136. Xu, C., Rao, V. U. B., Weigen, J. & Loh, C. C. J. A robust and tunable halogen bond organocatalysed 2-deoxyglycosylation involving quantum tunneling. Nat. Commun. 11, 4911 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  137. Balmond, E. I. et al. A 3,4-trans-fused cyclic protecting group facilitates α-selective catalytic synthesis of 2-deoxyglycosides. Angew. Chem. Int. Ed. 53, 8190–8194 (2014).

    Article  CAS  Google Scholar 

  138. Xiao, G. et al. Catalytic site-selective acylation of carbohydrates directed by cation–n interaction. J. Am. Chem. Soc. 139, 4346–4349 (2017).

    Article  CAS  PubMed  Google Scholar 

  139. Blaszczyk, S. A. et al. S-Adamantyl group directed site-selective acylation: applications in streamlined assembly of oligosaccharides. Angew. Chem. Int. Ed. 58, 9542–9546 (2019).

    Article  CAS  Google Scholar 

  140. Yasomanee, J. P. & Demchenko, A. V. Effect of remote picolinyl and picoloyl substituents on the stereoselectivity of chemical glycosylation. J. Am. Chem. Soc. 134, 20097–20102 (2012).

    Article  CAS  PubMed  Google Scholar 

  141. Yasomanee, J. P. & Demchenko, A. V. Hydrogen-bond-mediated aglycone delivery (HAD): a highly stereoselective synthesis of 1,2-cis α-d-glucosides from common glycosyl donors in the presence of bromine. Chem. Eur. J. 21, 6572–6581 (2015).

    Article  CAS  PubMed  Google Scholar 

  142. Khanam, A. & Kumar Mandal, P. Influence of remote picolinyl and picoloyl stereodirecting groups for the stereoselective glycosylation. Asian J. Org. Chem. 10, 296–314 (2021).

    Article  CAS  Google Scholar 

  143. Mannino, M. P., Yasomanee, J. P. & Demchenko, A. V. Investigation of the H-bond-mediated aglycone delivery reaction in application to the synthesis of β-glucosides. Carbohydr. Res. 470, 1–7 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Yasomanee, J. P. & Demchenko, A. V. Hydrogen bond mediated aglycone delivery: synthesis of linear and branched α-glucans. Angew. Chem. Int. Ed. 53, 10453–10456 (2014).

    Article  CAS  Google Scholar 

  145. Ruei, J.-H., Venukumar, P., Ingle, A. B. & Mong, K.-K. T. C6 picoloyl protection: a remote stereodirecting group for 2-deoxy-β-glycoside formation. Chem. Commun. 51, 5394–5397 (2015).

    Article  CAS  Google Scholar 

  146. Escopy, S., Geringer, S. A. & De Meo, C. Combined effect of the picoloyl protecting group and triflic acid in sialylation. Org. Lett. 19, 2638–2641 (2017).

    Article  CAS  PubMed  Google Scholar 

  147. Wu, Y.-F. & Tsai, Y.-F. Assistance of the C-7,8-picoloyl moiety for directing the glycosyl acceptors into the α-orientation for the glycosylation of sialyl donors. Org. Lett. 19, 4171–4174 (2017).

    Article  CAS  PubMed  Google Scholar 

  148. Jones, B. et al. Comparative study on the effects of picoloyl groups in sialylations based on their substitution pattern. J. Org. Chem. 84, 15052–15062 (2019).

    Article  CAS  PubMed  Google Scholar 

  149. Liu, D.-M., Wang, H.-L., Lei, J.-C., Zhou, X.-Y. & Yang, J.-S. A highly α-stereoselective sialylation method using 4-O-4-nitropicoloyl thiosialoside donor. Eur. J. Org. Chem. 575–585 (2020).

  150. Liu, Q.-W., Bin, H.-C. & Yang, J.-S. β-Arabinofuranosylation using 5-O-(2-quinolinecarbonyl) substituted ethyl thioglycoside donors. Org. Lett. 15, 3974–3977 (2013).

    Article  CAS  PubMed  Google Scholar 

  151. Gao, P.-C., Zhu, S.-Y., Cao, H. & Yang, J.-S. Total synthesis of marine glycosphingolipid vesparioside B. J. Am. Chem. Soc. 138, 1684–1688 (2016).

