Polyhydroxylated Bicyclic Ureas from Glycosyl Isocyanides

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.

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

References and Notes

<A NAME="RG40105ST-1A">1a</A> Platt FM. Neises GR. Reinkensmeier GM. Townsend JV. Perry H. Proia RL. Winchester B. Dwek RA. Butters TD. Science  1997,  276:  428 

<A NAME="RG40105ST-1B">1b</A> Humphries MJ. Matsumoto K. White SL. Olden K. Proc. Natl. Acad. Sci. U.S.A.  1986,  83:  1752 

<A NAME="RG40105ST-2">2</A> Avalos M. Babiano R. Cintas P. Jiménez JL. Palacios JC. Valencia C. Tetrahedron  1993,  49:  2655 

<A NAME="RG40105ST-3A">3a</A> Wiley PF. Herr RR. Jahnke H. Chidester CG. Mizsak SA. Spaulding LB. Argoudelis AD. J. Org. Chem.  1979,  44:  9 

<A NAME="RG40105ST-3B">3b</A> Ellestad GA. Cosulich DB. Broschard RW. Martin JH. Kunstmann MP. Morton GO. Lancaster JE. Fulmor W. Lovell FM. J. Am. Chem. Soc.  1978,  100:  2515 

<A NAME="RG40105ST-4">4</A> Pérez PD. García-Moreno MI. Mellet CO. García Fernández J. Eur. J. Org. Chem.  2005,  2903 

<A NAME="RG40105ST-5">5</A> Kayakiri H. Takase S. Shibata T. Okamoto M. Terano H. Hashimoto M. J. Org. Chem.  1989,  54:  4015 

<A NAME="RG40105ST-6">6</A> Laufer S. Wagner G. Kotschenreuther D. Angew. Chem. Int. Ed.  2002,  41:  2290 

<A NAME="RG40105ST-7">7</A> Morel CJ. Helv. Chim. Acta  1961,  44:  403 

<A NAME="RG40105ST-8">8</A> Kovacs J. Pinter I. Messmer A. Toth G. Duddeck H. Carbohydr. Res.  1987,  166:  101 

<A NAME="RG40105ST-9A">9a</A> Prosperi D. Ronchi S. Lay L. Rencurosi A. Russo G. Eur. J. Org. Chem.  2004,  395 

<A NAME="RG40105ST-9B">9b</A> Prosperi D. Ronchi S. Panza L. Rencurosi A. Russo G. Synlett  2004,  1529 

<A NAME="RG40105ST-10">10</A> Johnson HW. Krutzsch H. J. Org. Chem.  1967,  32:  1939 

<A NAME="RG40105ST-11">11</A>

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.

<A NAME="RG40105ST-12">12</A>

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.