Compound 5

View in PubChem | MDL Molfile | ChemDraw

InChIKey PJNIHQVUSONDAR-KTRVGUEHSA-N

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

In a 15 mL polypropylene vial, enoate mixture 26 (8.1 mg, ca 0.0069 mmol) was dissolved in THF (6.2 mL) under N₂ atmosphere. This solution was cooled in a CO₂/acetone bath for 10 min, at which time 70% HF·pyridine (1.55 mL) was added dropwise over 1 min. The reaction vessel was allowed to stir at -78°C for 10 more min, at which time the reaction vessel was removed from the cold bath and allowed to warm to ambient temperature. After stirring 90 h, the reaction mixture was quenched into saturated aqueous NaHCO₃ (50 mL). The resulting mixture was diluted with water (15 mL) and Et₂O (30 mL). The layers were separated, and the aqueous layer was extracted with EtOAc (3 × 25 mL). The combined organic phase was dried over Na₂SO₄, filtered, and concentrated. The resulting oil was purified via silica gel column chromatography (45→50% EtOAc:Pentane) to afford 4.5 mg (79%) as a mixture of enoate analogues 5 (Z-enoate) and C13-C30 geometric isomer S5 (E-enoate). This mixture was separated via preparative reverse-phase C18 chromatography (65% MeCN→100% MeCN in H₂O over 30 minutes) to afford 2.2 mg analogue 5 (38%) and 1.1 mg C13-C30 geometric isomer S5 (19%). ¹H NMR (CDCl₃, 500 MHz): δ 5.99 (d, J = 1.7 Hz, 1H, C27), 5.74 (d, J = 15.9 Hz, 1H, C17), 5.67 (s, 1H, C30), 5.35 (m, 1H, C25), 5.33 (dd, J = 8.3, 15.9 Hz, 1H, C16), 5.18 (s, 1H, C19-OH), 5.13 (s, 1H, C20), 4.96 (d, J = 11.7 Hz, 1H, C3-OH), 4.22 (m, 1H, C3), 4.06 (tt, J = 2.2, 11.2 Hz, 1H, C23), 3.97 (ddd, J = 2.2, 8.3, 10.7 Hz, 1H, C15), 3.84 (dt, J = 3.9, 12.0 Hz, 1H, C26), 3.68-3.75 (m, 1H, C22), 3.70 (s, 3H, -OMe), 3.68 (s, 3H, -OMe), 3.60-3.66 (m, 2H, C14, C26), 3.55 (ddd, J = 2.7, 6.4, 10.7 Hz, 1H, C11), 3.49 (bt, J = 11.2 Hz, 1H, C5), 3.13 (dd, J = 1.7, 11.5 Hz, 1H, C9), 2.40-2.49 (m, 2H, C2, C2), 2.25-2.35 (m, 2H, C31), 2.08-2.23 (m, 2H, C12, C12), 1.92-2.08 (m, 4H, C4, C22, C24, C26-OH), 1.89 (bt, J = 12.7 Hz, 1H, C14), 1.79 (ddd, J = 2.7, 11.7, 13.7 Hz, 1H, C24), 1.70 (ddd, J = 6.6, 11.7, 15.4 Hz, 1H, C10), 1.62 (m, 2H, C32), 1.41-1.53 (m, 3H, C4, C6, C10), 1.21-1.38 (m, 11H, C6, C7, C7, C33-C36), 1.15 (s, 3H, C28), 1.01 (s, 3H, C29), 0.88 (t, J = 6.8 Hz, 3H, C37), 0.86 (s, 3H, C(8)(CH₃)₂), 0.81 (s, 3H, C(8)(CH₃)), ppm. ¹³C NMR (CDCl₃, 125 MHz): δ 172.5, 172.3, 167.2, 166.9, 157.0, 152.0, 138.6, 130.0, 119.9, 114.4, 99.0, 86.2, 79.0, 76.2, 74.4, 71.6, 68.8, 65.9, 64.6, 51.2, 51.2, 45.0, 44.2, 43.0, 40.3, 39.0, 37.0, 36.6, 36.0, 34.8, 32.4, 31.8, 31.2, 29.2, 29.0, 29.0, 27.8, 24.8, 24.7, 22.7, 19.9, 19.4, 14.2 ppm. IR (film) 3458, 3338, 2930, 2851, 1721, 1658, 1434, 1407, 1378, 1282, 1258, 1226, 1160, 1099, 1084, 1046, 1004, 877, 807 cm⁻¹. HRMS (TOF MS ES+): Calculated for C₄₄H₆₈O₁₄Na⁺: 843.4507; Found: 843.4501. [α]_D^23.7 = 21.47° (c = 0.22, CHCl₃). R_f = 0.44 (60%% EtOAc , 40% Petroleum ether) – one black spot (p-anisaldehyde stain).