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Synlett 2006(3): 0455-0459  
DOI: 10.1055/s-2006-926264
LETTER
© Georg Thieme Verlag Stuttgart · New York

A One-Step Synthesis of Azide-Tagged Carbohydrates: Versatile ­Intermediates for Glycotechnology

Aditya K. Sanki, Lara K. Mahal*
Department of Chemistry and Biochemistry, The University of Texas at Austin, 1 University Station, A5300, Austin, TX 78712-0165, USA
Fax: +1(512)4718696; e-Mail: lmahal@cm.utexas.edu;
Further Information

Publication History

Received 22 November 2005
Publication Date:
06 February 2006 (online)

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Abstract

Herein we describe a simple and practical methodology for accessing both the α-anomers (d-mannose, N-acetyl-d-glucosamine, N-acetyl-d-galactosamine, d-lactose) and α- and β-anomers (d-glucose, d-galactose, l-fucose) of 2′-azidoethyl and azidotriethylene glycol glycosides using free sugars and Dowex 50 (resin) as an efficient catalyst. These azidoalkyl glycosides are increasingly useful synthetic intermediates for glycotechnology.

Key words

azidoethyl glycosides - azidotriethylene glycol glycosides - glycotechnology - resin-catalyzed glycosylation

    References and Notes

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12

Procedure for the Reduction of Azidoalkyl Glycosides.
To a well-stirred solution of the azidoalkyl glycoside in MeOH (4 mL/mmol) was added Pd/C (40 mg/mmol) and a balloon of H2 (g). The reaction mixture was monitored for 12 h. After completion of the reaction (TLC), the mixture was filtered through Celite® and the filtrate was concentrated to dryness to give the title compound quantitatively.
2′-Aminoethyl-α- d-lactoside(7a): yield: 100%; a yellow fluffy material (hygroscopic). IR (KBr plate): 3370 (br, OH + NH2) cm-1. 1H NMR (300 MHz, DMSO-d 6 + D2O): δ = 4.65 (1 H, d, J = 3.9 Hz, H-1), 4.12 (1 H, d, J = 8.1 Hz, H-1′), 4.09 (1 H, d, J = 7.5 Hz), 3.71-3.30 (10 H, m), 3.23-2.96 (3 H, m), 2.67 (2 H, m). HRMS (EI): m/z calcd for C14H28NO11 [M + H]+: 386.1662; found: 386.1662.

15

General Procedure for the Acetylation of Azidoalkyl Glycosides. To a well-stirred solution of the azidoalkyl glycoside in dry pyridine (4 mL/mmol) under N2 was added DMAP (catalytic amount). Then, Ac2O (10-12 equiv) was added to the mixture dropwise by syringe and the reaction was stirred for 2-12 h at ambient temperature. After completion (TLC, charred in 2% methanolic H2SO4), a small amount of ice was added and the reaction was stirred for ca. 30 min. The reaction mixture was then poured into H2O (30 mL/mmol) and extracted with CHCl3 (3 × 40 mL). The combined organic layers were dried over anhydrous Na2SO4, filtered and the filtrate was concentrated to dryness in vacuo. Column chromatography (230-400 mesh) was carried out using acetone-CHCl3-hexanes (1:1:8) to separate both
α- and β-isomers.

