A Synthetic Approach for Hepta-Branched β-Cyclodextrins Bearing Heterogeneous Carbohydrate Residues at Their Primary Side via a One-Pot Process with a Simultaneous Click Chemistry Reaction

Abstract

In this study, a synthetic approach is reported for generating hepta-branched β-cyclodextrins (CDs) bearing heterogeneous carbohydrate residues at their primary side via a one-pot process with a simultaneous click chemistry reaction. The reactions were performed by reacting two or three different species of 2-propynylated glycosides with a hepta-azide functional β-CD at various reaction molar ratios. 2-Propynylated glycosides acted as heterogeneous carbohydrate sources embedded into a hepta-azide functional β-CD. The simultaneous click chemistry reactions generated several desired β-CD derivatives with varying densities of the heterogeneous carbohydrates in a one-pot process. The article describes the effects of the combination of 2-propynylated glycosides and the reaction molar ratios in the click chemistry reactions.

Key words

cyclodextrin - click chemistry reaction - carbohydrate-branched cyclodextrin - heteroglycoconjugate - heterogeneous carbohydrate - simultaneous reaction

Publikationsverlauf

Eingereicht: 19. Oktober 2023

Angenommen nach Revision: 01. November 2023

Accepted Manuscript online:
01. November 2023

Artikel online veröffentlicht:
06. Dezember 2023

• References

• 1 Yu Z, Yu Y, Gao B, Wang D, Sun H, Feng Y, Ma Z, Xie X. Glycoconjugate J. 2023; 40: 355
• 2 Cao X, Wang S, Gadi MR, Liu D, Wang PG, Wan X.-F, Zhang J, Chen X, Pepi LE, Azadih P, Li L. Chem. Sci. 2022; 13: 7644
• 3 Madsen TD, Hansen LH, Hintze J, Ye Z, Jebari S, Andersen DB, Joshi HJ, Ju T, Goetze JP, Martin C, Rosenkilde MM, Holst JJ, Kuhre RE, Goth CK, Vakhrushev SY, Schjoldager KT. Nat. Commun. 2020; 11: 4033
• 4 Reily C, Stewart TJ, Renfrow MB, Novak J. Nat. Rev. Nephrol. 2019; 15: 346
• 5 Varki A. Glycobiology 2017; 27: 3
• 6 Martínez-Bailén M, Rojo J, Ramos-Soriano J. Chem. Soc. Rev. 2023; 52: 536
• 7 Kim Y, Hyun JY, Shin I. Chem. Soc. Rev. 2021; 50: 10567
• 8 Pramudya I, Chung H. Biomater. Sci. 2019; 7: 4848
• 9 Wilkins LE, Badi N, Prez FD, Gibson MI. ACS Macro Lett. 2018; 7: 1498
• 10 Wang X, Wang M, Wang C, Deng W, Liu M. Polym. Chem. 2021; 12: 4722
• 11 Wilkins LE, Badi N, Prez FD, Gibson MI, Wilkins LE, Badi N, Prez FD, Gibson MI. ACS Macro Lett. 2018; 7: 1498
• 12 Sletten ET, Loka RS, Yu F, Nguyen HM. Biomacromolecules 2017; 18: 3387
• 13 Loka RS, McConnell MS, Nguyen HM. Biomacromolecules 2015; 16: 4013
• 14 Smirnov I, Sibgatullina R, Urano S, Tahara T, Ahmadi P, Watanabe Y, Pradipta AR, Kurbangalieva A, Tanaka K. Small 2020; 16: 2004831
• 15 González-Cuesta M, Mellet CO, Fernández JM. G. Chem. Commun. 2020; 56: 5207
