Synthesis 2023; 55(09): 1337-1354
DOI: 10.1055/a-1938-2293
special topic
Bürgenstock Special Section 2022 – Future Stars in Organic Chemistry

Recent Developments in Solid-Phase Glycan Synthesis

a   Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Am Mühlenberg 1, 14476 Potsdam, Germany
b   Department of Chemistry and Biochemistry, Freie Universität Berlin, Arnimallee 22, 14195 Berlin, Germany
,
a   Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Am Mühlenberg 1, 14476 Potsdam, Germany
› Author Affiliations
This work was supported by the Bundesministerium für Bildung und Forschung (German Federal Ministry of Education and Research) (Grant no. 13XP5114), the Max-Planck-Gesellschaft (Max Plank Society­), and the MPG-FhG Cooperation Project GLyco3Dsplay. J.Y.H acknowledges the International Max Planck Research School on Multiscale­ Bio-Systems for funding.


Abstract

Solid-phase glycan synthesis (SPGS) is a valuable approach to access broad collections of complex, well-defined oligo- and polysaccharides in short amounts of time. The target structure is assembled following iterative cycles of glycosylation and deprotection, often aided by automated machines. To expand the scope of SPGS, new solid supports, linkers, glycosylation and deprotection reactions, and functionalization strategies are constantly being developed. Here we discuss the state of the art of SPGS, with particular focus on the chemistry happening on solid-phase. We highlight recent achievements as well as challenges to be addressed to expand the scope of SPGS even further.

