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DOI: 10.1055/s-2003-42066
Phenyl 2-Deoxy-2-iodo-1-thio-glycosides: New Glycosyl Donors for the Stereoselective Synthesis of 2-Deoxy-oligosaccharides
Publication History
Publication Date:
07 October 2003 (online)
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Abstract
Phenyl 2-deoxy-2-iodo-1-thioglycosides, prepared from simple pentoses by olefination and iodine-induced cyclization, have proved to be efficient glycosyl donors for the stereoselective synthesis of 2-deoxy-2-iodo-oligosaccharides, which are precursors of 2-deoxy-oligosaccharides.
Key words
2-deoxy-oligosaccharides - glycosylation - stereoselectivity - cyclizations - iodine
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References
Compound 2: To a solution of 4 mmol of the phosphine oxide in 26 mL of THF at -78 ºC, 4.2 mmol of BuLi were added. The mixture was left to stir at low temperature for 30 min. A solution of 1 mmol of 1 in 2 mL of THF was then added dropwise. The mixture was allowed to warm to r.t. overnight. A sat. solution of NH4Cl was then added and the olefination product extrated with Et2O. The combination of ethereal layers was dried with MgSO4 and concentrated. The reaction crude was purified by MPLC (hexane to EtOAc/hexane = 1:3) to render 2 (80% yield) as a mixture of diastereoisomers (E/Z-ratio = 87:13) as a syrup. Compound 2
E: 1H NMR (400 MHz, CDCl3): δ = 7.40-7.15 (m, 20 H, aromatics), 6.46 (d, 1 H, J
2,1 = 15.2 Hz, H-1), 5.87 (dd, 1 H, J
1,2 = 15.2 Hz, J
3,2 = 7.6 Hz, H-2), 4.65 (d, 1 H, J = 12.0 Hz, CH2Ph), 4.57 (d, 1 H, J = 11.4 Hz, CH2Ph), 4.52 (d, 1 H, J = 11.4 Hz, CH2Ph), 4.49 (s, 2 H, CH2Ph), 4.38 (d, 1 H, J = 12.0 Hz, CH2Ph), 4.16 (dd, 1 H, J
5,4 = 8.0 Hz, J
3,4 = 3.6 Hz, H-4), 4.00 (m, 1 H, H-5), 3.58 (m, 3 H, H-3, H-6), 2.76 (d, 1 H, J = 5.2 Hz, OH). 13C NMR (100.6 MHz, CDCl3):
δ = 140.8, 137.7, 137.5, 134.0 (C, aromatics), 130.2-126.0 (CH aromatics, C-1, C-2), 80.4 (C-3), 79.1 (C-4), 74.1, 73.2, 70.7 (CH2Ph), 70.1 (C-6), 69.9 (C-5). Compound 2
Z:
1H NMR (400 MHz, CDCl3): δ = 7.50-7.15 (m, 20 H, aromatics), 6.67 (d, 1 H, J
2,1 = 9.9 Hz, H-1), 6.12 (dd, 1 H, J
1,2 = 9.9 Hz, J
3,2 = 9.3 Hz, H-2), 4.88 (d, 1 H, J = 11.0 Hz, CH2Ph), 4.84 (d, 1 H, J = 11.5 Hz, CH2Ph), 4.73 (d, 1 H, J = 11.0 Hz, CH2Ph), 4.68 (d, 1 H, J = 12.0 Hz, CH2Ph), 4.63 (d, 1 H, J = 11.5 Hz, CH2Ph), 4.58 (d, 1 H, J = 12.0 Hz, CH2Ph), 4.21 (m, 1 H, H-5), 3.85 (dd, 1 H, J
5,4 = 6.9 Hz, J
3,4 = 3.9 Hz, H-4), 3.77 (m, 3 H, H-3, H-6), 3.12 (d, 1 H, J = 5.1 Hz, OH). 13C NMR (100.6 MHz, CDCl3): δ = 140.8, 137.7, 137.5, 134.0 (C, aromatics), 130.2-126.0 (CH aromatics, C-1, C-2), 80.4 (C-3), 79.1 (C-4), 74.1, 73.2, 70.7 (CH2Ph), 70.1 (C-5), 64.9 (C-6).