• 16 Flos MA, Moreno MI. G, Mellet CO, Fernández JM. G, Nierengarten J.-F, Vincent SP. Chem. Eur. J. 2016; 22: 11450
• 17 Jansook P, Ogawa N, Loftsson T. Int. J. Pharm. 2018; 535: 272
• 18 Conceicao J, Adeoye O, Cabral-Marques HM, Lobo JM. S. Curr. Pharm. Des. 2018; 24: 1405
• 19 Titov DV, Gening ML, Tsvetkov YE, Nifantiev NE. J. Org. Chem. 2013; 39: 451
• 20 Yamanoi T, Oda Y, Katsuraya K, Inazu T, Hattori K. Bioorg. Med. Chem. 2016; 24: 635
• 21 Oda Y, Miura M, Hattori K, Yamanoi T. Chem. Pharm. Bull. 2009; 57: 74
• 22 Oda Y, Yanagisawa H, Maruyama M, Hattori K, Yamanoi T. Bioorg. Med. Chem. 2008; 16: 8830
• 23 Yamanoi T, Yoshida N, Oda Y, Akaike E, Tsutsumida M, Kobayashi N, Osumi K, Yamamoto K, Fujita K, Takahashi K, Hattori K. Bioorg. Med. Chem. Lett. 2005; 15: 1009
• 24 Grünstein D, Maglinao M, Kikkeri R, Collot M, Barylyuk K, Lepenies B, Kamena F, Zenobi R, Seeberger PH. J. Am. Chem. Soc. 2011; 133: 13957
• 25 González-Cuesta M, Goyard D, Nanba E, Higaki K, Fernández JM. G, Renaudet O, Mellet CO. Chem. Commun. 2019; 55: 12845
• 26 García-Moreno MI, Ortega-Caballero F, Rísquez-Cuadro R, Mellet CO, Fernández JM. G. Chem. Eur. J. 2017; 23: 6295
• 27 Gómez-García M, Benito JM, Gutiérrez-Gallego R, Maestre A, Mellet CO, Fernández JM. G, Jimenez-Blanco JL. Org. Biomol. Chem. 2010; 8: 1849
• 28 Gómez-García M, Benito JM, Butera AP, Mellet CO, Fernández JM. G, Jimenez-Blanco JL. J. Org. Chem. 2012; 77: 1273
• 29 Gómez-García M, Benito JM, Rodríguez-Lucena D, Yu J.-X, Chmurski K, Mellet CO, Gallego RG, Maestre A, Defaye J, Fernández JM. G. J. Am. Chem. Soc. 2005; 127: 7970
• 30 Cho JH, Schinazi RF. Chem. Rev. 2009; 109: 4207
• 31 Roy R, Das SK, Santoyo-Gonzalez F, Dam TK, Brewer CF. Chem. Eur. J. 2000; 6: 1757
• 32 Boger J, Corcoran R, Lehn J. Helv. Chim. Acta 1978; 61: 2190
• 33 Click Chemistry Reaction; Typical Procedure (Click Reaction (A))Sodium ascorbate (5.6 mg, 0.028 mmol) and copper sulfate (9.7 mg, 0.039 mmol) were added to a solution of 1 (137.8 mg, 0.29 mmol) and 2 (111.1 mg, 0.29 mmol) and 5 (71.0 mg, 0.037 mmol) in THF (3.5 mL)–H₂O (3.5 mL). After the reaction mixture was heated to 70 °C under microwave irradiation at 18 W for 40 min, and stirring for 20 min, the reaction was quenched by adding sat. NaCl aq. (3 mL). The mixture was extracted with EtOAc (three times), and the combined organic solvent was dried over anhydrous Na₂SO₄. The organic solvent was filtered and evaporated under reduced pressure. The crude product was purified by preparative silica-gel TLC (CH₂Cl₂/MeOH = 20:1) to afford a mixture of compounds 6–11 (164.5 mg, total yield of 90%).Click reaction (A): A mixture of 6–11 (containing regioisomers); ¹H NMR (CDCl₃): δ = 1.86–2.06 (Ac), 3.58 (CD-4), 4.05–5.68 (αArb-1,2,3,4,5,6, αGlcNAc-1,2,3,4,5,6, CD-1,2,3,5,6, OCH₂-triazole), 6.87–7.00 (Ph), 7.83–7.91 (CH₂CCHN); ¹³C NMR (CDCl₃): δ = 