Compound 7

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InChIKey RKXUHIOQDOWAQJ-RUFXTULGSA-N

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

In a polypropylene vial, the enoate mixture 28 (ca. 0.0045 mmol) was dissolved in THF (2.0 mL). The resulting solution was cooled in an ice water bath and HF·pyridine (70% HF, 500 μL) was added dropwise over 30 s. The mixture was stirred at 0 °C for 5 min and was then warmed to ambient temperature. After 74 h, the reaction was quenched by its dropwise addition to stirred, saturated aqueous NaHCO₃ (20 mL). This mixture was extracted with EtOAc (3 × 20 mL) and the combined organic phase was washed with 30 mL 0.2 N HCl. The acidic aqueous phase was extracted with additional EtOAc (2 × 20 mL). The combined organic phase was dried over Na₂SO₄, filtered, and concentrated to afford a crude residue that was used immediately in the following step. The crude residue from the previous step was dissolved in a solution of PPTS (0.05 M in 20% H₂O:THF, 600 μL, 0.03 mmol) at ambient temperature. After 39 h, the reaction was then diluted with Et₂O (500 μL), H₂O (500 μL), and brine (500 μL). The organic an aqueous phases were separated, and the aqueous phase was extracted with Et₂O (5 × 1 mL). The combined organic layer was dried over MgSO₄, filtered, and concentrated to afford a crude residue that was partially purified by flash chromatography (60% EtOAc in hexanes) to afford a mixture of enoate analogues that was separated by reverse phase HPLC (C18, 10 micron, 10 × 250 mm, 65 → 100 % MeCN in H₂O) to afford 1.3 mg Z-enoate analogue 7 (29% over 3 steps) and 1.2 mg E-enoate analogue S7 (27% over 3 steps) as amorphous white solids. Compound purity was established by TLC (one spot) and ¹H-NMR analysis. ¹H NMR (CDCl₃, 500 MHz): δ = 5.98 (d, 1H, J = 1.8 Hz, C34), 5.74 (d, 1H, J = 15.7 Hz, C17), 5.68 (bs, 1H, C30), 5.32 (m, 1H, C25), 5.32 (dd, 1H, J = 8.4, 15.7 Hz), 5.16 (s, 1H, C19-OH), 5.14 (m, 1H, C7), 5.13 (s, 1H, C20), 4.24 (d, 1H, J = 12.0 Hz, C3-OH), 4.23 (m, 1H, C5), 4.17 (m, 1H, C3), 4.04 (tt, 1H, J = 2.2, 11.3 Hz, C23), 3.98 (ddd, 1H, J = 2.3, 8.6, 11.1 Hz, C15), 3.84 (m, 1H, C26), 3.78 (m, 1H, C13), 3.72-3.61 (m, 3H, C14, C22, C26), 3.70 (s, 3H, -CO₂Me), 3.68 (s, 3H, -CO₂Me), 2.52-2.42 (m, 3H, C2, C2, C19-OH), 2.31 (m, 2H, C40, C40), 2.21 (m, 1H, C12), 2.14-1.96 (m, 6H, C4, C10, C12, C22, C24, C26-OH), 2.05 (s, 3H, C7-OAc), 1.91 (m, 1H, C14), 1.78 (m, 2H, C6, C24), 1.67 (d, 1H, J = 15.4 Hz, C10), 1.64-1.53 (m, 3H, C4, C41, C41), 1.48 (q, 1H, J = 12.0 Hz, C6), 1.27 (m, 8H, C42-C45), 1.15 (s, 3H, -CH₃), 1.00 (s, 6H, -CH₃, -CH₃), 0.95 (s, 3H, -CH₃), 0.87 (t, 3H, J = 7.1 Hz, C46) ppm. ¹³C NMR (CDCl₃, 100 MHz): δ = 172.5, 172.4, 171.1, 167.1, 166.8, 156.5, 151.9, 139.1, 129.7, 119.9, 114.6, 102.0, 99.0, 79.3, 74.4, 73.0, 71.7, 71.6, 68.5, 65.9, 65.6, 64.8, 51.3, 51.2, 45.0, 44.2, 42.4, 42.1, 41.1, 39.8, 36.4, 35.9, 34.8, 33.4, 31.8, 31.2, 29.2, 29.0, 24.8, 24.7, 22.7, 21.3, 21.2, 19.9, 17.0, 14.2 ppm. IR: 3466, 3350, 2930, 1738, 1722, 1715, 1660, 1435, 1408, 1366, 1247, 1157, 1079, 1030, 1003, 984, 859, 811 cm⁻¹. HRMS (TOF MS ES+): Calculated for C₄₆H₇₀O₁₇Na⁺: 917.4505; Found: 917.4523. [α]_D^23.2 = + 42.6 ± 1.1° (c = 0.23, CH₂Cl₂). R_f = 0.29 (50% EtOAc in petroleum ether), one purple spot, p-anisaldehyde stain.