Reaction Steps
compound SP303r2. To a solution of Trp-NHPh (202 mg, 0.723 mmol) in CH2C12/DMF (3 mL, 1/1) at 0° C. were successively added N-Boc-Tyr(Bn)-Ala-OH (320 mg, 0.723 mmol), EDC (153.6 mg, 0.8 mmol) and HOBt (108 mg, 0.8 mmol). The resulting mixture was allowed to warm up to room temperature overnight. The solvent was evaporated and the crude was triturated with water. After filtration, the solid was collected and purified by precipitation in CH2Cl2/MeOH to give a white amorphous solid (160.3 mg, 31%). 1H NMR (300 MHz, DMSO-d6) δ 1.22 (d, J=7 Hz, 3H, CH3), 1.28 (s, 9H, (CH3)3), 2.63 (m, 1H, CH2), 2.89 (m, 1H, CH2), 3.06 (dd, J=14.5 Hz, 7.5 Hz, 1H, CH2), 3.2 (dd, J=14.5 Hz, 6.1 Hz, 1H, CH2), 4.1 (m, 1H, CHα), 4.34 (m, 1H, CHα), 4.69 (m, 1H, CHα), 5.02 (s, 2H, CH2 (Bn)), 6.88 (d, J=8.5 Hz, 2 aromatic H Tyr), 6.94 (m, 2 aromatic H Trp), 7.03 (t, J=7.4 Hz, 2 aromatic H Trp), 7.16 (m, 3 aromatic H), 7.25-7.42 (m, 8H), 7.58 (m, 3H), 8.02 (d, J=7.2 Hz, 1H), 8.18 (d, J=7.6 Hz, 1H), 10 (s, 1H, NH), 10.8 (s, 1H, NH). 13C NMR (75 MHz, DMSO-d6) δ 18.2 (CH3), 27.7 (CH2 Trp), 28.1 ((CH3)3), 36.3 (CH2 Tyr), 48.1, 54.2, 55.7 (CHα Ala, Tyr, Trp), 69 (CH2 (Bn)), 78 (C(CH3)3), 109.5, 111.2, 114.2, 118.2, 118.4, 119.4, 120.8, 123.3, 123.5, 127.3, 127.5, 127.7, 128.3, 128.6, 130.1, 130.3, 135.9, 137.2, 138.8 (25 aromatic C), 155.2, 156.8 (Car-O, CO carbamate), 170, 171.5, 172.1 (3 CO amide). Anal. Calcd. for C41H45N5O6, 0.5H2O: C, 69.08; H, 6.5; N, 9.82. Found: C, 68.82; H, 6.34; N, 9.79.
