Table 1.
Summary of yields and epimerization rates for various peptide coupling conditions
| Fmoc-Ser(R)-OH, where R = | |||||||
|---|---|---|---|---|---|---|---|
| # | Coupling Conditionsa | Trt | Ac3GalNAcα | Ac4Galβ1-3Ac2GalNAcα | Ac3GlcNAcα | Ac3GlcNAcβ | |
| 1 | AAs: 2.5 eq | Yields (%)b | 75.1 | 69.1 | 83.9 | 100 | 69.0 |
| HATU/HOAt: 1.1/1.1 eq | Epimerization (D/(D+L) %)b | 0.8 | 5.1 | 4.3 | 7.7 | 8.1 | |
| NMM 2.2 eq | |||||||
| 0/3 h in DMF57 | |||||||
| 2 | AAs: 1.5 eq | Yields (%)b | 81.0 | 74.6 | 96.7 | 89.9 | 92.0 |
| HATU/HOAt: 1.2/1.2 eq | Epimerization (D/(D+L) %)b | 2.2 | 11.4 | 21.2 | 15.0 | 20.0 | |
| NMM: 2:4 eq | |||||||
| 0/8 h in DMF58 | |||||||
| 3 | AAs: 3.3 eq | Yields (%)b | 98.9 | 99.8 | 99.6 | 100 | 96.8 |
| HATU/HOAt: 3.65/3.7 eq | Epimerization (D/(D+L) %)b | 0.2 | 0.8 | 2.5 | 1.8 | 3.4 | |
| DIPEA: 7.22 eq | |||||||
| 0/12 h in DMF59 | |||||||
| 4 | AAs: 4.4 eq | Yields (%)b | 63.4 | 99.4 | 83.0 | 100 | 1.9 |
| HATU/HOAt: 4.4/0 eq | Epimerization (D/(D+L) %)b | 37.6 | 69.8 | 65.6 | 72.5 | 52.0 | |
| NMM: 8.8 eq | |||||||
| 3/12 h in NMP59 | |||||||
| 5 | AAs: 5 eq | Yields (%)b | 98.4 | 99.4 | 98.8 | 99.5 | 95.2 |
| HATU/HOAt: 6.25/6.25 eq | Epimerization (D/(D+L) %)b | 2.9 | 5.2 | 6.5 | 8.1 | 9.7 | |
| NMM: 12.5 eq | |||||||
| 0/6 h in NMP59 | |||||||
| 6 | AAs: 2 eq | Yields (%)b | 99.5 | 96.7 | 99.4 | 100 | 94.9 |
| HBTU/HOBt: 4.5/4.5 eq | Epimerization (D/(D+L) %)b | 0.4 | 7.9 | 7.4 | 11.5 | 7.3 | |
| DIPEA: 9 eq | |||||||
| 0/1 h in NMP60 | |||||||
| 7 | AAs: 3 eq: | Yields (%)b | 99.5 | 99.7 | 97.8 | 90.5 | 98.6 |
| DCC/HOBt: 18/18 eq | Epimerization (D/(D+L) %)b | 0.1 | 1.9 | 2.4 | 1.7 | 2.8 | |
| 1/64 h in NMP61 | |||||||
| 8 | AAs: 2 eq | Yields (%)b | 99.5 | 87.1 | 99.7 | 86.0 | 90.3 |
| PyBOP/HOBt: 2/2 eq | Epimerization (D/(D+L) %)b | 1.2 | 10.1 | 11.7 | 8.8 | 5.7 | |
| DIPEA: 4 eq | |||||||
| 0/24 h in DMF62 | |||||||
| 9 | AAs: 1.5 eq | Yields (%)b | 95.8 | 88.1 | 98.0 | 85.6 | 86.0 |
| HBTU/HOBt: 1.5/1.5 eq | Epimerization (D/(D+L) %)b | 0.7 | 2.1 | 3.7 | 4.4 | 3.9 | |
| DIPEA: 1.5 eq | |||||||
| 0/0.33 h in DMF63 | |||||||
| 10 | AAs: 5 eq | Yields (%)b | 99.6 | 99.9 | 99.5 | 100.0 | 96.7 |
| HBTU/HOBt: 5/7.5 eq | Epimerization (D/(D+L) %)b | 0.8 | 5.2 | 7.8 | 13.3 | 8.6 | |
| NMM: 10 eq | |||||||
| 0/5 h in DMF64 | |||||||
| 11 | AAs: 5 eq | Yields (%)b | 99.6 | 99.7 | 99.0 | 100 | 98.2 |
| DIC/HOBt: 10/10 | Epimerization (D/(D+L) %)b | 0.5 | 2.9 | 2.9 | 5.5 | 8.0 | |
| 0.5/0.5 h in DMF65 | |||||||
| 12 | AAs: 2.5 eq | Yields (%)b | 97.1 | 98.4 | 99.7 | 90.7 | 96.2 |
| BOP/HOBt: 2.5/2.5 eq | Epimerization (D/(D+L) %)b | 0.1 | 3.0 | 2.8 | 3.9 | 2.6 | |
| DIPEA: 2.5 eq | |||||||
| 0/4 h in DMF66 | |||||||
| 13 | AAs: 2.0 eq | Yields (%)b | 98.7 | 99.1 | 99.5 | 100 | 98.9 |
| HATU/HOAt: 2.0/2.0 eq | Epimerization (D/(D+L) %)b | 0.2 | 1.1 | 0.3 | 1.6 | 0.6 | |
| TMP: 2.0 eq | |||||||
| 0/2 h in DMF | |||||||
a
Glyco-amino acids were coupled to Pro-Gly-Hex resin. For the coupling times, the first number refers to the pre-incubation time and the second number refers to the reaction time (e.g. 3/12 h = 3 h pre-incubation followed by 12 h reaction time).
b
All yield and epimerization data have an error of less than 0.3%.