16

Characterization of Compounds.
The full characterization for one representative compound for each glycoside (16α for the 2′-azidoethyl glycosides and 18α,β for the azidotriethylene glycosides) is given. Key data are shown for all other unknown compounds. For 13C NMR all methylenes (CH2) were identified by DEPT. NMR exchange data for the anomeric protons of the unprotected mixtures are shown in ref. 17.
2′-Azidoethyl-2,3,4,6-tetra- O -acetyl-α- d -galactoside (16α). An amorphous hygroscopic solid. IR (CHCl3): 2931, 2108 (N3), 1747 (C=O) cm-1. 1H NMR (300 MHz, CDCl3): δ = 5.47 (1 H, m), 5.36 (1 H, dd, J = 3.3, 10.5 Hz), 5.16 (1 H, s, H-1), 5.13 (1 H, dd, J = 8.4, 15.0 Hz), 4.25 (1 H, t, J = 6.6 Hz), 4.10 (2 H, d, J = 6.9 Hz), 3.86 (1 H, m), 3.63 (1 H, m), 3.52-3.34 (2 H, m), 2.14 (3 H, s, CH3), 2.08 (3 H, s, CH3), 2.04 (3 H, s, CH3), 1.98 (3 H, s, CH3). 13C NMR (75.47 MHz, CDCl3): δ = 170.5 (C=O), 170.4 (C=O), 170.2 (C=O), 169.9 (C=O), 96.4 (C-1), 68.0, 67.8, 67.4, 67.3 (CH2), 66.5, 61.7 (CH2), 50.4 (CH2), 20.7 (CH3), 20.7 (CH3), 20.62 (CH3), 20.6 (CH3). HRMS (EI): m/z calcd for C16H24N3O10 [M + H]+: 418.1462; found: 418.1451.
2′-Azidoethyl-2,3,4-tri- O -acetyl-β- l-fucoside (17β). A colorless gum. IR (CHCl3): 2106 (N3), 1752 (C=O) cm-1. 1H NMR (300 MHz, CDCl3): δ = 4.52 (1 H, d, J = 8.1 Hz, H-1). 13C NMR (75.47 MHz, CDCl3): δ = 170.6 (C=O), 170.1 (C=O), 169.5 (C=O), 100.8 (C-1), 68.2 (CH2), 50.5 (CH2). HRMS (EI): m/z calcd for C14H22N3O8 [M + H]+: 360.1407; found: 360.1411.