Compound 3: A 0.175 M suspension of 1.3 mol of KH 30% in dry Et2O was added dropwise to a 0.085 M solution of 2 (1 mol) in dry Et2O at 0 ºC, and the resulting mixture was allowed to stir for 30 min until complete formation of the alcoholate. The mixture was cooled to -78 ºC and a 0.43 M solution of iodine (3 mol) in Et2O was then added. The reaction was allowed to stir at low temperature for 1 h. A solution of Na2S3O3 was then added and the reaction product extracted with Et2O. The combination of the etheral layers was concentrated and the residue purified by radial chromatography to afford 3 (61%) as a yellowish syrup. Compound 3: [α]D 25 +67.8 (c 0.0217, CH2Cl2). 1H NMR (400 MHz, CDCl3): δ = 7.70-7.10 (m, 20 H, aromatics), 5.68 (s, 1 H, H-1), 4.88 (d, 1 H, J = 10.4 Hz, CH2Ph), 4.87 (d, 1 H, J 3,2 = 3.6 Hz, H-2), 4.72 (d, 1 H, J = 11.2 Hz, CH2Ph), 4.70 (d, 1 H, J = 11.6 Hz, CH2Ph), 4.54 (d, 1 H, J = 11.2 Hz, CH2Ph), 4.52 (d, 1 H, J = 10.4 Hz, CH2Ph), 4.48 (d, 1 H, J = 11.6 Hz, CH2Ph), 4.41 (ddd, 1 H, J 4,5 = 8.8 Hz, J 6a,5 = 4.4 Hz, J 6b,5 = 1.6 Hz, H-5), 3.99 (dd, 1 H, J 5,4 = 8.8 Hz, J 3,4 = 8.4 Hz, H-4), 3.85 (dd, 1 H, J 6b,6a = 10.8 Hz, J 5,6a = 4.4 Hz, H-6a), 3.73 (dd, 1 H, J 6a,6b = 10.8 Hz, J 5,6b = 1.6 Hz, H-6b), 3.10 (dd, 1 H, J 4,3 = 8.4 Hz, J 2,3 = 3.6 Hz, H-3). 13C NMR (100.6 MHz, CDCl3): δ = 138.0, 137.2, 133.9 (C, aromatics), 132.0-127.4 (CH, aromatics), 89.6 (C-1), 77.5 (C-3), 76.2 (C-4), 75.3 (CH2Ph), 73.3 (CH2Ph, C-5), 71.0 (CH2Ph), 68.7 (C-6), 34.8 (C-2).
16Compound 5: To a solution of 4 mmol of the phosphine oxide in 26 mL of THF at -78 ºC, 4.2 mmol of BuLi were added. The mixture was left to stir at low temperature for 30 min. A solution of 1 mmol of the 4 in 2 mL of THF was then added dropwise. The mixture was allowed to warm to r.t. first and then heated to reflux. A sat. solution of NH4Cl was then added and the olefination product extrated with Et2O. The combination of ethereal layers was dried with MgSO4 and concentrated. The reaction crude was purified by MPLC (hexane to EtOAc/hexane = 1:3) to render 5 (72% yield) as a mixture of diastereoisomers (E/Z-ratio = 80:20) as a syrup. Compound 5 E: 1H NMR (400 MHz, CDCl3): δ = 7.39-7.25 (m, 20 H, aromatics), 6.54 (d, 1 H, J 2,1 = 15.1 Hz, H-1), 5.94 (dd, 1 H, J 1,2 = 15.1 Hz, J 3,2 = 8.4 Hz, H-2), 4.75 (d, 1 H, J = 10.8 Hz, CH2Ph), 4.67 (d, 1 H, J = 12.0 Hz, CH2Ph), 4.56 (d, 1 H, J = 10.8 Hz, CH2Ph), 4.51 (d, 1 H, J = 12.0 Hz, CH2Ph), 4.48 (d, 1 H, J = 12.0 Hz, CH2Ph), 4.40 (d, 1 H, J = 12.0 Hz, CH2Ph), 4.22 (dd, 1 H, J 2,3 = 8.4 Hz, J 4,3 = 4.4 Hz, H-3), 3.82 (m, 1 H, H-5), 3.69 (dd, 1 H, J 5,4 = 7.6 Hz, J 3,4 = 4.4 Hz, H-4), 3.61 (m, 2 H, H-6), 2.78 (bs, 1 H, OH). 13C NMR (100.6 MHz, CDCl3): δ = 138.2, 138.1, 137.8, 134.6 (C, aromatics), 129.1-126.9 (CH, aromatics), 128.8 (C-1), 128.4 (C-2), 81.3 (C-3), 80.8 (C-4), 74.2, 73.4 (CH2Ph), 70.9 (C-6), 70.8 (C-5), 70.5 (CH2Ph). Compound 5 Z: 1H NMR (400 MHz, CDCl3): δ = 7.39-7.25 (m, 20 H, aromatics), 6.62 (d, 1 H, J 21 = 9.6 Hz, H-1), 6.00 (pseudo t, 1 H, J 12 = J 32 = 9.6 Hz, H-2), 4.89-4.35 (m, 6 H, CH2Ph), 3.91 (m, 1 H, H-5), 3.83 (dd, 1 H, J 54 = 7.6 Hz, J 34 = 3.4 Hz, H-4), 3.71 (dd, 1 H, J 23 = 9.6 Hz, J 43 = 3.4 Hz, H-3), 3.67 (m, 2 H, H-6), 2.85 (bs, 1 H, OH). 13C NMR (100.6 MHz, CDCl3): δ = 138.1, 137.8, 135.5, 134.4 (C, aromatics), 129.8-126.5 (CH, aromatics, C-1, C-2), 80.9 (C-3), 77.1 (C-4), 74.1, 73.3 (CH2Ph), 71.0, 70.8, 70.5 (C-5, C-6, CH2Ph).