1 Introduction

2 Solid-Phase Glycan Synthesis

2.1 The Solid Support

2.2 The Linker

2.3 The Assembly Process

2.4 Post-Assembly Manipulations

2.5 The Analysis

2.6 Cleavage from the Solid Support

3 Conclusion and Outlook



Publication History

Received: 14 July 2022

Accepted after revision: 07 September 2022

Accepted Manuscript online:
07 September 2022

Article published online:
18 October 2022

© 2022. Thieme. All rights reserved

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Essentials of Glycobiology, 3rd ed. Varki A, Cummings RD, Esko JD, Stanley P, Hart G, Aebi M, Darvill AG, Kinoshita T, Packer NH, Prestegard JH, Schnaar RL, Seeberger PH. Cold Spring Harbor Laboratory Press; New York: 2017
  • 2 Fittolani G, Tyrikos-Ergas T, Vargová D, Chaube MA, Delbianco M. Beilstein J. Org. Chem. 2021; 17: 1981
  • 3 Krasnova L, Wong C.-H. J. Am. Chem. Soc. 2019; 141: 3735
  • 4 Marshall WS, Kaiser RJ. Curr. Opin. Chem. Biol. 2004; 8: 222
  • 5 Coin I, Beyermann M, Bienert M. Nat. Protoc. 2007; 2: 3247
  • 6 Jaradat DM. M. Amino Acids 2018; 50: 39
  • 7 Catani M, De Luca C, Medeiros Garcia Alcântara J, Manfredini N, Perrone D, Marchesi E, Weldon R, Müller-Späth T, Cavazzini A, Morbidelli M, Sponchioni M. Biotechnol. J. 2020; 15: 1900226
  • 8 Joseph AA, Pardo-Vargas A, Seeberger PH. J. Am. Chem. Soc. 2020; 142: 8561
  • 9 Guberman M, Seeberger PH. J. Am. Chem. Soc. 2019; 141: 5581
  • 10 Seeberger PH, Haase W.-C. Chem. Rev. 2000; 100: 4349
  • 11 Bennett CS. Org. Biomol. Chem. 2014; 12: 1686
  • 12 Seeberger PH. Acc. Chem. Res. 2015; 48: 1450
  • 13 Panza M, Pistorio SG, Stine KJ, Demchenko AV. Chem. Rev. 2018; 118: 8105
  • 14 Pardo-Vargas A, Delbianco M, Seeberger PH. Curr. Opin. Chem. Biol. 2018; 46: 48
  • 15 Hahm HS, Schlegel MK, Hurevich M, Eller S, Schuhmacher F, Hofmann J, Pagel K, Seeberger PH. Proc. Natl. Acad. Sci. 2017; 114: E3385
  • 16 Panza M, Stine KJ, Demchenko AV. Chem. Commun. 2020; 56: 1333
  • 17 Danglad-Flores J, Leichnitz S, Sletten ET, Abragam Joseph A, Bienert K, Le Mai Hoang K, Seeberger PH. J. Am. Chem. Soc. 2021; 143: 8893
  • 18 Sletten ET, Danglad-Flores J, Nuño M, Guthrie D, Seeberger PH. Org. Lett. 2020; 22: 4213
  • 19 Zhang J, Chen C, Gadi MR, Gibbons C, Guo Y, Cao X, Edmunds G, Wang S, Liu D, Yu J, Wen L, Wang PG. Angew. Chem. Int. Ed. 2018; 57: 16638
  • 20 Lepenies B, Yin J, Seeberger PH. Curr. Opin. Chem. Biol. 2010; 14: 404
  • 21 Yu Y, Tyrikos-Ergas T, Zhu Y, Fittolani G, Bordoni V, Singhal A, Fair RJ, Grafmüller A, Seeberger PH, Delbianco M. Angew. Chem. Int. Ed. 2019; 58: 13127
  • 22 Merrifield RB. J. Am. Chem. Soc. 1963; 85: 2149
  • 23 Vaino AR, Janda KD. J. Comb. Chem. 2000; 2: 579
  • 24 Moss JA. Curr. Protoc. Protein Sci. 2005; 40: 1
  • 25 Toy PH, Janda KD. Tetrahedron Lett. 1999; 40: 6329
  • 26 Kadonaga Y, Wang N, Fujimoto Y, Fukase K. Chem. Lett. 2014; 43: 1461
  • 27 Panza M, Neupane D, Stine KJ, Demchenko AV. Chem. Commun. 2020; 56: 10568
