Reaction Steps
To a solution of (3S,6S,7R,8R)-8-(2-tert-butoxy-2-oxoethyl)-3-(tert-butoxycarbonylamino)-6-methyl-4,9-dioxo-1,5-dioxonan-7-yl isobutyrate (130 mg, 0.267 mmol) in EtOAc (3 mL) was added 1M HCl in EtOAc and the solution was stirred at room temperature (about 22° C.) for 6 h. The solvent was evaporated and the residue was dissolved in CH2Cl2 (1.5 mL). To this solution was added 3-hydroxy-4-methoxypicolinic acid (58 mg, 0.345 mmol), HATU (139 mg, 0.367 mmol) and N-methylmorpholine (120 mL, 1.09 mmol), sequentially. The reaction was allowed to stir at ambient temperature for 12 h and then loaded directly onto a SiO2 column and purified by flash chromatography (hexanes/EtOAc gradient) to give the title compound (62 mg, 43%) as a white solid: mp 192-194° C.; 1H NMR (400 MHz, CDCl3) δ 11.79 (d, J=0.5 Hz, 1H), 8.63 (d, J=8.3 Hz, 1H), 8.01 (d, J=5.2 Hz, 1H), 6.89 (d, J=5.1 Hz, 1H), 5.45 (s, 1H), 5.21 (dd, J=15.5, 8.3 Hz, 1H), 5.12-5.01 (m, 1H), 5.01-4.87 (m, 1H), 3.95 (s, 3H), 3.80 (d, J=25.0 Hz, 1H), 2.98 (ddd, J=11.8, 9.9, 3.2 Hz, 1H), 2.86-2.74 (m, 1H), 2.62 (dt, J=14.0, 7.0 Hz, 1H), 2.35-2.23 (m, 1H), 1.41 (s, 9H), 1.30 (dd, J=6.2, 2.4 Hz, 3H), 1.22 (dd, J=7.0, 1.6 Hz, 6H); 13C NMR (101 MHz, CDCl3) δ 175.50, 172.00, 170.26, 169.90, 169.01, 155.45, 148.86, 140.73, 129.97, 109.74, 81.74, 74.79, 74.07, 65.03, 56.13, 49.80, 45.81, 34.93, 34.02, 27.97, 18.96, 18.84, 17.79; ESIMS m/z 539 ([M+H]+).