    Article  CAS  PubMed  Google Scholar 

  152. Huang, W. et al. Stereodirecting effect of C5-carboxylate substituents on the glycosylation stereochemistry of 3-deoxy-d-manno-oct-2-ulosonic acid (Kdo) thioglycoside donors: stereoselective synthesis of α- and β-Kdo glycosides. J. Am. Chem. Soc. 140, 3574–3582 (2018).

    Article  CAS  PubMed  Google Scholar 

  153. Lei, J.-C., Ruan, Y.-X., Luo, S. & Yang, J.-S. Stereodirecting effect of C3-ester groups on the glycosylation stereochemistry of l-rhamnopyranose thioglycoside donors: stereoselective synthesis of α- and β-l-rhamnopyranosides. Eur. J. Org. Chem. 6377–6382 (2019).

  154. Behera, A., Rai, D., Kushwaha, D. & Kulkarni, S. S. Total synthesis of trisaccharide repeating unit of O-specific polysaccharide of pseudomonas fluorescens BIM B-582. Org. Lett. 20, 5956–5959 (2018).

    Article  CAS  PubMed  Google Scholar 

  155. Dubey, A., Tiwari, A. & Mandal, P. K. An eco-friendly N-benzoylglycine/thiourea cooperative catalysed stereoselective synthesis of β-l-rhamnopyranosides. Carbohydr. Res. 487, 107887 (2020).

    Article  CAS  PubMed  Google Scholar 

  156. Li, H.-Z., Ding, J., Cheng, C.-R., Chen, Y. & Liang, X.-Y. β-l-Arabinofuranosylation conducted by 5-O-(2-pyridinecarbonyl)-l-arabinofuranosyl trichloroacetimidate. Carbohydr. Res. 460, 1–7 (2018).

    Article  CAS  PubMed  Google Scholar 

  157. Wang, P. et al. Hydrogen-bond-mediated aglycone delivery: synthesis of β-d-fructofuranosides. Org. Lett. 22, 2967–2971 (2020).

    Article  CAS  PubMed  Google Scholar 

  158. Norsikian, S. et al. Total synthesis of tiacumicin B: implementing hydrogen bond directed acceptor delivery for highly selective β-glycosylations. Angew. Chem. Int. Ed. 59, 6612–6616 (2020).

    Article  CAS  Google Scholar 

  159. Tresse, C. et al. Total synthesis of tiacumicin B: study of the challenging β-selective glycosylations. Chem. Eur. J. 27, 5230–5239 (2021).

    Article  CAS  PubMed  Google Scholar 

  160. Rönnols, J., Walvoort, M. T. C., van der Marel, G. A., Codée, J. D. C. & Widmalm, G. Chair interconversion and reactivity of mannuronic acid esters. Org. Biomol. Chem. 11, 8127–8134 (2013).

    Article  PubMed  Google Scholar 

  161. Yu, F. et al. Phenanthroline-catalyzed stereoretentive glycosylations. Angew. Chem. Int. Ed. 58, 6957–6961 (2019).

    Article  CAS  Google Scholar 

  162. Fang, T., Gu, Y., Huang, W. & Boons, G.-J. Mechanism of glycosylation of anomeric sulfonium ions. J. Am. Chem. Soc. 138, 3002–3011 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  163. Ding, F., Ishiwata, A. & Ito, Y. Bimodal glycosyl donors protected by 2-O-(ortho-tosylamido)benzyl group. Org. Lett. 20, 4384–4388 (2018).

    Article  CAS  PubMed  Google Scholar 

  164. Ding, F., Ishiwata, A. & Ito, Y. Stereodivergent mannosylation using 2-O-(ortho-tosylamido)benzyl group. Org. Lett. 20, 4833–4837 (2018).

    Article  CAS  PubMed  Google Scholar 

  165. Ding, F., Ishiwata, A., Zhou, S., Zhong, X. & Ito, Y. Unified strategy toward stereocontrolled assembly of various glucans based on bimodal glycosyl donors. J. Org. Chem. 85, 5536–5558 (2020).