  • 28 Zhang J, Liu D, Saikam V, Gadi MR, Gibbons C, Fu X, Song H, Yu J, Kondengaden SM, Wang PG, Wen L. Angew. Chem. Int. Ed. 2020; 59: 19825
  • 29 Ramadan S, Su G, Baryal K, Hsieh-Wilson LC, Liu J, Huang X. Org. Chem. Front. 2022; 9: 2910
  • 30 Huang Q, Long Q, Zheng B. In Organic Synthesis on Solid Phase . Zaragoza Dorwald F. Wiley-VCH; Weinheim: 2004: 39
  • 31 Wu X, Grathwohl M, Schmidt RR. Angew. Chem. Int. Ed. 2002; 41: 4489
  • 32 Kröck L, Esposito D, Castagner B, Wang C.-C, Bindschädler P, Seeberger PH. Chem. Sci. 2012; 3: 1617
  • 33 Czechura P, Guedes N, Kopitzki S, Vazquez N, Martin-Lomas M, Reichardt NC. Chem. Commun. 2011; 47: 2390
  • 34 Ekholm FS, Leino R. Acyl Migrations in Carbohydrate Chemistry. In Protecting Groups: Strategies and Applications in Carbohydrate Chemistry. Vidal S. Wiley-VCH; Weinheim: 2018: 227
  • 35 Andrade RB, Plante OJ, Melean LG, Seeberger PH. Org. Lett. 1999; 1: 1811
  • 36 Timmer MS. M, Codée JD. C, Overkleeft HS, van Boom JH, van der Marel GA. Synlett 2004; 2155
  • 37 Klán P, Šolomek T, Bochet CG, Blanc A, Givens R, Rubina M, Popik V, Kostikov A, Wirz J. Chem. Rev. 2013; 113: 119
  • 38 Le Mai Hoang K, Pardo-Vargas A, Zhu Y, Yu Y, Loria M, Delbianco M, Seeberger PH. J. Am. Chem. Soc. 2019; 141: 9079
  • 39 Eller S, Collot M, Yin J, Hahm HS, Seeberger PH. Angew. Chem. Int. Ed. 2013; 52: 5858
  • 40 Weishaupt MW, Matthies S, Hurevich M, Pereira CL, Hahm HS, Seeberger PH. Beilstein J. Org. Chem. 2016; 12: 1440
  • 41 Schumann B, Hahm HS, Parameswarappa SG, Reppe K, Wahlbrink A, Govindan S, Kaplonek P, Pirofski L.-A, Witzenrath M, Anish C, Pereira CL, Seeberger PH. Sci. Transl. Med. 2017; 9: eaaf5347
  • 42 Geissner A, Seeberger PH. Annu. Rev. Anal. Chem. 2016; 9: 223
  • 43 Dallabernardina P, Ruprecht C, Smith PJ, Hahn MG, Urbanowicz BR, Pfrengle F. Org. Biomol. Chem. 2017; 15: 9996
  • 44 Geissner A, Reinhardt A, Rademacher C, Johannssen T, Monteiro J, Lepenies B, Thépaut M, Fieschi F, Mrázková J, Wimmerova M, Schuhmacher F, Götze S, Grünstein D, Guo X, Hahm HS, Kandasamy J, Leonori D, Martin CE, Parameswarappa SG, Pasari S, Schlegel MK, Tanaka H, Xiao G, Yang Y, Pereira CL, Anish C, Seeberger PH. Proc. Natl. Acad. Sci. U.S.A. 2019; 116: 1958
  • 45 Zhu Y, Delbianco M, Seeberger PH. J. Am. Chem. Soc. 2021; 143: 9758
  • 46 Tyrikos-Ergas T, Bordoni V, Fittolani G, Chaube MA, Grafmüller A, Seeberger PH, Delbianco M. Chem. Eur. J. 2021; 27: 2321
  • 47 Geert Volbeda A, van Mechelen J, Meeuwenoord N, Overkleeft HS, van der Marel GA, Codée JD. C. J. Org. Chem. 2017; 82: 12992
  • 48 Crich D. Acc. Chem. Res. 2010; 43: 1144
  • 49 Hettikankanamalage AA, Lassfolk R, Ekholm FS, Leino R, Crich D. Chem. Rev. 2020; 120: 7104
  • 50 Naresh K, Schumacher F, Hahm HS, Seeberger PH. Chem. Commun. 2017; 53: 9085
  • 51 Sabbavarapu NM, Seeberger PH. J. Org. Chem. 2021; 86: 7280
