Reaction Steps
The methyl ester 18 (2.2 g, 4.26 mmol) was dissolved in MeOH (30 mL). Sodium hydroxide (340 mg, 8.5 mmol) was dissolved in water (7 mL) and added to the ester solution. The reaction mixture was stirred at 70° C. for 15 min. The methanol was then removed under vacuum and water (20 mL) was added. The aqueous solution was allowed to return to room temperature and a 5% aqueous citric acid solution was added to adjust the pH to <4. The precipitate was extracted with EtOAc (100 mL). The organic layer was washed with brine (30 mL) and dried over MgSO4. The solvent was removed under vacuum, then diethylether (50 mL) was added to the residue and removed under vacuum, then dried under vacuum to yield the pure 19 as white foam 2.10 g (98%). 1H NMR (d6-DMSO) as a mixture of 4/5 of diastereoisomers δ 7.10 (2H, s×2), 6.90-6.84 (2H, s×2), 5.84-5.68 (4H, m), 5.45-4.91 (6H, m), 4.72-4.30 (4H, m), 4.09-3.93 (4H, m), 3.91-3.75 (8H, m), 3.60-3.44 (4H, m), 3.44-3.22 (8H, m), 2.46-2.33 (4H, m), 2.20-1.76 (14H, m), 1.76-1.31 (12H, m). 13C NMR (d6-DMSO) δ 173.9, 173.9, 171.9, 166.1, 166.0, 149.6, 148.4, 148.3, 132.6, 116.5, 114.4, 110.5, 110.3, 99.2, 67.5, 67.4, 65.6, 65.5, 62.8, 59.4, 55.7, 45.9, 30.5, 30.2, 29.8, 29.7, 28.4, 28.3, 24.9, 24.8, 23.9, 23.8, 22.9, 22.7; MS (ES+) m/z (relative intensity) 519.2 ([M+H]+, 100). This compound was proved optically pure at C11a by reesterification (EDCI, HOBt, then MeOH), THP removal (AcOH/THF/H2O) and chiral HPLC, as in Tercel et al., J. Med. Chem., 2003, 46, 2132-2151).