    Article  CAS  PubMed  Google Scholar 

  166. Zeng, J. et al. Hydrogen-bonding-assisted exogenous nucleophilic reagent effect for β-selective glycosylation of rare 3-amino sugars. J. Am. Chem. Soc. 141, 8509–8515 (2019).

    Article  CAS  PubMed  Google Scholar 

  167. Zeng, J. et al. 3-Aminodeoxypyranoses in glycosylation: diversity-oriented synthesis and assembly in oligosaccharides. Angew. Chem. Int. Ed. 56, 5227–5231 (2017).

    Article  CAS  Google Scholar 

  168. Montalvillo-Jiménez, L. et al. Impact of aromatic stacking on glycoside reactivity: balancing CH/π and cation/π interactions for the stabilization of glycosyl-oxocarbenium ions. J. Am. Chem. Soc. 141, 13372–13384 (2019).

    Article  PubMed  Google Scholar 

  169. Richardson, A. C. & Williams, J. M. Selective acylation of pyranosides — II.: benzoylation of methyl 6-deoxy-α-l-galactopyranoside and methyl 6-deoxy-α-l-mannopyranoside. Tetrahedron 23, 1641–1646 (1967).

    Article  CAS  Google Scholar 

  170. Kondo, Y., Miyahara, K. & Kashimura, N. Selective benzoylation of methyl 6-deoxy-α- and β-d-glucopyranosides. Can. J. Chem. 51, 3272–3276 (1973).

    Article  CAS  Google Scholar 

  171. Muddasani, P. R., Bernet, B. & Vasella, A. Glycosylidene carbenes. Part 15. Synthesis of disaccharides from allopyranose-derived vicinal 1,2-diols. Evidence for the protonation by a H-bonded hydroxy group in the σ-plane of the intermediate carbene, followed by attack on the oxycarbenium ion in the π-plane. Helv. Chim. Acta 77, 334–350 (1994).

    Article  CAS  Google Scholar 

  172. Muddasani, P. R., Bozó, E., Bernet, B. & Vasella, A. Glycosylidene carbenes. Part 14. Glycosidation of partially protected galactopyranose-, glucopyranose-, and mannopyranose-derived vicinal diols. Helv. Chim. Acta 77, 257–290 (1994).

    Article  CAS  Google Scholar 

  173. Belén Cid, M., Alfonso, F., Alonso, I. & Martín-Lomas, M. On the origin of the regioselectivity in glycosylation reactions of 1,2-diols. Org. Biomol. Chem. 7, 1471–1481 (2009).

    Article  PubMed  Google Scholar 

  174. López de la Paz, M. et al. Carbohydrate hydrogen-bonding cooperativity − intramolecular hydrogen bonds and their cooperative effect on intermolecular processes−binding to a hydrogen-bond acceptor molecule. Eur. J. Org. Chem. 840–855 (2002).

  175. López de la Paz, M. & Vicent, C. Hydrogen bonding and cooperativity effects on the assembly of carbohydrates. Chem. Commun. 465–466 (1998).

  176. Vicente, V., Martin, J., Jiménez-Barbero, J., Chiara, J. L. & Vicent, C. Hydrogen-bonding cooperativity: using an intramolecular hydrogen bond to design a carbohydrate derivative with a cooperative hydrogen-bond donor centre. Chem. Eur. J. 10, 4240–4251 (2004).

    Article  CAS  PubMed  Google Scholar 

  177. Giuffredi, G. T., Gouverneur, V. & Bernet, B. Intramolecular OH…FC hydrogen bonding in fluorinated carbohydrates: CHF is a better hydrogen bond acceptor than CF2. Angew. Chem. Int. Ed. 52, 10524–10528 (2013).

    Article  CAS  Google Scholar 

  178. Kurahashi, T., Mizutani, T. & Yoshida, J.-I. Effect of intramolecular hydrogen-bonding network on the relative reactivities of carbohydrate OH groups. J. Chem. Soc. Perkin Trans. 1, 465–474 (1999).

    Article  Google Scholar 

  179. Kattnig, E. & Albert, M. Counterion-directed regioselective acetylation of octyl β-d-glucopyranoside. Org. Lett. 6, 945–948 (2004).

