Correction to “Efficient Synthesis of Muramic and Glucuronic Acid Glycodendrimers as Dengue Virus Antagonists”

Chem. Eur. J. 2020, 26, e201903788

10.1002/chem.201903788

The journal has been made aware of an error in the experimental protocol for the synthesis of compounds 17, 21, and 25. At the time, we inadvertently followed a previously described procedure published in Chem. Eur. J. in 2017, which was optimized for sugars lacking ester groups. Consequently, the synthetic methodology described in the experimental section and the results and discussion section, of our article was incorrect. Nevertheless, the click chemistry reaction was performed on the fully deprotected sugar.

To ensure accuracy and rectify the errors, the authors have repeated the synthesis of these compounds, and the corrected details are provided below. The authors sincerely apologize for these mistakes, which do not impact the validity of any other data or conclusions in the original manuscript.

The corrected structures for Scheme 2 and Scheme 3, along with the revised text in the Results and Discussion and Experimental sections for compounds 17, 21, and 25, are provided below. Additionally, the corrected scheme for compounds 10a–e and the updated NMR spectra for compounds 17, 21, and 25, recorded in D₂O to minimize signal overlap from CD₃OD, are included in the Supporting Information.

Changes in the Results and Discussion section:

Scheme 2, in compound 9b, R = CH₂-CH₂-CH_3, and compounds 10 (10a–d) should be presented in their ester form. Scheme 3 has been revised to correctly describe the synthesis of the glucuronic acid-based glycodendrimers 17, 21, and 25.

The corrected procedure for the synthesis of compounds 17 and 25 involves the Cu-catalyzed cycloaddition reaction between fully deprotected β-glucuronic acid azide (10e) and the corresponding dendritic cores (11 and 13). Compound 10e was obtained by treating 10d with 0.2 M NaOH aqueous solution (4.4 equiv.) and the reaction was quenched by adding Amberlite resin until pH 3 was reached, affording 10e in quantitative yields.

The synthesis of the glucuronic acid glycodendrimer 21 was performed via a Cu-catalyzed cycloaddition reaction between the fully protected β-glucuronic acid azide (9d) and the dendritic core (12). Deprotection of the glucuronic acid derivative 20 was achieved by treatment with NaOMe/MeOH and NaOH, followed by neutralization with Amberlite resin, affording the final compound (21) in quantitative yield.

Changes in the Experimental Section:

Synthesis of Compound 17 and 25

CuSO₄·5H₂O (0.15 equiv./alkyne) and TBTA (0.3 equiv./alkyne) were dissolved in a DMSO:H₂O (5:1) mixture, while sodium ascorbate (0.35 equiv./alkyne) was dissolved in water. Both solutions were added to a previously prepared solution of compound 10e (1.5 equiv./alkyne) and the corresponding divalent (11) or tetravalent (13) core in a DMSO:H₂O (5:1) mixture. The reaction mixture was stirred at 60 °C under microwave irradiation for 90 minutes. Copper was removed using Quadrasil MP resin, and the products were purified by size-exclusion chromatography on Sephadex LH-20 using MeOH:H₂O as eluent (90:10 for 17, 80:20 for 25). Fractions containing the glycodendrimers were evaporated under vacuum and washed with CH₂Cl₂ to remove residual TBTA, affording compounds 17 (51 mg, 40% yield) and 25 (65 mg, 73% yield) as white solids.

17: ¹H-NMR (500 MHz, D₂O) δ (ppm): 8.1 (s br, 2H, H-11), 7.22 (s, 2H, H-2 and H-6), 6.84 (s, 1H, H-4), 5.22 (s br, 4H, H-9), 4.55 (s br, 4H, H-12), 4.30 (d, J = 7.9 Hz, 2H, H-1′), 3.89 (s, 3H, H-8), 3.80–3.77 (m, 2H, H-14a), 3.73 (t, J = 8.9 Hz, 2H, H-4′), 3.54–3.44 (m, 6H, H-2′, H-14b, H-5′), 3.30 (t, J = 8.9 Hz, 2H, H-3′), 2.18 (m, 4H, H-13).

