Stereoselective α-Glycosylation with 3-O-Acetylated d-Gluco Donors

Abstract

The effect of a 3-O-acetyl group on the stereoselectivity of α-glycosylation with 2-O-benzylated d-gluco glycosyl donors was studied. It was shown that 3-O-acetylated donors gave α-anomers predominantly or exclusively, whereas glycosylation with the corresponding per-O-benzylated donors afforded mixtures of comparable amounts of α- and β-anomers. The higher α-stereoselectivity in the first case was accounted for by the remote anchimeric assistance of the 3-O-acetyl group, which was confirmed by theoretical calculations.

Key words

carbohydrates - glycosylations - remote participation - stereoselectivity - α-glucosylation

References and Notes

• 1 Demchenko AV. Lett. Org. Chem.  2005,  2:  580 
• 2 Nukada T. Berces A. Zgierski M. Whitfield DM. J. Am. Chem. Soc.  1998,  120:  13291 
• 3 Toshima K. Tatsuta K. Chem. Rev.  1993,  93:  1503 
• 4 Demchenko AV. Curr. Org. Chem.  2003,  7:  35 
• 5 Ishikawa T. Fletcher HG. J. Org. Chem.  1969,  34:  563 
• 6 Fletcher JM. Schuerch C. J. Am. Chem. Soc.  1972,  94:  604 
• 7 Demchenko AV. Rousson E. Boons G.-J. Tetrahedron Lett.  1999,  40:  6523 
• 8 Dejter-Juszynski M. Flowers HM. Carbohydr. Res.  1972,  23:  41 
• 9 Dejter-Juszynski M. Flowers HM. Carbohydr. Res.  1973,  28:  61 
• 10 De Meo C. Kamat MN. Demchenko AV. Eur. J. Org. Chem.  2005,  706 
• 11 Yamanoi T. Nakamura K. Takeyama H. Yanagihara K. Inazu T. Bull. Chem. Soc. Jpn.  1994,  67:  1359 
• 12 Kováč P. Palovčík R. Carbohydr. Res.  1977,  54:  C11 
• 13 Hirsch J. Koóš M. Kovač P. Carbohydr. Res.  1998,  310:  145 
• 14 Wiesner K. Tsai TYR. Ren A. Kumar R. Tsubuki V. Helv. Chim. Acta  1983,  66:  2632 
• 15 Tsai TYR. Jin H. Wiesner K. Can. J. Chem.  1984,  62:  1403 
• 16 Thiem J. Klaffke W. Top. Curr. Chem.  1990,  154:  284 
• 17 Gerbst AG. Ustuzhanina NE. Grachev AA. Khatuntseva EA. Tsvetkov DE. Whitfield DM. Berces A. Nifantiev NE. J. Carbohydr. Chem.  2001,  20:  821 
• 18 Komarova B. Tsvetkov Y. Knirel Y. Zähringer U. Pier G. Nifantiev N. Tetrahedron Lett.  2006,  in press 
• 21 Takeo K. Aspinall GO. Brennan P. Chatterjee D. Carbohydr. Res.  1986,  150:  133 
• 23 Fukase K. Hase S. Ikenaka T. Kusumoto S. Bull. Chem. Soc. Jpn.  1992,  65:  436 

19

A mixture of donor 1 (53 mg, 0.069 mmol), acceptor 7 (17 mg, 0.048 mmol), and MS AW-300 (76 mg) in CH₂Cl₂ (0.8 mL) was treated with a soln of AgOTf (9 mg, 0.034 mmol) in toluene (110 µL) overnight at r.t. under argon. The reaction mixture was filtered through celite, the filtrate was washed with 1 M Na₂S₂O₃, a sat. soln of NaHCO₃, and concentrated. After purification by chromatography (silica gel, toluene-EtOAc, 12:1) a mixture of α- and β-anomers 10 and 11 (40 mg, 0.045 mmol, 95%, 2:1) was obtained. The ratio of 10/11 was determined by the integration of the H-3 signal intensities (α, 5.21 ppm; β, 5.32 ppm) in the ¹H NMR spectra. Selected signals for 10: ¹H NMR (250 MHz, CDCl₃): δ = 4.82 (d, 1 H, J _{1 ′ ,2 ′} = 4.0 Hz, H-1′), 4.88 (d, 1 H, J _1,2 = 3.5 Hz, H-1), 5.21 (dd, 1 H, J _2,3 = 11.2 Hz, J _3,4 = 2.7 Hz, H-3). Selected signals for 11: ¹H NMR (250 MHz, CDCl₃): δ = 4.39 (d, 1 H, J _{1 ′ ,2 ′} = 9.4 Hz, H-1′), 4.90 (d, 1 H, J _1,2 = 3.8 Hz, H-1), 5.32 (dd, 1 H, J _2,3 = 11.0 Hz, J _3,4 = 2.8 Hz, H-3).

