Reference
Several lipids with a pseudo cyclic framework are reported in the literature:
1a
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12
Synthesis of 1a: To a solution of 15a (19 mg, 0.101 mmol) and Et3N (10.2 mg, 0.101 mmol) in dry THF (1.0 mL) was added N-succinimidyl ester of hexadecanedioic acid (15 mg, 0.054 mmol) at r.t. After 24 h, the reaction mixture was concentrated under reduced pressure to give a residue. The residue was purified by column chromatography [silica, EtOAc-MeOH-n-hexane (100:10:100 to 100:5:0)] to give 1a (23 mg, 74%).
Synthesis of 1b: To a solution of dotriacontanedioic acid (93.5 mg, 183 µmol) in CH2Cl2 (3.7 mL) was added oxalyl chloride (7.3 mL, 84 µmol) at r.t. After 12 h, the reaction mixture was concentrated under reduced pressure. Then, the resulting residue was added to a mixture that was composed of 15b (137 mg, 457 µmol), pyridine (3.7 mL) and CH2Cl2 (7.3 mL) at r.t. After stirring for 12 h, the reaction was quenched by the addition of 1.5 mL of H2O. The mixture was then extracted with CHCl3 (100 mL). The organic layer was washed with H2O (5mL × 2) and brine (5mL), and concentrated under reduced pressure to yield a residue. The residue was purified by column chromatography [silica, CHCl3-EtOAc-MeOH (10/10/1 to 5/5/1, v/v/v)] to give 1b (18.4 mg, 9.4%).
13 All new compounds gave satisfactory analytical and spectral data. Compound 1a: colorless solid, [α]D
29 -18.76 (c 0.50, MeOH). 1H NMR (500 MHz, CDCl3): δ = 6.28 (2 H, d, J = 7.7 Hz), 5.79 (2 H, dtd, J = 15.3, 6.7, 1 Hz), 5.53 (2 H, ddt, J = 15.3, 6.4, 1 Hz), 4.32 (2 H, br s), 3.95 (2 H, br d, J = 11.9 Hz), 3.91 (2 H, m), 3.71 (2 H, m), 2.85 (4 H, br s), 2.23 (4 H, t, J = 7.4 Hz), 2.06 (4 H, dt, J = 7.5, 6.7 Hz), 1.64 (4 H, tt, J = 7.4, 7.4 Hz), 1.38 (4 H, tt, J = 7.4, 7.4 Hz), 1.25-1.30 (28 H, m), 0.89 (6 H, t, J = 7.0 Hz) ppm. 13C NMR (125 MHz, CDCl3): δ = 174.0, 136.4, 128.8, 74.7, 62.5, 54.5, 36.8, 32.2, 31.4, 29.3, 29.2, 29.2, 29.2, 29.2, 28.8, 25.7, 22.5, 14.0 ppm. LRMS (ESI, m/z): 647 (M + Na). Compound 1b: colorless amorphous solid, 1H NMR (500 MHz, CDCl3): δ = 6.32 (2 H, m), 5.76 (2 H, dt, J = 15.3, 6.7 Hz), 5.50 (2 H, dd, J = 15.3, 6.8 Hz), 4.27 (2 H, m), 3.90 (2 H, m), 3.85 (2 H, m), 3.67 (2 H, m), 2.84 (4 H, br s), 2.25 (4 H, t, J = 7.3 Hz), 2.05 (4 H, m), 1.62 (4 H, m), 1.25-1.45 (96 H, m), 0.86 (6 H, t, J = 7.0 Hz) ppm. LRMS (ESI, m/z): 1097 (M + Na).
14
Regioselective Benzoylation of 1a: Compound 1a (170 mg, 0.272 mmol) and DMAP (33 mg, 0.272 mmol) were dissolved in pyridine (3 mL) and stirred at -40 °C for 1 h in an atmosphere of nitrogen gas. After addition of benzoyl chloride (0.070 mL, 0.598 mmol), the reaction mixture was then stirred at -40 °C for 4 h. A sat. NH4Cl aqueous solution was added to quench the reaction, and the mixture was then extracted with CHCl3 (15 mL × 4). The organic layer was washed with brine (20 mL), dried over anhyd Na2SO4, and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography [silica, n-hexane/EtOAc/CHCl3 (6:6:1)] to give 16a (158 mg, 70%).