  • 52 Delbianco M, Kononov A, Poveda A, Yu Y, Diercks T, Jiménez-Barbero J, Seeberger PH. J. Am. Chem. Soc. 2018; 140: 5421
  • 53 Fittolani G, Shanina E, Guberman M, Seeberger PH, Rademacher C, Delbianco M. Angew. Chem. Int. Ed. 2021; 60: 13302
  • 54 Tyrikos-Ergas T, Sletten ET, Huang J.-Y, Seeberger PH, Delbianco M. Chem. Sci. 2022; 13: 2115
  • 55 Enugala R, Carvalho LC. R, Dias Pires MJ, Marques MM. B. Chem. Asian J. 2012; 7: 2482
  • 56 Poveda A, Fittolani G, Seeberger PH, Delbianco M, Jiménez-Barbero J. Front. Mol. Biosci. 2021; 8: 1
  • 57 Hayashi T, Kehr G, Bergander K, Gilmour R. Angew. Chem. Int. Ed. 2019; 58: 3814
  • 58 DeYong AE, Rudich ML, Pohl NL. B. Synthesis of Carbohydrate Building Blocks for Automated Oligosaccharide Construction. In Comprehensive Glycoscience, Vol. 2. Vidal S. Elsevier; Amsterdam: 2021: 637
  • 59 Marchesi A, Parmeggiani F, Louçano J, Mattey AP, Huang K, Gupta T, Salwiczek M, Flitsch SL. Angew. Chem. Int. Ed. 2020; 132: 22642
  • 60 Xu F.-F, Pereira CL, Seeberger PH. Beilstein J. Org. Chem. 2017; 13: 1994
  • 61 Guberman M, Bräutigam M, Seeberger PH. Chem. Sci. 2019; 10: 5634
  • 62 Hsu M.-Y, Lam S, Wu C.-H, Lin M.-H, Lin S.-C, Wang C.-C. Molecules 2020; 25: 1103
  • 63 Mishra B, Neralkar M, Hotha S. Angew. Chem. Int. Ed. 2016; 55: 7786
  • 64 Sutar Y, Vangala M, Hotha S. Chem. Commun. 2022; 58: 641
  • 65 Nigudkar SS, Stine KJ, Demchenko AV. J. Am. Chem. Soc. 2014; 136: 921
  • 66 Zhuo M.-H, Wilbur DJ, Kwan EE, Bennett CS. J. Am. Chem. Soc. 2019; 141: 16743
  • 67 Frihed TG, Bols M, Pedersen CM. Chem. Rev. 2015; 115: 4963
  • 68 Andreana PR, Crich D. ACS Cent. Sci. 2021; 7: 1454
  • 69 Tuck OT, Sletten ET, Danglad-Flores J, Seeberger PH. Angew. Chem. Int. Ed. 2022; 61: e202115433
  • 70 Nicolardi S, Joseph AA, Zhu Q, Shen Z, Pardo-Vargas A, Chiodo F, Molinaro A, Silipo A, Van Der Burgt YE. M, Yu B, Seeberger PH, Wuhrer M. Anal. Chem. 2021; 93: 4666
  • 71 Komarova BS, Tsvetkov YE, Nifantiev NE. Chem. Rec. 2016; 16: 488
  • 72 Satoh H, Hansen HS, Manabe S, van Gunsteren WF, Hünenberger PH. J. Chem. Theory Comput. 2010; 6: 1783
  • 73 Boons G.-J, Bowers S, Coe DM. Tetrahedron Lett. 1997; 38: 3773
  • 74 Boltje TJ, Kim JH, Park J, Boons GJ. Nat. Chem. 2010; 2: 552
  • 75 Park Y, Harper KC, Kuhl N, Kwan EE, Liu RY, Jacobsen EN. Science 2017; 355: 162
  • 76 Walvoort MT. C, van den Elst H, Plante OJ, Kröck L, Seeberger PH, Overkleeft HS, van der Marel GA, Codée JD. C. Angew. Chem. Int. Ed. 2012; 51: 4393
  • 77 Codée JD. C, van den Bos LJ, de Jong A.-R, Dinkelaar J, Lodder G, Overkleeft HS, van der Marel GA. J. Org. Chem. 2009; 74: 38
  • 78 Hahm HS, Hurevich M, Seeberger PH. Nat. Commun. 2016; 7: 12482
  • 79 Newcomb WS, Deegan TL, Miller W, Porco JA. Biotechnol. Bioeng. 1998; 61: 55
  • 80 Schmidt D, Schuhmacher F, Geissner A, Seeberger PH, Pfrengle F. Chem. Eur. J. 2015; 21: 5709
  • 81 Senf D, Ruprecht C, de Kruijff GH. M, Simonetti SO, Schuhmacher F, Seeberger PH, Pfrengle F. Chem. Eur. J. 2017; 23: 3197
