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Synlett 2006(5): 0786-0788  
DOI: 10.1055/s-2006-933101
LETTER
© Georg Thieme Verlag Stuttgart · New York

Polyhydroxylated Bicyclic Ureas from Glycosyl Isocyanides

Davide Prosperi*
Istituto di Scienze e Tecnologie Molecolari - CNR, via Golgi 19, 20133 Milano, Italy
Fax: +39(02)50314061; e-Mail: davide.prosperi@unimi.it;
Further Information

Publication History

Received 16 December 2005
Publication Date:
09 March 2006 (online)

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Abstract

cis-2-Deoxy-2-acetamido glycosyl isocyanides are shown to be excellent precursors for the rapid preparation of bicyclic pyranoid glycosyl ureas, exploiting, in this case, an anomalous nucleophilic reactivity of the acetamido group.

Key words

glycosyl urea - stereoselective synthesis - isocyanides - glycoimidazolidinones - intramolecular addition

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All new compounds have been characterized by proton and carbon NMR spectroscopy. Spectroscopic data for selected compounds.
Compound 5: [α]D 20 +52.9 (c 1, CHCl3); mp 160-162 °C. 1H NMR (400 MHz, CDCl3): δ = 2.01, 2.02, 2.06 (3 s, 9 H, 3 × OAc), 2.42 (s, 3 H, NAc), 3.74 (dt, 1 H, J = 4.0, 7.6 Hz, H-5), 4.14 (dd, 1 H, J = 7.2, 11.7 Hz, H-6a), 4.23 (dd, 1 H, J = 4.3, 11.7 Hz, H-6b), 4.56 (t, 1 H, J = 6.0 Hz, H-2), 4.96 (t, 1 H, J = 4.5 Hz, H-4), 5.19 (d, 1 H, J = 6.8 Hz, H-1), 5.62 (t, 1 H, J = 4.5 Hz, H-3), 6.73 (s, 1 H, NH). 13C NMR (100 MHz, APT, CDCl3): δ = 20.64, 20.73 (3 × CH3CO), 23.63 (NCOCH3), 53.04 (C-2), 64.30 (C-6), 64.42 (C-4), 66.59 (C-3), 74.57 (C-5), 77.17 (C-1), 155.15 (NCON), 169.14, 169.25, 170.46, 170.60 (4 acetyl C=O). Anal. Calcd for C15H20N2O9 (372.12): C, 48.39; H, 5.41; N, 7.52. Found: C, 48.21; H, 5.38; N, 7.61.
Compound 6: [α]D 20 +9.0 (c 0.25, CHCl3). 1H NMR (400 MHz, CDCl3): δ = 1.96, 2.01, 2.05 (3 s, 9 H, 3 × OAc), 2.44 (s, 1 H, NAc), 3.86 (m, 1 H, H-5), 4.13 (dd, 1 H, J = 5.8, 12.1 Hz, H-6a), 4.18 (dd, 1 H, J = 3.2, 12.1 Hz, H-6b), 4.42 (dd, 1 H, J = 3.4, 7.8 Hz, H-2), 4.92 (dd, 1 H, J = 3.3, 7.6 Hz, H-4), 5.49 (s, 1 H, NH), 5.50 (d, 1 H, J = 6.7 Hz, H-1), 5.55 (t, 1 H, J = 3.4 Hz, H-3). 13C NMR (100 MHz, APT, CDCl3): δ = 20.60, 20.75, 20.83 (3 × CH3CO), 24.34 (NCOCH3), 53.62 (C-2), 63.62 (C-6), 67.02 (C-4), 67.30 (C-3), 67.76 (C-5), 76.46 (C-1), 154.82 (NCON), 169.02, 169.08, 170.50, 170.54 (4 acetyl C=O). Anal. Calcd for C15H20N2O9 (372.12): C, 48.39; H, 5.41; N, 7.52. Found: C, 48.09; H, 5.45; N, 7.41.

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Deprotection of 5 gave the corresponding water-soluble glycosylimidazolidinone 13. Compound 5 (50 mg, 0.134 mmol) was dissolved in MeOH (1 mL), and Amberlite IRA 400 resin (OH- form freshly prepared, 100 mg) was added in one portion. After 1 h, the starting material disappeared (TLC: EtOAC-MeOH-H2O, 8:3:1). Resin was filtered off and the solvent was evaporated to give 13 quantitatively, which was purified by Sephadex chromatography with a G10-120 column (eluent: H2O) and lyophilized. Mp 154-156 °C. Selected NMR data for compound 13: 1H NMR (400 MHz, D2O): δ = 3.30 (ddd, 1 H, J = 2.5, 6.8, 9.5 Hz, H-5), 3.50 (t, 1 H, J = 9.5 Hz, H-4), 3.57 (dd, 1 H, J = 6.8, 12.2 Hz, H-6a), 3.81 (dd, 1 H, J = 2.5, 12.2 Hz, H-6b), 3.82 (dd, 1 H, J = 5.3, 9.5 Hz, H-3), 4.05 (dd, 1 H, J = 4.0, 5.3 Hz, H-2), 5.14 (d, 1 H, J = 4.0 Hz, H-1). 13C NMR (100 MHz, APT, D2O): δ = 57.79 (C-2), 60.87 (C-6), 67.19 (C-4), 70.84 (C-3), 74.65 (C-5), 81.64 (C-1), 165.03 (NCON). Anal. Calcd for C7H12N2O5 (204.18): C, 41.18; H, 5.92; N, 13.72. Found: C, 42.01; H, 5.38; N, 12.97.