20.5–23.0 (Ac), 50.0 (CD-6), 51.5 (αGlcNAc-2), 60.3–70.4 (αArb-2,3,4,5,6, αGlcNAc-3,4,5,6, CD-2,3,4,5, OCH₂-triazole), 95.1 (αArb-1), 96.3–96.5 (αGlcNAc-1, CD-1), 115.5, 118.0 (Ph), 125.7 (CH₂CCH), 143.7 (CH₂ CCH), 150.5, 154.0 (Ph), 169.2-171.1 (C=O).Click reaction (B): A mixture of 12 (containing regioisomers); ¹H NMR (CDCl₃): δ = 2.03–2.08 (Ac), 3.56 (CD-4), 3.89–5.68 (αArb-1,2,3,4,5,6, βArb-1,2,3,4,5,6, CD-1,2,3,5,6, OCH₂-triazole), 6.84–7.00 (Ph), 7.77–7.79 (CH₂CCHN); ¹³C NMR (CDCl₃): δ = 20.5–20.6 (Ac), 50.0 (CD-6), 61.5-72.6 (αArb-2,3,4,5,6, βArb-2,3,4,5,6, CD-2,3,4,5, OCH₂-triazole), 95.0 (αArb-1), 96.2–96.7 (CD-1), 99.8 (βArb-1), 115.4–118.4 (Ph), 125.8 (CH₂CCH), 143.7 (CH₂ CCH), 150.5–151.2 (Ph), 169.2–170.5 (C=O).Click reaction (C): A mixture of 13–19 (containing regioisomers); ¹H NMR (CDCl₃): δ = 1.90–2.09 (Ac), 3.57–3.58 (CD-4), 4.04–5.68 (αArb-1,2,3,4,5,6, αMan-1,2,3,4,5,6, CD-1,2,3,5,6, OCH₂-triazole), 6.85–7.00 (Ph), 7.81–8.00 (CH₂CCHN); ¹³C NMR (CDCl₃): δ = 20.5–21.0 (Ac), 50.1 (CD-6), 60.3–70.0 (αArb-2,3,4,5,6, αMan-2,3,4,5,6, CD-2,3,4,5, OCH₂-triazole), 95.0 (αArb-1), 96.2–96.7 (CD-1), 96.8–97.0 (αMan-1), 115.4–118.0 (Ph), 125.7 (CH₂CCH), 143.3–143.7 (CH₂ CCH), 150.5–154.1 (Ph), 169.4–171.0 (C=O).Click reaction (D): A mixture of 20–24 (containing regioisomers); ¹H NMR (CDCl₃): δ = 1.77–1.97 (Ac), 3.47–3.48 (CD-4), 3.57–5.33 (βArb-1,2,3,4,5,6, αGlcNAc-1,2,3,4,5,6, CD-1,2,3,5,6, OCH₂-triazole), 6.29–6.84 (Ph), 7.62–7.78 (CH₂CCHN); ¹³C NMR (CDCl₃): δ = 20.9–23.1 (Ac), 50.0 (CD-6), 52.1 (αGlcNAc-2), 62.2–73.1 (αArb-2,3,4,5,6, αGlcNAc-3,4,5,6, CD-2,3,4,5, OCH₂-triazole), 96.0–97.0 (αGlcNAc-1, CD-1), 99.9 (βArb-1), 116.1, 119.1 (Ph), 126.6 (CH₂CCH), 144.3–144.5 (CH₂ CCH), 152.1, 155.0 (Ph), 170.2–172.0 (C=O).Click reaction (E); A mixture of 10, 11, 25 and 26 (containing regioisomers); ¹H NMR (CDCl₃): δ = 1.70–2.10 (Ac), 3.58 (CD-4), 3.95–5.68 (αArb-1,2,3,4,5,6, αGlcNAc-1,2,3,4,5,6, CD-1,2,3,5,6, OCH₂-triazole), 6.70–7.00 (Ph), 7.83–7.91 (CH₂CCHN); ¹³C NMR (CDCl₃): δ = 20.8–22.9 (Ac), 50.0 (CD-6), 51.7 (αGlcNAc-2), 61.0–70.9 (αArb-2,3,4,5,6, αGlcNAc-3,4,5,6, CD-2,3,4,5, OCH₂-triazole), 95.0 (αArb-1), 96.4–96.6 (αGlcNAc-1, CD-1), 115.5, 118.0 (Ph), 125.7 (CH₂CCH), 143.7 (CH₂ CCH), 150.5, 153.9 (Ph), 169.2-171.0 (C=O).Click reaction (F): A mixture of 27–31 (containing regioisomers); ¹H NMR (CDCl₃): δ = 1.85–2.54 (Ac), 3.59 (CD-4), 3.89–5.40 (βArb-1,2,3,4,5,6, αGlcNAc-1,2,3,4,5,6, αMan-1,2,3,4,5,6, CD-1,2,3,5,6, OCH₂-triazole), 6.70–7.32 (Ph), 7.83–7.84 (CH₂CCHN); ¹³C NMR (CDCl₃): δ = 20.5–22.9 (Ac), 50.0 (CD-6), 51.7 (αGlcNAc-2), 61.6–72.5 (βArb-2,3,4,5,6, αGlcNAc-3,4,5,6, αMan-2,3,4,5,6, CD-2,3,4,5, OCH₂-triazole), 96.0–97.0 (αGlcNAc-1, αMan-1, CD-1), 99.6 (βArb-1), 115.2, 118.2 (Ph), 125.7 (CH₂CCH), 143.7 (CH₂ CCH), 151.0, 154.0 (Ph), 169.0-170.8 (C=O).