反应详情

A mixture of (1R,10S,11S,16S)-3-methoxy-11,15,15-trimethyl-8,8-dioxo-8λ6-thiatetracyclo[8.8.0.02,7.011,16]octadeca-2,4,6-triene-5-carboxylic acid (61) (0.20 g, 0.49 mmol), HATU (0.37 g, 0.98 mmol), N-methylmorpholine (0.10 mL, 1.5 mmol) and 1-methylpiperazine (0.15 mL, 1.5 mmol) in THF (10 mL) and DMF (2.0 mL) was stirred at room temperature for 18 h. The THF was evaporated under reduced pressure, the residue was quenched with water and the resulting solid was collected by filtration. The crude product was purified by flash column chromatography on silica gel (CH2Cl2/MeOH, 10:1) to give (1R,10R,11S,16S)-3-hydroxy-1,11,15,15-tetramethyl-5-[(4-methyl piperazin-1-yl)-carbonyl]-8λ6-thiatetracyclo[8.8.0.02,7.011,16]octadeca-2,4,6-triene-8,8-dione (89) (0.13 g, 54%) as a white solid. 1H NMR (CDCl3): δ 9.55 (s, 1H), 7.23 (d, 1H), 7.07 (d, 1H), 3.84 (m, 2H), 3.49 (m, 2H), 3.18 (m, 3H), 2.52 (m, 2H), 2.38 (m, 2H), 2.33 (s, 3H), 2.15 (d, 1H), 1.78-1.32 (m, 6H), 1.28 (s, 3H), 1.24-1.05 (m, 2H), 0.98 (m, 1H), 0.90 (s, 6H), 0.86 (m, 1H), 0.82 (s, 3H). MS m/z 489 (C27H40N2O4S+H+).

1. customThe THF was evaporated under reduced pressure
2. customthe residue was quenched with water
3. filtrationthe resulting solid was collected by filtration
4. customThe crude product was purified by flash column chromatography on silica gel (CH2Cl2/MeOH, 10:1)