2-[2-(2-Azidoethoxy)ethoxy]ethyl-2,3,4,6-tetra- O -acetyl-α- d -glucoside (18α) and 2-[2-(2-Azidoethoxy)ethoxy]eth-yl-2,3,4,6-tetra- O -acetyl-β- d -glucoside (18β).
Compound 18α: a colorless gum. IR (CHCl3): 2109 (N3), 1750 (C=O) cm-1. 1H NMR (300 MHz, CDCl3): δ = 5.43 (1 H, t, J = 10.2 Hz), 5.08 (1 H, d, J = 3.6 Hz, H-1), 5.01 (1 H, t, J = 10.2 Hz), 4.81 (1 H, dd, J = 3.6, 10.2 Hz), 4.21 (1 H, dd, J = 3.9, 12.0 Hz), 4.06 (2 H, m), 3.74 (1 H, m), 3.62 (9 H, m), 3.35 (2 H, t, J = 5.4 Hz), 2.03 (3 H, s, CH3), 2.01 (3 H, s, CH3), 1.97 (3 H, s, CH3), 1.95 (3 H, s, CH3). 13C NMR (75.47 MHz, CDCl3): δ = 170.4 (C=O), 169.9 (C=O), 169.4 (C=O), 95.6 (C-1), 70.6 (CH2), 70.5 (CH2), 69.9, 68.3, 67.5 (CH2), 67.0, 61.7 (CH2), 50.5 (CH2), 20.5 (CH3), 20.49 (CH3), 20.42 (CH3). HRMS (EI): m/z calcd for C20H32N3O12 [M + H]+: 506.1986; found: 506.1982.
Compound 18β: a colorless gum. IR (CHCl3): 2108 (N3), 1755 (C=O) cm-1. 1H NMR (300 MHz, CDCl3): δ = 5.17 (1 H, t, J = 9.3 Hz), 5.04 (1 H, t, J = 9.6 Hz), 4.95 (1 H, dd, J = 8.1, 9.6 Hz), 4.58 (1 H, d, J = 8.1 Hz, H-1), 4.22 (1 H, dd, J = 4.5, 12.3 Hz, C6-H′), 4.09 (1 H, dd, J = 2.4, 12.3 Hz, C6-H), 3.90 (1 H, m, C5-H), 3.75-3.56 (10 H, m), 3.36 (2 H, t, J = 5.1 Hz), 2.05 (3 H, s, CH3), 2.01 (3 H, s, CH3), 1.98 (3 H, s, CH3), 1.96 (3 H, s, CH3). 13C NMR (75.47 MHz, CDCl3): δ = 170.7 (C=O), 170.3 (C=O), 169.5 (C=O), 169.4 (C=O), 100.9 (C-1), 72.9, 71.8, 71.3, 70.8 (CH2), 70.5 (CH2), 70.1 (CH2), 69.1 (CH2), 68.5, 62.0 (CH2), 50.7 (CH2), 20.8 (CH3), 20.7 (CH3), 20.7 (CH3), 20.6 (CH3). HRMS (EI): m/z calcd for C20H32N3O12 [M + H]+: 506.1986; found: 506.1999.
2-[2-(2-Azidoethoxy)ethoxy]ethyl-2,3,4,6-tetra- O -acetyl-α- d -galactoside (19α) and 2-[2-(2-azidoethoxy)eth-oxy]ethyl-2,3,4,6-tetra- O -acetyl-β- d -galactoside (19β).
Compound 19α: a brown-colored gum. IR (CHCl3): 2108 (N3), 1747 (C=O) cm-1. 1H NMR (300 MHz, CDCl3): δ = 5.12 (1 H, d, J = 1.8 Hz, H-1). 13C NMR (75.47 MHz, CDCl3): δ = 170.5 (C=O), 170.3 (C=O), 170.1 (C=O), 96.3 (C-1), 70.82 (CH2), 70.8 (CH2), 67.7 (CH2), 61.7 (CH2), 50.7 (CH2). HRMS (EI): m/z calcd for C20H32N3O12 [M + H]+: 506.1986; found: 506.1987.
Compound 19β: a colorless gum. IR (CHCl3): 2106 (N3), 1747 (C=O) cm-1. 1H NMR (300 MHz, CDCl3): δ = 4.55 (1 H, d, J = 8.1 Hz, H-1). 13C NMR (75.47 MHz, CDCl3): δ = 170.6 (C=O), 170.4 (C=O), 170.32 (C=O), 169.6 (C=O), 101.5 (C-1), 70.9 (CH2), 70.85 (CH2), 70.8 (CH2), 69.2 (CH2), 61.5 (CH2), 50.8 (CH2). HRMS (EI): m/z calcd for C20H32N3O12 [M + H]+: 506.1986; found: 506.1997.
2-[2-(2-Azidoethoxy)ethoxy]ethyl-2,3,4-tri- O -acetyl-α- l-fucoside (20α) and 2-[2-(2-Azidoethoxy)ethoxy]ethyl-2,3,4-tri- O -acetyl-β-l-fucoside (20β). Compound 20α: a colorless gum. IR (CHCl3): 2107 (N3), 1743 (C=O) cm-1. 1H NMR (300 MHz, CDCl3): δ = 5.03 (1 H, d, J = 1.5 Hz, H-1). 13C NMR (75.47 MHz, CDCl3): δ = 170.4 (C=O), 170.2 (C=O), 169.8 (C=O), 96.0 (C-1), 70.5 (CH2), 70.4 (CH2), 70.0 (CH2), 67.8 (CH2), 50.4 (CH2). HRMS (EI): m/z calcd for C18H30N3O10 [M + H]+: 448.1931; found: 448.1944.
Compound 20β: a colorless gum. IR (CHCl3): 2106 (N3), 1751 (C=O) cm-1. 1H NMR (300 MHz, CDCl3): δ = 4.49 (1 H, d, J = 8.1 Hz, H-1). 13C NMR (75.47 MHz, CDCl3): δ = 170.7 (C=O), 170.2 (C=O), 169.6 (C=O), 101.1 (C-1), 70.7 (CH2), 70.6 (CH2), 70.4 (CH2), 70.0 (CH2), 69.1 (CH2), 50.6 (CH2). HRMS (EI): m/z calcd for C18H30N3O10 [M + H]+: 448.1931; found: 448.1933.
2-[2-(2-Azidoethoxy)ethoxy]ethyl-2- N -acetamido-2-deoxy-α- d -glucoside ( 11). A colorless gum. IR (KBr plate): 3290 (br, OH), 2111 (N3), 1652 (C=O) cm-1. 1H NMR (300 MHz, DMSO-d 6): δ = 4.68 (2 H, t, J = 4.8 Hz, H-1 and 1 H). 13C NMR (75.47 MHz, DMSO-d 6): δ = 169.4 (C=O), 97.0 (C-1), 69.9 (CH2), 69.7 (CH2), 69.5 (CH2), 69.3 (CH2), 66.5 (CH2), 60.8 (CH2), 50.0 (CH2). HRMS (EI): m/z calcd for C14H27N4O8, [M + H]+: 379.1829; found: 379.1833.
2-[2-(2-Azidoethoxy)ethoxy]ethyl-2- N -acetamido-2-deoxy-α- d -galactoside (12α). A brown-colored gum. IR (KBr-plate): 3305 (OH), 2110 (N3), 1646 (C=O) cm-1. 1H NMR (300 MHz, DMSO-d 6): δ = 4.67 (1 H, d, J = 3.6 Hz, H-1). 13C NMR (75.47 MHz, DMSO-d 6): δ = 169.6 (C=O), 97.4 (C-1), 69.8 (CH2), 69.7 (CH2), 69.5 (CH2), 69.3 (CH2), 66.5 (CH2), 60.6 (CH2), 50.0 (CH2). HRMS (EI): m/z calcd for C14H27N4O8 [M + H]+: 379.1829; found: 379.1830.
2-[2-(2-Azidoethoxy)ethoxy]ethyl-α- d -lactoside ( 14). A yellow gum. IR (KBr plate): 3387 (br, OH), 2109 (N3), 1652 (C=O) cm-1. 1H NMR (300 MHz, DMSO-d 6): δ = 4.65 (1 H, t, J = 3.0 Hz, H-1), 4.10 (1 H, d, J = 7.8 Hz, H-1′). 13C NMR (75.47 MHz, DMSO-d 6): δ = 102.5 (C-1), 98.4 (C-1′). HRMS: m/z calcd for C18H34N3O13 [M + H]+: 500.2092; found: 500.2086.

