Synthesis of (-)-9 Rocaglate Derivative

A round bottom flask was charged with (-)-rocaglaic acid (27.0 mg, 0.06 mmol), CH₂Cl₂(4 mL), EDCI (16 mg, 0.08 mmol), HOBt (11 mg, 0.07 mmol), methoxylamine hydrochloride (24 mg, 0.28 mmol), and triethylamine (39 uL, 0.28 mmol), and was stirred at room temperature for 12 h. The reaction was quenched with 1M HCl, concentrated, and purified by flash chromatography (gradient elution 50% to 100% ethyl acetate in hexanes) to afford a (-)-9 as white solid (14 mg, 49%). ¹H NMR (500 MHz, CD₃ OD) δ 7.15 (d, J = 9.0 Hz, 2H), 7.09 – 6.99 (m, 3H), 6.94 (d, J = 6.9 Hz, 2H), 6.64 (d, J= 9.0 Hz, 2H), 6.32 (d, J = 1.9 Hz, 1H), 6.21 (d, J= 1.9 Hz, 1H), 4.79 (d, J = 6.2 Hz, 1H), 4.32 (d, J= 14.2 Hz, 1H), 3.87 (s, 1H), 3.85 (s, 1H), 3.72 (dd, J= 14.2, 6.2 Hz, 1H), 3.69 (s, 1H), 3.60 (s, 1H); HRMS calcd for [C₂₈H₂₉NO₈Na]⁺ requires m/z 530.1791; found 530.1772 (ES+).; [a]_D²⁰ = -38.4 (c0.5, CH₃OH, at >98% ee).