Compound 1

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Synthetic procedure: See article for the definitive version of this procedure and for full experimental details.

Dimethylamine (5.6 M in EtOH, 2.2 mL, 12.32 mmol) was added at room temperature to a solution of phosphoglucosylceramide 12 (51.2 mg, 31 μmol) in CH₂Cl₂ and the mixture was stirred for 30 min. The mixture was partitioned between CH₂Cl₂ and H₂O. The aqueous layer was extracted with CH₂Cl₂ two times and the combined organic layers were dried over MgSO₄. The solvent was evaporated and the residue was dried in a 100 mL round-bottom flask in vacuo overnight.

Pd(OH)₂/C (H₂O ~50%, 63.1 mg), CH₂Cl₂ (10 mL), and isopropanol (10 mL) were added to this residue. The mixture was set under H₂-atmosphere (balloon) and HCO₂H (6 μL, 159 μmol) was added. The mixture was vigorously stirred for 23 h at room temperature. The catalyst was removed by filtration over a short pad of Celite (CH₂Cl₂/isopropanol 1:1) and the solvent was evaporated. Due to incomplete conversion (ESI-MS), Pd(OH)₂/C (H₂O ~50%, 60.2 mg), CH₂Cl₂ (10 mL), and isopropanol (10 mL) were added. The mixture was set under H₂-atmosphere (balloon) and HCO₂H (7 μL, 186 μmol) was added. The mixture was vigorously stirred for 28 h at room temperature. The catalyst was removed by filtration over a short pad of Celite (CH₂Cl₂/isopropanol 1:1) and the solvent was evaporated. Due to incomplete conversion (ESI-MS), Pd(OH)₂/C (H₂O ~50%, 61.3 mg), CH₂Cl₂ (10 mL), and isopropanol (10 mL) were added. The mixture was set under H₂-atmosphere (balloon) and HCO₂H (7 μL, 186 μmol) was added. The mixture was vigorously stirred for 16 h at room temperature. The catalyst was removed by filtration over a short pad of Celite (CH₂Cl₂/isopropanol 1:1) and the solvent was evaporated. Due to incomplete conversion (ESI-MS), Pd(OH)₂/C (H₂O ~50%, 58.6 mg), CH₂Cl₂ (10 mL), and isopropanol (10 mL) were added. The mixture was set under H₂-atmosphere (balloon) and HCO₂H (10 μL, 265 μmol) was added. The mixture was vigorously stirred for 26 h at room temperature. The catalyst was removed by filtration over a short pad of Celite (CH₂Cl₂/isopropanol 1:1) and the solvent was evaporated. As ESI-MS indicated complete conversion, the residue was purified via preparative HPLC (Grace-Vydac 208TP1050 RP C8 50×250 mm, 55 mL/min, MeOH/H₂O 70:30 to 95:5, 27 min) to yield mmPEGC-C22 (1) (8.5 mg, 9.0 mmol, 29%). ¹H NMR (600 MHz, CD₃OD (3.38)): (ppm) = 0.95 (d, J = 6.7 Hz, 6 H (H-16^LCB)), 0.97 (t, J = 6.9 Hz, 3 H (H-22^FA)), 1.23–1-27 (m, 2 H (H-14^LCB)), 1.28–1.52 (m, 52 H (H₂-[4-21]^FA, H₂-[7-13]^LCB, H₂-6^LCB)), 1.60 (non, J = 6.7 Hz, 1 H (H-15^LCB)), 1.57–1.71 (m, 4 H (H₂-3^FA, H₂-5^LCB)), 2.82 (s, 3 H (H₃-3^HG)), 3.23–3.26 (m, 1 H (H-2^Glc)), 3.32 (t, J = 4.9 Hz, 2 H (H₂-2^HG)), 3.44–3.46 (m, 3 H (H-2^FA, H-3^Glc, H-5^Glc)), 3.58–3.61 (m, 1 H (H-4^LCB)), 3.71 (t, J = 6.1 Hz, 1 H (H-3^LCB)), 3.81 (dd, J_AB = 10.3 Hz; J = 3.8 Hz, 1 H (H_A-1^LCB)), 4.09–4.14 (m, 3 H (H_B-1^LCB, H-4^Glc, H_A-6^Glc)), 4.16–4.20 (m, 2 H (H₂-1^HG)), 4.22 (dd, J_AB = 10.7 Hz, J = 5.2 Hz, 1 H (H_B-6^Glc)), 4.28–4.31 (m, 1 H (H-2^LCB)), 4.37 (d, J = 7.8 Hz, 1 H (H-1^Glc)). ¹³C NMR (HSQC-projection) (150 MHz, CD₃OD (47.96)): (ppm) = 13.10 (CH₃ (C-22^FA)), 21.72 (2 CH₃ (C-16^LCB)), 22.41 (CH₂ (C-21^FA)), 24.78 (CH₂), 27.28 (CH₂), 27.79 (CH (C-15^LCB)), 28.0–30.5 (24 CH₂), 31.73 (CH₂), 32.22 (CH₃ (C-3^HG)), 38.97 (CH₂ (C-14^LCB)), 49.67 (CH₂ (C-2^HG)), 50.22 (CH (C-2^LCB)), 60.33 (CH₂ (C-1^HG)), 64.57 (CH₂ (C-6^Glc)), 68.84 (CH₂ (C-1^LCB)), 69.69 (CH), 71.62 (2 CH (C-4^Glc, C-4^LCB)), 74.05 (br, 2 CH (C-2^Glc, C-3^LCB)), 75.43 (CH), 76.33 (CH), 103.48 (CH (C-1^Glc). ³¹P NMR (HMBC-projection) (243 MHz, CD₃OD): (ppm) = 0.69. ESI-MS: m/z (10 V) = 942.1 [M+H]⁺, 1882.3 [2M+H]⁺. [α]_D²⁰ = +2 (c = 0.04, MeOH). HRMS: C₄₈H₉₇N₂O₁₃P [M−H]⁻: calcd.: 939.6650, found: 939.6605.