Reaction Steps
Butyllithium (3.63 ml, 6.17 mmol, 1.7 M in pentane) was added dropwise to a solution of tert-butylhydroperoxide (2.55 ml, 8.42 mmol, 3.3 M in toluene) in freshly distilled THF (80 ml) at −78° C. under argon. A solution of Cbz-Leu-Phe-VS-Ph (3.00 g, 5.61 mmol) in dry THF (30 ml) was added dropwise. The reaction was continued to stir at −20° C. for 45 minutes (TLC Hex/EtOAc 1:1). The reaction was quenched with saturated aqueous ammonium chloride (50 ml) and allowed to warm to room temperature. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate (3×30 ml). The extracts were then washed with aqueous sodium sulfite (10%, 3×20 ml). The combined organic layers were dried (MgSO4) and evaporated to give Cbz-Leu-Phe-AS-Ph as a white powder, yield 63%. 1H-NMR (CDCl3) δ 0.8-0.9 (2d, 6H, 2×Leu-CH3), 1.4-1.6 (m, 2H, Leu-CH2), 3.8 (s, 2H, CH2-Phe), 3.9 (d, 2H, CH2—SO2), 4.1 (m, 1H, α-H), 4.8 (t, 1H, CH═), 4.9-5.0 (b, 1H, NH), 5.1 (m, 2H, Cbz), 7.1-7.4 (m, 10H, 2×Ph), 7.5-7.7 (m, 5H, SO2-Ph), 8.4 (b, 1H, NH). 13C NMR (400 MHz, CDCl3) δ 172.1, 156.3, 144.4, 140.8, 135.7, 134.2, 133.6, 131.2, 129.5, 129.4×2, 129.3, 128.8×2, 128.7, 128.6, 128.4, 128.3, 127.8, 127.3, 126.9, 106.3, 67.6, 56.0, 55.6, 41.7, 40.4, 22.1, 21.0, 18.4. MS (FAB+) m/z 535 (M+1, 100%). Anal. Calcd. for C30H34N2O5S: C, 67.39; H, 6.56; N, 5.43. Found: C, 67.41; H, 6.56; N, 5.43.