    Article  CAS  PubMed  Google Scholar 

  180. Magaud, D. et al. Differential reactivity of α- and β-anomers of glycosyl acceptors in glycosylations. a remote consequence of the endo-anomeric effect? Org. Lett. 2, 2275–2277 (2000).

    Article  CAS  PubMed  Google Scholar 

  181. Crich, D. & Dudkin, V. Why are the hydroxy groups of partially protected N-acetylglucosamine derivatives such poor glycosyl acceptors, and what can be done about it? A comparative study of the reactivity of N-acetyl-, N-phthalimido-, and 2-azido-2-deoxy-glucosamine derivatives in glycosylation. 2-Picolinyl ethers as reactivity-enhancing replacements for benzyl ethers. J. Am. Chem. Soc. 123, 6819–6825 (2001).

    Article  CAS  PubMed  Google Scholar 

  182. van der Vorm, S. et al. Acceptor reactivity in glycosylation reactions. Chem. Soc. Rev. 48, 4688–4706 (2019).

    Article  PubMed  Google Scholar 

  183. Moitessier, N., Englebienne, P. & Chapleur, Y. Directing-protecting groups for carbohydrates. Design, conformational study, synthesis and application to regioselective functionalization. Tetrahedron 61, 6839–6853 (2005).

    Article  CAS  Google Scholar 

  184. Lawandi, J., Rocheleau, S. & Moitessier, N. Directing/protecting groups mediate highly regioselective glycosylation of monoprotected acceptors. Tetrahedron 67, 8411–8420 (2011).

    Article  CAS  Google Scholar 

  185. Bohn, M. L., Colombo, M. I., Pisano, P. L., Stortz, C. A. & Rúveda, E. A. Differential O-3/O-4 regioselectivity in the glycosylation of α and β anomers of 6-O-substituted N-dimethylmaleoyl-protected d-glucosamine acceptors. Carbohydr. Res. 342, 2522–2536 (2007).

    Article  CAS  PubMed  Google Scholar 

  186. Bohn, M. L., Colombo, M. I., Rúveda, E. A. & Stortz, C. A. Conformational and electronic effects on the regioselectivity of the glycosylation of different anomers of N-dimethylmaleoyl-protected glucosamine acceptors. Org. Biomol. Chem. 6, 554–561 (2008).

    Article  CAS  PubMed  Google Scholar 

  187. Colombo, M. I., Rúveda, E. A., Gorlova, O., Lalancette, R. & Stortz, C. A. Structural analysis of methyl 6-O-benzyl-2-deoxy-2-dimethylmaleimido-α-d-allopyranoside by X-ray crystallography, NMR, and QM calculations: hydrogen bonding and comparison of density functionals. Carbohydr. Res. 353, 79–85 (2012).

    Article  CAS  PubMed  Google Scholar 

  188. Yu, J. et al. Synthetic access toward the diverse ginsenosides. Chem. Sci. 4, 3899–3905 (2013).

    Article  CAS  Google Scholar 

  189. Kuczynska, K. et al. Influence of intramolecular hydrogen bonds on regioselectivity of glycosylation. Synthesis of lupane-type saponins bearing the OSW-1 saponin disaccharide unit and its isomers. Carbohydr. Res. 423, 49–69 (2016).

    Article  CAS  PubMed  Google Scholar 

  190. Kononov, L. O. Chemical reactivity and solution structure: on the way to a paradigm shift? RSC Adv. 5, 46718–46734 (2015).

    Article  CAS  Google Scholar 

  191. Leys, J., Subramanian, D., Rodezno, E., Hammouda, B. & Anisimov, M. A. Mesoscale phenomena in solutions of 3-methylpyridine, heavy water, and an antagonistic salt. Soft Matter 9, 9326–9334 (2013).

    Article  CAS  Google Scholar 

  192. Li, Z. et al. Large-scale structures in tetrahydrofuran–water mixture with a trace amount of antioxidant butylhydroxytoluene (BHT). J. Phys. Chem. B 115, 7887–7895 (2011).

    Article  CAS  PubMed  Google Scholar 

  193. Sedlák, M. & Rak, D. Large-Scale inhomogeneities in solutions of low molar mass compounds and mixtures of liquids: supramolecular structures or nanobubbles? J. Phys. Chem. B 117, 2495–2504 (2013).