17

¹ H NMR Exchange Data for the Anomeric Position of α/β-Mixtures 8, 10, 13 and α-Glycosides 11 and 14. Compound 8α: 1H NMR (DMSO-d 6 + D2O): δ = 4.63 (1 H, d, J = 3.9 Hz, H-1).
Compound 8β: 1H NMR (DMSO-d 6 + D2O): δ = 4.12 (1 H, d, J = 7.5 Hz, H-1).
Compound 10α: 1H NMR (DMSO-d 6 + D2O): δ = 4.66 (1 H, d, J = 3.0 Hz, H-1).
Compound 10β: 1H NMR (DMSO-d 6 + D2O): δ = 4.08 (1 H, d, J = 7.5 Hz, H-1).
Compound 13α: 1H NMR (DMSO-d 6 + D2O): δ = 4.59 (1 H, d, J = 2.7 Hz, H-1).
Compound 13β: 1H NMR (DMSO-d 6 + D2O): δ = 4.07 (1 H, d, J = 7.2 Hz, H-1).
Compound 11: 1H NMR (DMSO-d 6 + D2O): δ = 4.68 (1 H, d, J = 3.3 Hz, H-1).
Compound 14: 1H NMR (DMSO-d 6 + D2O): δ = 4.64 (1 H, d, J = 3.9 Hz, H-1 and 4.13 (1 H, d, J = 7.8 Hz, H-1′).