  • 82 Takaku H, Kamaike K. Chem. Lett. 1982; 11: 189
  • 83 Yu Y, Kononov A, Delbianco M, Seeberger PH. Chem. Eur. J. 2018; 24: 6075
  • 84 Schuster M, Wang P, Paulson JC, Wong C.-H. J. Am. Chem. Soc. 1994; 116: 1135
  • 85 Gray CJ, Weissenborn MJ, Eyers CE, Flitsch SL. Chem. Soc. Rev. 2013; 42: 6378
  • 86 Yu Y, Gim S, Kim D, Arnon ZA, Gazit E, Seeberger PH, Delbianco M. J. Am. Chem. Soc. 2019; 141: 4833
  • 87 Kanie O, Grotenbreg G, Wong CH. Angew. Chem. Int. Ed. 2000; 39: 4545
  • 88 Tanaka H, Ishida T, Matoba N, Tsukamoto H, Yamada H, Takahashi T. Angew. Chem. Int. Ed. 2006; 45: 6349
  • 89 Cavedon C, Sletten ET, Madani A, Niemeyer O, Seeberger PH, Pieber B. Org. Lett. 2021; 23: 514
  • 90 Zhu Y, Tyrikos-Ergas T, Schiefelbein K, Grafmüller A, Seeberger PH, Delbianco M. Org. Biomol. Chem. 2020; 18: 1349
  • 91 Hahm HS, Broecker F, Kawasaki F, Mietzsch M, Heilbronn R, Fukuda M, Seeberger PH. Chem 2017; 2: 114
  • 92 Sletten ET, Danglad-Flores J, Leichnitz S, Abragam Joseph A, Seeberger PH. Carbohydr. Res. 2022; 511: 108489
  • 93 Fair RJ, Hahm HS, Seeberger PH. Chem. Commun. 2015; 51: 6183
  • 94 Seeberger PH, Beebe X, Sukenick GD, Pochapsky S, Danishefsky SJ. Angew. Chem. Int. Ed. 1997; 36: 491
  • 95 Kanemitsu T, Kanie O, Wong C.-H. Angew. Chem. Int. Ed. 1998; 37: 3415
  • 96 Mogemark M, Elofsson M, Kihlberg J. Org. Lett. 2001; 3: 1463
  • 97 Attardi ME, Taddei M. Tetrahedron Lett. 2000; 41: 7395
  • 98 Manabe S, Ito Y. J. Am. Chem. Soc. 2002; 124: 12638
  • 99 Roussel F, Knerr L, Grathwohl M, Schmidt RR. Org. Lett. 2000; 2: 3043
  • 100 Routenberg Love K, Seeberger PH. Angew. Chem. Int. Ed. 2004; 43: 602
  • 101 Ko K.-S, Park G, Yu Y, Pohl NL. Org. Lett. 2008; 10: 5381
  • 102 Ajayaghosh A, Rajasekharan Pillai VN. Tetrahedron 1988; 44: 6661
  • 103 Bakhatan Y, Alshanski I, Grunhaus D, Hurevich M. Org. Biomol. Chem. 2020; 18: 4183
  • 104 Teschers CS, Gilmour R. Org. Process Res. Dev. 2020; 24: 2234
  • 105 Pardo-Vargas A, Bharate P, Delbianco M, Seeberger PH. Beilstein J. Org. Chem. 2019; 15: 2936
  • 106 Louçano J, Both P, Marchesi A, del Bino L, Adamo R, Flitsch S, Salwiczek M. RSC Adv. 2020; 10: 23668
  • 107 Anggara K, Zhu Y, Delbianco M, Rauschenbach S, Abb S, Seeberger PH, Kern K. J. Am. Chem. Soc. 2020; 142: 21420
  • 108 Wu X, Delbianco M, Anggara K, Michnowicz T, Pardo-Vargas A, Bharate P, Sen S, Pristl M, Rauschenbach S, Schlickum U, Abb S, Seeberger PH, Kern K. Nature 2020; 582: 375
  • 109 Anggara K, Zhu Y, Fittolani G, Yu Y, Tyrikos-Ergas T, Delbianco M, Rauschenbach S, Abb S, Seeberger PH, Kern K. Proc. Natl. Acad. Sci. U.S.A. 2021; 118: e2102168118
  • 110 Fittolani G, Vargová D, Seeberger PH, Ogawa Y, Delbianco M. J. Am. Chem. Soc. 2022; 144: 12469
  • 111 Amblard M, Fehrentz JA, Martinez J, Subra G. Mol. Biotechnol. 2006; 33: 239
  • 112 Sletten ET, Nuño M, Guthrie D, Seeberger PH. Chem. Commun. 2019; 55: 14598