20

To a stirred mixture of acceptor 7 (33 mg, 0.095 mmol), donor 2 (50 mg, 0.075 mmol), and MS AW-300 (140 mg) in anhyd CH₂Cl₂ (2 mL) a soln of AgOTf (10 mg, 0.039 mmol) in anhyd toluene (0.1 mL) was added. The reaction was monitored by TLC, when donor 2 was consumed, a further portion of the donor (29 mg, 0.044 mmol) in anhyd CH₂Cl₂ and AgOTf (6 mg, 0.023 mmol) were added. The reaction mixture was stirred at r.t. for 2 d and then filtered through celite. The filtrate was washed with 1 M Na₂S₂O₃, a sat. soln of NaHCO₃, and concentrated. After purification by column chromatography (silica gel; toluene-EtOAc, 12:1) and gel-permeation chromatography (BioBeads SX-3, toluene) a mixture of α- and β-isomers 12 and 13 (71 mg, 90%, 4:1) was obtained. The α/β ratio was determined by the inte-gration of the H-3′ signals (α, 5.58 ppm; β, 5.18 ppm) in the ¹H NMR spectra. Selected signals for 12: ¹H NMR (250 MHz, CDCl₃): δ = 4.83 (d, 1 H, J _1,2 = 3.5 Hz, H-1), 4.87 (d, 1 H, J _{1 ′ ,2 ′} = 3.3 Hz, H-1′), 5.18 (dd, 1 H, J _2,3 = 11.3 Hz, H-3), 5.58 (t, 1 H, J _{2 ′ ,3 ′} = 9.8 Hz, H-3′). Selected signals for 13: ¹H NMR (250 MHz, CDCl₃): δ = 4.90 (d, 1 H, J _1,2 = 3.5 Hz, H-1), 5.18 (t, 1 H, J _{2 ′ ,3 ′} = 10.0 Hz, H-3′).

22

Glycosylation with Glucuronyl Donors 3 and 4; General Procedure. A mixture of glucuronyl bromide (0.052 mmol; 28 mg for 3, 26 mg for 4), acceptor 8 (12 mg, 0.05 mmol) and MS 4 Å (200 mg) in anhyd CH₂Cl₂ (2 mL) was stirred at r.t. for 30 min. Then AgOTf (15 mg, 0.057 mmol) was added at -30 °C. The mixture was stirred for 15 min at -30 °C, then quenched with Et₃N (0.1 mL), and filtered through celite. The filtrate was washed with 1 M Na₂S₂O₃, H₂O, dried over Na₂SO₄, and concentrated. Column chromatography (toluene-EtOAc, 15:1) of the residue afforded disaccharides. The α/β ratios were determined by integration of the signals corresponding to H-1′ in the ¹H NMR spectra. Selected signals for 14: ¹H NMR (250 MHz, CDCl₃): δ = 4.92 (d, 1 H, J _1,2 = 3.1 Hz, H-1), 5.25 (d, 1 H, J _{1 ′ 2 ′} = 3.5 Hz, H-1′). Selected signals for 15: ¹H NMR (250 MHz, CDCl₃): δ = 4.98 (s, 1 H, H-1), 5.56 (d, 1 H, J _{1 ′ ,2 ′} = 8.5 Hz, H-1′). Selected signals for 16: ¹H NMR (250 MHz, CDCl₃): δ = 1.35 (d, 3 H, 3 × H-6), 1.98 (s, 3 H, COCH₃), 3.52 (dd, 1 H, J _{1 ′ ,2 ′} = 3,6 Hz, J _{2 ′ ,3 ′} = 10.0 Hz, H-2′), 3.73 (s, 3 H, CH₃), 3.76 (m, 2 H, H-2, H-4′), 4.04-4.22 (m, 5 H, H-3, H-4, H-5, CH ₂CH=CH₂), 4.42-4.80 (m, 5 H, H-5′, 2 × CH ₂Ph), 4.88 (d, 1 H, J _1,2 = 3.5 Hz, H-1), 5.20 and 5.35 (2 dd, 2 H, CH₂CH=CH ₂), 5.30 (d, 1 H, J _{1 ′ ,2 ′} = 3.6 Hz, H-1′), 5.56 (t, 1 H, J _{2 ′ ,3 ′} = J _{3 ′ ,4 ′} = 9.6 Hz, H-3′), 5.92 (m, 1 H, CH₂CH=CH₂), 7.24-7.35 (m, 10 H, 2 × Ph).

24

Glycosylation with Xylosyl Donors 5 and 6; General Procedure. A mixture of xylosyl trichloroacetimidate (0.071 mmol; 40 mg for 5: 36 mg for 6), acceptor 9 (26 mg, 0.07 mmol) and MS 4 Å (200 mg) in anhyd CH₂Cl₂ (2 mL) was stirred at r.t. for 30 min. Then a 0.1 M solution of TMSOTf in anhyd CH₂Cl₂ (10 µL) was added at -30 °C. The mixture was stirred for 15 min at -30 °C, then quenched with Et₃N (0.1 mL), and filtered through celite. The filtrate was washed with H₂O, dried over Na₂SO₄, and concentrated. Column chromatography (toluene-EtOAc, 10:1) of the residue afforded disaccharides. The α/β ratios were determined by integration of the signals corresponding to H-1′ in the ¹H NMR spectra. Selected signals for 17: ¹H NMR (250 MHz, CDCl₃): δ = 5.58 (d, 1 H, J _{1 ′ ,2 ′} = 3.5 Hz, H-1′). Selected signals for 18: ¹H NMR (250 MHz, CDCl₃): δ = 4.93 (d, 1 H, J _{1 ′ ,2 ′} = 9.5 Hz, H-1′). ¹H NMR data for 19: ¹H NMR (250 MHz, CDCl₃): δ = 3.36 (dd, 1 H, J _{1 ′ ,2 ′} = 3.3 Hz, J _{2 ′ ,3 ′} = 9.6 Hz, H-2′), 3.43-3.74 (m, 7 H, H-2, H-4, H-4′, 2 × H-5, 2 × H-5′), 3.91-4.20 (m, 3 H, H-3, CH ₂CH=CH₂), 4.31-4.79 (m, 9 H, 4 × CH ₂Ph, H-1), 5.20-5.35 (m, 2 H, CH₂CH=CH ₂), 5.54 (t, 1 H, J _{2 ′ ,3 ′} = J _{3 ′ ,4 ′} = 9.6 Hz, H-3′), 6.67 (d, J _{1 ′ ,2 ′} = 3.3 Hz, H-1′), 5.92 (m, 1 H, CH₂CH=CH₂), 7.08-7.50 (m, 20 H, 4 × Ph).