¹³C-NMR (125 MHz, D₂O) δ (ppm): 174.2 (C-6′), 168.2 (C-7), 158.5 (C-3 and C-5), 142.8 (C-10), 131.6 (C-1), 125.8 (C-11), 109.5 (C-2 and C-6), 108.3 (C-4), 102.2 (C-1′), 75.4 (C-3′ and C-5′), 72.7 (C-2′), 71.6 (C-4′), 66.2 (C-14), 61.6 (C-9), 52.8 (C-8), 47.03 (C-12), 29.4 (C-13).

25: ¹H-NMR (500 MHz, D₂O) δ (ppm): 7.83 (s br, 4H, H-25), 6.78 (s, 2H, H-2 and H-6), 6.37 (s, 7H, H-4, H-11, H-15, H-18, H-19, H-22, and H-24), 4.51 (s br, 4H, H-9 and H-16), 4.36–4.31 (m, 12H, H-26 and H-1′), 3.80–3.68 (m, 7H, H-8 and H-5′), 3.62–3.59 (m, 4H, H-4′ or 3′), 3.47 (m, 12H, H-28 and H-2′), 3.31 (t, J = 8.4 Hz, 4H, H-3′ or 4′), 2.10–1.92 (m, 8H, H-27) (H-23 are overlapped with H₂O signal)

¹³C-NMR (125 MHz, D₂O) δ (ppm): 170.5 (C-6′), 167.0 (C-7), 158.9 (C-12, C-14, C-19, and C-20), 158.8 (C-3 and C-5), 143.0 (C-24), 139.0 (C-10 and C-17), 131.2 (C-1), 124.9 (C-25), 107.9 (C-2 and C-6), 106.5 (C-11, C-15, C-18, and C-22), 102.2 (C-1′), 100.8 (C-13 and C-20), 75.3 (C-3′), 72.8 (C-5′ and C-2′), 71.5 (C-4′), 69.0 (C-9 and C-16), 66.3 (C-28), 60.9 (C-23), 52.5 (C-8), 47.1 (C-26), 29.5 (C-27).

Deprotection of Compound 20

The peracetylated derivative 20 was dissolved in 2 mL of anhydrous MeOH. The solution was sequentially treated with 0.5 N NaOMe/MeOH (9 equiv.) and 0.2 M NaOH aq. (4.5 equiv.). The reaction was quenched by adding Amberlite resin until pH 3, filtered, and concentrated under vacuum, affording glycodendrimer 21 as a white powder in quantitative yield.

21: ¹H-NMR (500 MHz, D₂O) δ (ppm): 7.96 (s br, 3H, H-9), 6.17 (s, 2H, H-2 and H-6), 5.99 (s, 1H, H-4), 5.03 (s br, 6H, H-7), 4.42 (s br, 6H, H-10), 4.24 (d, J = 7.9 Hz, 3H, H-1′), 3.78 (d, J = 9.6 Hz, 3H, H-5′), 3.78–3.71 (m, 3H, H-12a), 3.50–3.44 (m, 9H, H-2′, H-4′, H-12b), 3.14 (m, 3H, H-3′), 2.05 (s br, 6H, H-11).

¹³C-NMR (125 MHz, D₂O) δ (ppm): 172.7 (C-6′), 159.2 (C-1, C-3, and C-5), 143.0 (C-8), 125.7 (C-9), 100.3 (C-1′), 95.8 (C-2, C-4, and C-6), 75.2 (C-3′), 74.7 (C-5′), 72.7 (C-2′), 71.3 (C-4′), 66.3 (C-12), 61.3 (C-7), 46.9 (C-10), 29.3 (C-11).

The NMR characterization of compound 20 corresponds to that of compound 24, and vice versa; the characterization of compound 24 corresponds to that of compound 20.

A revised Supporting Information that includes these changes has been provided.

We apologize for these errors and appreciate the opportunity to correct them.