    Article  PubMed  Google Scholar 

  194. Sedlák, M. & Rak, D. On the origin of mesoscale structures in aqueous solutions of tertiary butyl alcohol: the mystery resolved. J. Phys. Chem. B 118, 2726–2737 (2014).

    Article  PubMed  Google Scholar 

  195. Subramanian, D. & Anisimov, M. A. Resolving the mystery of aqueous solutions of tertiary butyl alcohol. J. Phys. Chem. B 115, 9179–9183 (2011).

    Article  CAS  PubMed  Google Scholar 

  196. Subramanian, D. & Anisimov, M. A. Phase behavior and mesoscale solubilization in aqueous solutions of hydrotropes. Fluid Phase Equilib. 362, 170–176 (2014).

    Article  CAS  Google Scholar 

  197. Subramanian, D., Boughter, C. T., Klauda, J. B., Hammouda, B. & Anisimov, M. A. Mesoscale inhomogeneities in aqueous solutions of small amphiphilic molecules. Faraday Discuss. 167, 217–238 (2013).

    Article  PubMed  Google Scholar 

  198. Subramanian, D., Ivanov, D. A., Yudin, I. K., Anisimov, M. A. & Sengers, J. V. Mesoscale inhomogeneities in aqueous solutions of 3-methylpyridine and tertiary butyl alcohol. J. Chem. Eng. Data 56, 1238–1248 (2011).

    Article  CAS  Google Scholar 

  199. Subramanian, D., Klauda, J. B., Collings, P. J. & Anisimov, M. A. Mesoscale phenomena in ternary solutions of tertiary butyl alcohol, water, and propylene oxide. J. Phys. Chem. B 118, 5994–6006 (2014).

    Article  CAS  PubMed  Google Scholar 

  200. Zemb, T. & Kunz, W. Weak aggregation: State of the art, expectations and open questions. Curr. Opin. Colloid Interface Sci. 22, 113–119 (2016).

    Article  CAS  Google Scholar 

  201. Jawor-Baczynska, A., Moore, B. D., Lee, H. S., McCormick, A. V. & Sefcik, J. Population and size distribution of solute-rich mesospecies within mesostructured aqueous amino acid solutions. Faraday Discuss. 167, 425–440 (2013).

    Article  PubMed  Google Scholar 

  202. Kononov, L. O., Malysheva, N. N., Kononova, E. G. & Garkusha, O. G. The first example of synergism in glycosylation. Possible reasons and consequences. Russ. Chem. Bull. 55, 1311–1313 (2006).

    Article  CAS  Google Scholar 

  203. Kononov, L. O., Malysheva, N. N., Kononova, E. G. & Orlova, A. V. Intermolecular hydrogen-bonding pattern of a glycosyl donor: the key to understanding the outcome of sialylation. Eur. J. Org. Chem. 3251–3255 (2008).

  204. Kononov, L. O. et al. Concentration dependence of glycosylation outcome: a clue to reproducibility and understanding the reasons behind. Eur. J. Org. Chem. 1926–1934 (2012).

  205. Orlova, A. V., Tsvetkov, D. E. & Kononov, L. O. Separation of levoglucosan supramers by high performance liquid chromatography. Russ. Chem. Bull. 66, 1712–1715 (2017).

    Article  CAS  Google Scholar 

  206. Abronina, P. I., Zinin, A. I., Chizhov, A. O. & Kononov, L. O. Unusual outcome of glycosylation: hydrogen-bond mediated control of stereoselectivity by N-trifluoroacetyl group? Eur. J. Org. Chem. 4146–4160 (2020).

  207. Nagasaki, M. et al. Chemical synthesis of a complex-type N-glycan containing a core fucose. J. Org. Chem. 81, 10600–10616 (2016).

    Article  CAS  PubMed  Google Scholar 

  208. Zhou, J., Manabe, Y., Tanaka, K. & Fukase, K. Efficient synthesis of the disialylated tetrasaccharide motif in N-glycans through an amide-protection strategy. Chem. Asian J. 11, 1436–1440 (2016).

    Article  PubMed  Google Scholar 

  209. Uchinashi, Y., Nagasaki, M., Zhou, J., Tanaka, K. & Fukase, K. Reinvestigation of the C5-acetamide sialic acid donor for α-selective sialylation: practical procedure under microfluidic conditions. Org. Biomol. Chem. 9, 7243–7248 (2011).

