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Synlett 2009(3): 425-428  
DOI: 10.1055/s-0028-1087539
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

α-Selective Sialylations with N-Acetyl-5-N,4-O-Oxazolidinone-Protected p-Toluenethiosialoside

Fen-fen Liang, Li Chen, Guo-wen Xing*
Department of Chemistry, Beijing Normal University, Beijing 100875, P. R. of China
Fax: +86(10)58802075; e-Mail: gwxing@bnu.edu.cn;
Further Information

Publication History

Received 18 August 2008
Publication Date:
21 January 2009 (online)

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Abstract

A novel N-acetyl-5-N,4-O-oxazolidinone-protected p-toluenethiosialoside was readily prepared from sialic acid and p-toluenethiol. It was demonstrated that the p-toluenethiosialoside could be successfully applied to the α-selective sialylations with various glycosyl acceptors in good yields. In the coupling of N-acetyl-5-N,4-O-oxazolidinone-protected p-toluenethiosialoside and gluco alcohol, a quantitative reaction yield and high α-selectivity were obtained in dichloromethane-acetonitrile (2:1) at -40 ˚C.

Key words

p-toluenethiosialoside - oxazolidinone - sialic acid

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Donor 1 was prepared similarly as literature described. [¹4] Compound characterization data for 5: ¹H NMR (500 MHz, CD3OD): δ = 7.47 (d, J = 7.7 Hz, 2 H), 7.22 (d, J = 7.7 Hz, 2 H), 4.06 (dt, J = 11.9, 3.3 Hz, 1 H), 3.83 (m, 3 H), 3.67-3.69 (m, 2 H), 3.67 (s, 3 H), 3.55 (d, J = 8.8 Hz, 1 H), 3.14 (dd, J = 11.7, 3.6 Hz, 1 H, H-3eq), 2.38 (s, 3 H), 2.21 (t, J = 12.2 Hz, 1 H, H-3ax). ¹³C-APT NMR (125 MHz, CD3OD): δ = 169.1, 160.9, 140.5, 136.3, 129.3, 125.1, 87.8, 78.3, 78.2, 71.5, 70.0, 63.1, 57.1, 52.2, 36.6, 19.9. HRMS: m/z calcd for C18H23NO8SNa [M + Na]+: 436.10421; found. 436.10364.
Compound 1: ¹H NMR (500 MHz, CDCl3): δ = 7.45 (d, J = 7.9 Hz, 2 H), 7.18 (d, J = 7.9 Hz, 2 H), 5.55 (d, J = 5.8 Hz, 1 H), 5.38 (m, 1 H), 4.45 (dd, J = 12.2, 2.6 Hz, 1 H), 4.36 (d, J = 9.4 Hz, 1 H), 4.23 (m, 1 H), 3.98 (m, 1 H), 3.65 (s, 3 H), 3.63 (m, 1 H), 3.10 (dd, J = 12.1, 3.5 Hz, 1 H, H-3eq), 2.48 (s, 3 H), 2.39 (s, 3 H), 2.19 (s, 3 H), 2.14 (m, 1 H, H-3ax), 2.11 (s, 3 H), 2.10 (s, 3 H). ¹³C-APT NMR (125 MHz, CDCl3): δ = 171.9, 170.6, 170.3, 170.0, 168.2, 153.4, 140.6, 136.3, 129.7, 124.7, 87.8, 77.4, 75.7, 72.6, 70.7, 62.5, 59.1, 53.1, 36.5, 24.7, 21.3, 21.1, 20.9, 20.8. HRMS: m/z calcd for C26H31NO12SNa [M + Na]+: 604.14647; found. 604.14590.

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General Sialylation Procedure (with the Coupling Between 1 and 6 as Example)
To a mixture of donor 1 (40.0 mg, 0.07 mmol, 1.0 equiv), acceptor 6 (38.4 mg, 0.08 mmol, 1.2 equiv), and activated 4 Å powdered MS, was added anhyd CH2Cl2-MeCN (2:1, 3 mL). The resulted solution was stirred for 0.5 h at r.t. under Ar, and then cooled to -40 ˚C followed by addition of NIS (37.7 mg, 0.17 mmol, 2.4 equiv) and TfOH (6.0 µL, 0.07 mmol, 1.0 equiv). The reaction was stirred at -40 ˚C for 1 h. After quenched with Et3N (0.1 mL), the mixture was diluted with CH2Cl2, filtered through Celite, washed with 20% aq Na2S2O3 solution, dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by column chromatography on SiO2 eluting with hexane-EtOAc system to give the coupling product.

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Compound 17: ¹H NMR (500 MHz, CDCl3): δ = 5.60 (d, J = 7.2 Hz, 1 H), 5.40 (dt, J = 6.9, 2.8 Hz, 1 H), 5.34 (d, J = 3.1 Hz, 1 H), 5.12 (m, 1 H), 4.55 (d, J = 9.4 Hz, 1 H), 4.42-4.33 (m, 2 H), 4.13 (m, 1 H), 4.01 (m, 1 H), 3.79 (s,
3 H), 3.71 (t, J = 9.8 Hz, 1 H), 3.62 (m, 1 H), 3.48-3.35 (m, 2 H), 2.90 (dd, J = 12.0, 3.2 Hz, 1 H, H-3eq), 2.49 (s, 3 H), 2.15 (s, 3 H), 2.12 (s, 3 H), 2.03 (s, 3 H), 1.01 (s, 3 H), 0.96 (d, J = 6.9 Hz, 3 H), 0.79 (s, 3 H), 0.78 (d, J = 5.7 Hz, 3 H).

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CCDC 693369 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.