Synthesis of H-Leu-Ala-Phe-OH in solvent mixtures and neat solvents reported by North and co-workers34a.
| Solvent | Yieldb (mg g−1) | Purity (RP-HPLC) |
|---|---|---|
| PC | 8 | 3.1% |
| EtOAc | 292 | 96.9% |
| TMO | 0 | — |
| EtOAc/PC (9 : 1) | 307 | 95.2% |
| TMO/PC (9 : 1) | 124 | 100% |
| TMO/PC (3 : 7) | 132 | 96.7% |
| TMO/PC (2 : 3)c | 200 | 94.2% |
a
Fmoc-removal was carried out with 20% piperidine in solvent (v/v) for 20 min. Couplings were performed for 1 h at room temperature. Fmoc-amino acid (3.0 equiv.), HBTU (3.0 equiv.), HOBt (3.0 equiv.) and DIPEA (6.0 equiv.) were dissolved at a 0.1 M concentration and stirred for 20 min before adding this mixture to the resin. For the synthesis in PC, after the final Fmoc-removal, the resin was also washed with EtOAc (5 mL).
b
Yields are given in mg g−1 of resin as the starting loading for the Merrifield resin was imprecise (0.4–0.8 mmol g−1).
c
Immiscible in this ratio.