Reaction Steps
N-tert-butoxycarbonyl O-allyl L-seryl L-valyl L-valine methyl ester (8) (10.21 g, 22.31 mmol) was dissolved in THF (170 mL). The solution was cooled to 0° C. (icebath). LiOH monohydrate (1.03 g, 24.6 mmol) was dissolved in de-ionized water (85 mL) and the solution cooled to 0° C. The solution was then added dropwise to the solution of 8 over 20 min. The reaction mixture was stirred for an additional 2 h 40 min at 0° C. Solid NaHCO3 (3.75 g, 44.6 mmol) was added and the mixture stirred for 5 min before the THF was evaporated. The solution was diluted with water (170 mL), washed with Et2O (2×170 mL), acidified to pH 2 by addition of 2 M aqueous H2SO4 and extracted with EtOAc (3×250 mL). The combined organic fractions were dried with anhydrous MgSO4 and the solvent evaporated affording the title compound as a white solid (7.00 g, 71%); δH (300 MHz; d6-DMSO) 12.53 (1H, br s, COOH), 8.00 (1H, d, J 8, NH (Valx)), 7.62 (1H, d, J 9, NH(Valy)), 7.02 (1H, d, J 8, NH (Ser(All))), 5.84 (1H, ddt, J 5, 10 and 17, CH═CH2), 5.23 (1H, ddt, J 1, 3 and 17, CH═CHH)), 5.12 (1H, ddt, J 1, 3 and 10, CH═CHH), 4.34 (1H, dd, J 7 and 9, CαH(Valy)), 4.21-4.15 (1H, m, CαH(Ser(All))), 4.10 (1H, dd, J 6 and 8, CαH(Valx)), 3.92 (2H, dt, J 1 and 5, CH2CH═CH2), 3.59-3.45 (2H, m, CH2), 2.06-1.91 (2H, m, CH(CH3)2), 1.38 (9H, s, (CH3)3), 0.90-0.80 (12H, m, CH3); δC (75 MHz; d6-DMSO) 172.6, 170.9, 169.5, 155.1, 134.9, 116.3, 78.2, 71.0, 69.5, 57.2, 56.9, 54.6, 31.1, 29.6, 28.1, 19.0, 19.0, 17.9, 17.7; m/z (ESI) 466.2518 ([M+Na]+; C21H37N3O7Na requires 466.2529)