    Article  CAS  PubMed  Google Scholar 

  210. Orlova, A. V., Laptinskaya, T. V., Bovin, N. V. & Kononov, L. O. Differences in reactivity of N-acetyl- and N,N-diacetylsialyl chlorides caused by their different supramolecular organization in solutions. Russ. Chem. Bull. 66, 2173–2179 (2017).

    Article  CAS  Google Scholar 

  211. Tsutsui, M. et al. Efficient synthesis of antigenic trisaccharides containing N-acetylglucosamine: protection of NHAc as NAc2. Eur. J. Org. Chem. 1802–1810 (2020).

  212. Nakatsuji, Y., Kobayashi, Y. & Takemoto, Y. Direct addition of amides to glycals enabled by solvation-insusceptible 2-haloazolium salt catalysis. Angew. Chem. Int. Ed. 58, 14115–14119 (2019).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The author acknowledges Fonds der Chemischen Industrie for generous research funding through a Liebig fellowship. The Boehringer Ingelheim Foundation is also gratefully acknowledged for the strong funding support of the exploitation of non-covalent interactions in carbohydrate chemistry through the Plus 3 Perspectives Programme. Further personnel funding through the Alexander von Humboldt Foundation and the Max Planck Society is acknowledged. C. Xu and V. U. B. Rao are gratefully acknowledged for their pioneering experimental contributions related to catalytic glycosylations that capitalize on non-covalent interactions as the activation mode in the author’s research group. H. Waldmann is greatly acknowledged for generous support and mentorship. The Max Planck Institute of Molecular Physiology and the Faculty of Chemistry and Chemical Biology of the Technische Universität Dortmund are also acknowledged for infrastructural and personnel support. This Review is dedicated to the memory of Professor Dieter Enders. The author thanks the anonymous reviewers for their constructive and thought-provoking comments, and apologizes to colleagues whose work was not cited due to selected coverage and space constraints.

Author information

Authors and Affiliations

  1. Max Planck Institüt für molekulare Physiologie, Dortmund, Germany

    Charles C. J. Loh

  2. Fakültät für Chemie und Chemische Biologie, Technische Universität Dortmund, Dortmund, Germany

    Charles C. J. Loh

Authors
  1. Charles C. J. Loh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Charles C. J. Loh.

Ethics declarations

Competing interests

The author declares no competing interests.

Additional information

Peer review information

Nature Reviews Chemistry thanks S. Vidal and the other anonymous reviewer(s) for their contribution to the peer review of this work.

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Glossary

Aglycone delivery

Conventionally an intramolecular synthetic strategy known as intramolecular aglycone delivery, used to dictate a 1,2-cis outcome from a two-step tethering–glycosylation sequence.

Site selectivity

A special case of chemoselectivity describing the differentiated reactivity among the similar functional groups in different chemical (often chiral) environments.

Anomeric selectivity

A term specific to carbohydrate chemistry that describes the diastereoselectivity at the anomeric centre upon the formation of a glycosidic bond.

Anomeric configuration

The stereochemical relationship between the anomeric centre and the configuration of the most distant stereogenic centre.

Catalyst control

The selectivity outcome of a reaction is determined by the Curtin–Hammett principle, through the difference in the energies of the catalyzed transition states leading to two or more stereoisomers.

Regioselectivity

The selective production of one structural isomer among many. Often used synonymously with ‘site selectivity’ in carbohydrate chemistry.

Kinetic control

The selectivity outcome of a reaction which is primarily determined by the rate of product formation.

Substrate control

Effectively the opposite of catalyst control. The selectivity of a reaction is defined by the information (perhaps chiral) inherent to the substrate and is not easily overridden.

Mesoscale inhomogeneity

A concept used to describe the formation of solute-containing clusters on the order of 100 nm and larger in the presence of solvent molecules.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Loh, C.C.J. Exploiting non-covalent interactions in selective carbohydrate synthesis. Nat Rev Chem 5, 792–815 (2021). https://doi.org/10.1038/s41570-021-00324-y

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41570-021-00324-y

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing