Click Chemistry Approach for
the Synthesis of Water-Soluble Glycodendrimer with Triazole
as Building Unit

Perumal Rajakumar; Ramasamy Anandhan; Venkatesan Kalpana

doi:10.1055/s-0029-1217170

LETTER

Click Chemistry Approach for the Synthesis of Water-Soluble Glycodendrimer with Triazole as Building Unit

Perumal Rajakumar*, Ramasamy Anandhan, Venkatesan Kalpana
Department of Organic Chemistry, University of Madras, Guindy Campus, Chennai 600025, India
Fax: +91(44)22300488; e-Mail: perumalrajakumar@hotmail.com;

Abstract

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Abstract

A new family of chiral glycodendrimers scaffolds containing di-, tetra- and octavalent glucose residues as peripheral unit and with 1,2,3-triazole as building unit has been synthesized through Cu(I)-catalyzed click chemistry by convergent approach.

Key words

click chemistry - glycodendrimers - chiral (S)-BINOL - alkynes - azide - 1,2,3-triazole

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Referenzen

References and Notes

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17

General Procedure for the Cu-Catalyzed Huisgen ‘Click Reaction’: Acetylenic derivative (1.0 mmol) was mixed with acetylated carbohydrate azide (2.1 mmol, 2.1 equiv) in t-BuOH and H₂O mixture (1:1, 8 mL) solution. Sodium ascorbate (0.4 mmol, 0.4 equiv) was added as a solid, followed by the addition of CuSO₄ (0.2 mmol, 0.2 equiv). The reaction was stirred overnight at r.t. The solvent was evaporated under reduced pressure and the crude product was dissolved in EtOAc (100 mL), washed with NH₄Cl solution (50 mL), brine solution (50 mL) and H₂O (50 mL) and then dried over Na₂SO₄ and concentrated on a rotary evaporator. The residue was purified by column chromatog-raphy (SiO₂) with hexane-EtOAc as eluent to give the corresponding triazole compound.

18

General Procedure for the Conversion of Dendritic Chlorides to Azides: Dendritic chloride (1.0 mmol) was dissolved in acetone and H₂O (4:1, 8 mL). NaN₃ (1.5 mmol, 1.5 equiv) was added, and the mixture was heated at 60 ˚C for 3 h. The reaction mixture was cooled to r.t., acetone was evaporated and the reaction mixture was diluted with H₂O (100 mL), and extracted with EtOAc (2 × 100 mL). The organic layer was washed with sat. NaCl (50 mL), dried over Na₂SO₄, and evaporated to give the dendritic azide.

19

First-Generation Dendritic Azide 11: white solid; yield: 99%; R _f 0.6 (EtOAc-hexane, 1:1); mp 133 ˚C. ^¹H NMR (300 MHz, CDCl₃): δ = 1.78, 1.96, 2.00 (3 × s, 24 H), 3.92-3.97 (m, 2 H), 4.04-4.11 (m, 2 H), 4.21-4.26 (m, 4 H), 5.13 (s, 4 H), 5.18-5.21 (m, 2 H), 5.32-5.43 (m, 4 H), 5.84 (d, J = 2.7 Hz, 2 H), 6.50 (d, J = 2.1 Hz, 2 H), 6.57 (d, J = 2.1 Hz, 1 H), 7.86 (s, 2 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 19.1, 19.5, 19.5, 19.6, 53.6, 60.6, 60.9, 66.8, 69.4, 71.7, 74.2, 84.8, 100.6, 106.8, 120.3, 137.0, 143.6, 158.6, 167.9, 168.4, 168.9, 169.5. MS (FAB): m/z = 987 [M⁺]. Anal. Calcd for C₄₁H₄₉N₉O₂₀: C, 49.85; H, 5.00; N, 12.76. Found: C, 49.81; H, 4.96; N, 12.51.

20

Second-Generation Dendritic Azide 13: white solid; yield: 99%; R _f 0.72 (EtOAc-hexane, 7:3); mp 159 ˚C. ^¹H NMR (300 MHz, CDCl₃): δ = 1.82, 2.02, 2.05, 2.07 (4 × s, 48 H), 4.02-4.05 (m, 4 H), 4.11-4.17 (m, 4 H), 4.24 (d, J = 4.8 Hz, 2 H), 4.27-4.32 (m, 4 H), 5.14 (s, 8 H), 5.17 (s, 4 H), 5.27 (t, J = 9.6 Hz, 4 H), 5.39-5.50 (m, 12 H), 5.93 (d, J = 8.7 Hz, 4 H), 6.51 (s, 4 H), 6.59 (s, 2 H), 6.60 (s, 1 H), 6.64 (s, 2 H), 7.63 (s, 2 H), 7.96 (s, 4 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 20.1, 20.5, 20.5, 20.6, 54.0, 54.6, 61.6, 61.8, 62.1, 67.7, 70.4, 72.6, 75.1, 85.8, 101.7, 107.9,107.7, 107.8, 121.6, 123.0, 137.0, 144.2, 144.3, 159.4, 159.7, 168.9, 169.4, 169.9, 170.5. MS (FAB): m/z = 2217 [M⁺]. Anal. Calcd for C₉₅H₁₀₉N₂₁O₄₂: C, 51.46; H, 4.95; N, 13.27. Found: C, 51.41; H, 4.90; N, 13.14.

21

General Procedure for the De-O-acetylation (Zemplen Reaction): Acetylated dendrimers (1.0 mmol) was dissolved in a mixture of anhyd MeOH-anhyd THF-anhyd CH₂Cl₂ (16 mL, 6:1:1) and to this mixture was added a solution of sodium methoxide (1 M MeOH) until pH 9-10 was reached. The reaction was stirred at r.t. for 48 h. At the end, H₂O was added for entire solubilization of desired compound and the solution was neutralized by addition of ion-exchange resin (Amberlite IR 120 H⁺) until pH 6-7 was attained. The solution was filtered and the solvent was removed in vacuo with rotary evaporator. The residue was then lyophilized to yield the fully deprotected glycodenrimer in a ca. 99% yield.

22

Glycodendrimer 2: white solid; yield: 95%; [α]_D ^²5 +44.5
(c = 1, DMSO). IR (KBr): 3404, 1372, 1230, 1042, 826 cm^-¹. ^¹H NMR (300 MHz, CDCl₃): δ = 3.21 (d, J = 8.4 Hz, 4 H), 3.55-3.66 (m, 8 H), 5.18 (q, J = 3.6 Hz, 4 H), 5.43 (d, J = 9.0 Hz, 2 H), 6.88 (d, J = 8.4 Hz, 2 H), 7.22 (t, J = 7.4 Hz, 2 H), 7.33 (t, J = 7.5 Hz, 2 H), 7.75-7.78 (m, 4 H), 7.94 (d, J = 9.0 Hz, 2 H), 8.06 (d, J = 9.0 Hz, 2 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 60.4, 62.2, 72.0, 76.4, 79.4, 87.2, 115.8, 119.3, 123.0, 123.9, 124.4, 126.5, 128.9, 129.5, 133.2, 143.2, 143.2, 153.4. MS (FAB): m/z = 772 [M⁺]. Anal. Calcd for C₃₈H₄₀N₆O₁₂: C, 59.06; H, 5.22; N, 10.88. Found: C, 59.03; H, 5.20; N, 10.87.

23

Glycodendrimer 4: white solid; yield: 92%; [α]_D ^²5 +15.5
(c = 1, DMSO). IR (KBr): 3426, 1595, 1412, 1046, 834 cm^-¹. ^¹H NMR (300 MHz, CDCl₃): δ = 3.00 (s, 8 H), 3.43-3.56 (m, 8 H), 4.85-4.94 (m, 12 H), 5.14 (s, 8 H), 5.31 (d, J = 9.0 Hz, 4 H), 5.54 (s, 4 H), 6.26 (s, 4 H), 6.53 (s, 2 H), 6.60 (d, J = 8.4 Hz, 2 H), 7.90 (t, J = 7.5 Hz, 2 H), 7.04 (t, J = 7.5 Hz, 2 H), 7.34 (s, 2 H), 7.45 (d, J = 9.0 Hz, 2 H), 7.65 (d, J = 9.0 Hz, 2 H), 7.76 (d, J = 9.0 Hz, 2 H), 8.20 (s, 4 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 52.7, 60.5, 60.8, 62.3, 69.2, 72.0, 76.6, 79.4, 87.4, 100.8, 107.1, 115.8, 119.3, 123.8, 124.0, 124.3, 126.3, 128.0, 128.9, 129.4, 133.1, 137.7, 142.4, 143.5, 153.2, 159.3. MS (MALDI-TOF): m/z = 1665 [M⁺]. Anal. Calcd for C₇₆H₈₄N₁₈O₂₆: C, 54.80; H, 5.08; N, 15.14. Found: C, 54.79; H, 5.08; N, 15.11.

24

Glycodendrimer 6: white solid; yield: 92%; [α]_D ^²5 +2.2
(c = 1, DMSO). IR (KBr): 3390, 1598, 1461, 1384, 1168, 1047, 828 cm^-¹. ^¹H NMR (300 MHz, CDCl₃): δ = 3.24 (s, 16 H), 3.68-3.82 (m, 16 H), 5.07 (s, 8 H), 5.11 (s, 16 H), 5.18 (d, J = 4.8 Hz, 8 H), 5.32 (d, J = 3.6 Hz, 12 H), 5.44 (d, J = 9.0 Hz, 8 H), 5.54 (s, 8 H), 5.57 (s, 4 H), 6.45 (s, 4 H), 6.62 (s, 8 H), 6.71 (s, 2 H), 6.77 (s, 4 H), 6.81 (d, J = 8.4 Hz, 2 H), 7.10 (t, J = 7.8 Hz, 2 H), 7.24 (t, J = 6.6 Hz, 2 H), 7.52 (s, 2 H), 7.66 (d, J = 8.7 Hz, 2 H), 7.83 (d, J = 7.5 Hz, 2 H), 7.96 (d, J = 8.4 Hz, 2 H), 8.29 (s, 4 H), 8.32 (s, 8 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 52.8, 60.5, 60.8, 62.2, 69.2, 72.0, 76.6, 79.4, 87.3, 100.9, 107.1, 115.7, 119.3, 123.8, 124.0, 124.3, 124.8, 125.7, 126.3, 127.8, 127.9, 128.8, 129.2, 129.3, 133.0, 137.6, 138.0, 142.4, 142.7, 143.5, 153.2, 159.1, 159.2. MS (MALDI-TOF): m/z = 3451 [M⁺]. Anal. Calcd for C₁₅₂H₁₇₂N₄₂O₅₄: C, 52.90; H, 5.02; N, 17.05. Found: C, 52.89; H, 5.02; N, 17.02.