Table 1.
PF1022A solid phase-synthesis—optimization of coupling-steps 1–4
| Step (entry) | Building block (3.0 equiv) | Product (bond formed) | No. of couplings | Conditions (equiv) | Yield (%) |
|---|---|---|---|---|---|
| 1a | THP-PhLac | 19 (ester) | 3 | DIC (3.0), DMAP (0.1) | 62a |
| 1b | 2 | DIC (3.0), DMAP (3.0), HOBt (3.0) | 92a | ||
| 1c | 2 | EDCI (3.0), DMAP (0.1) | 17a | ||
| 1d | 3 | HATU (2.0), DIEA (3.0) | 36a | ||
| 2a | Fmoc-NMe-Leu | 20 (ester) | 3 | DIC (3.0), DMAP (0.1) | 91b |
| 2b | 2 | DIC (3.0), DMAP (3.0), HOBt (3.0) | 93b | ||
| 2c | 2 | EDCI (3.0), DMAP (0.1) | 44b | ||
| 3a | THP-Lac | 21 (amide) | 2 | HATU (2.0), DIEA (3.0) | 77a |
| 3b | 2 | DIC (3.0), DMAP (0.1) | 54a | ||
| 3c | 2 | DIC (3.0), DMAP (3.0), HOBt (3.0) | 48a | ||
| 3d | 2 | EDCI (3.0), DMAP (0.1) | 19a | ||
| 3e | 1 | 15 acid chloride (3.0), DMAP (1.0) | 34a | ||
| 4a | Fmoc-NMe-Leu | 22 (ester) | 2 | DIC (3.0), DMAP (0.1) | 51b |
| 4b | 2 | DIC (3.0), DMAP (3.0), HOBt (3.0) | 77b | ||
| 4c | 1 | Acid chloride (3.0), DMAP (1.0) | 5b | ||
| 4d | 1 | (Fmoc-NMe-Leu)2O (3.0 equiv), DMAP (3.0 equiv) | 38b | ||
| 4e | 2 | TPP (3.0 equiv), DEAD (3.0 equiv) | 51b |
a
Gravimetric determination of the product after deprotection and cleavage from the resin.
b
UV-determination after Fmoc removal. Yields calculated on a loading of 1.07 mmol/g resin. THF was used as solvent in all experiments.