18
Compound 6: To a 0.5 M solution of 5 (0.084 g, 0.16 mmol) (E/Z = 2:3) in CH3CN, NaHCO3 (0.48 mmol) was added. The mixture was cooled to 0 ºC and left to stir at this temperature for 5 min. NIS (0.48 mol) was then added and the reaction mixture was allowed to warm to r.t. and stirred for 8 h. The mixture was diluted with Et2O and washed with a sat. solution of Na2S3O3. The combined aqueous layer was extracted with Et2O. The combination of ethereal layers was dried with MgSO4 and concentrated. The residue was purified by radial chromatography to afford 0.060 g (58% yield) as a β/α mixture = 2:3. Compound 6β: [α]D
25 +16.0 (c 0.7708, CH2Cl2). 1H NMR (400 MHz, CDCl3): δ = 7.70-7.20 (m, 20 H, aromatics), 5.11 (d, 1 H, J
2,1 = 10.6 Hz, H-1), 4.92 (d, 1 H, J = 10.4 Hz, CH2Ph), 4.75 (d, 1 H, J = 10.4 Hz, CH2Ph), 4.62 (d, 1 H, J = 11.4 Hz, CH2Ph), 4.60 (d, 1 H, J = 12.4 Hz, CH2Ph), 4.52 (d, 1 H, J = 11.4 Hz, CH2Ph), 4.51 (d, 1 H, J = 12.4 Hz, CH2Ph), 4.18 (m, 1 H, H-3, H-5), 4.02 (dd, 1 H, J
1,2 = 10.4 Hz, J
3,2 = 2.4 Hz, H-2), 3.72 (m, 1 H, H-4, H-6a, H-6b). 13C NMR (100.6 MHz, CDCl3): δ = 138.4, 138.1, 137.6 (C, aromatics), 133.2 (CH, aromatic), 131.7 (C, aromatic), 128.7-127.4 (CH, aromatics), 84.3
(C-1), 78.7 (C-3), 76.1 (C-4), 75.9 (C-5), 75.7, 73.3, 72.2 (CH2Ph), 69.3 (C-6), 31.8 (C-2). Compound 6α (spectroscopical data extracted from the α/β-mixture spectrum): 1H NMR (400 MHz, CDCl3): δ = 7.70-7.20 (m, 20 H, aromatics), 5.32 (d, 1 H, J
2,1 = 5.4 Hz, H-1), 4.91 (d, 1 H, J = 11.6 Hz, CH2Ph), 4.79 (d, 1 H, J = 10.8 Hz, CH2Ph), 4.68 (ddd, 1 H, J
4,5 = 10.0 Hz, J
6a,5 = 2.8 Hz, J
6b,5 = 2.4 Hz, H-5), 4.57 (dd, J
1,2 = 5.6 Hz, J
3,2 = 2.4 Hz, H-2), 4.52 (d, 2 H, J = 10.4 Hz, CH2Ph), 4.42 (d, 1 H, J = 11.2 Hz, CH2Ph), 4.40 (d, 1 H, J = 12.4 Hz, CH2Ph), 4.09 (dd, 1 H, J
2,3 = 2.4 Hz, J
4,3 = 2.4 Hz, H-3), 3.77 (m, 2 H, H-4, H-6a), 3.62 (dd, 1 H, J
6a,6b = 10.8 Hz, J
5,6b = 2.4 Hz, H-6b). 13C NMR (100.6 MHz, CDCl3): δ = 131.4-126.8 (C, CH, aromatics), 90.0 (C-1), 78.1, 76.3, 75.6, 73.5, 72.0, 68.8, 67.7 (C-3, C-4, C-5, C-6, 3 × CH2Ph), 27.0 (C-2).
General Procedure of Glycosylation: A solution of the glycosyl donor (1 mmol) and the glycosyl acceptor (2 mmol) in CH2Cl2 (4 mL) were allowed to stir with 4 Å molecular sieves for 2 h. The mixture was then cooled to -78 ºC, and NIS (3 mmol) and TfOH (0.2 mmol) were added. The mixture was allowed to warm to -40 ºC and stirred for 2-4 h. The reaction mixture was then diluted with CH2Cl2 and washed with a solution of Na2S3O3. The ethereal layer was dried with Na2SO4 and concentrated. The residue was then purified by radial chromatography.