Chem. J. Chinese Universities ›› 2020, Vol. 41 ›› Issue (7): 1559.doi: 10.7503/cjcu20200032
• Organic Chemistry • Previous Articles Next Articles
LI Shijie,YANG Yang,CUI Yingying,SU Xianbin()
Received:
2020-01-14
Online:
2020-07-10
Published:
2020-05-09
Contact:
SU Xianbin
E-mail:davidsu@njtech.edu.cn
Supported by:
CLC Number:
TrendMD:
LI Shijie,YANG Yang,CUI Yingying,SU Xianbin. High Efficient and Green Approach to the Synthesis of Leuprolide in Continuous-flow Microreactor†[J]. Chem. J. Chinese Universities, 2020, 41(7): 1559.
Compd. | 1H NMR, δ | ESI-MS, m/z |
---|---|---|
1 | 7.36—7.31(m, 5H, ArH), 5.21—5.07(m, 2H, CCH2O), 4.31(d, J=7.0 Hz, 1H, CH), 3.54— | 277.14[M+H]+ |
3.23(m, 4H, NCH2C), 2.36—1.88(m, 4H, CH2CH2), 1.05(t, J=8.4 Hz, 3H, CH3) | ||
2 | 4.10(t,J=7.8 Hz, 1H, NCHCO), 3.24—3.10(m, 4H, NCH2), 2.27—1.80(m, 4H, CH2CH2), | 143.22[M+H]+ |
1.05(t, J=7.3 Hz, 3H, CH3) | ||
3 | 7.38—7.33(m, 5H, ArH), 5.1(m, 2H, CH2O), 4.55—4.33(m, 2H, NCH), 3.71—3.24(m, | 633.54[M+H]+ |
6H, NCH2), 2.37—2.02(m, 4H, CH2CH2), 1.53(m, 2H, CH2), 1.5(s, 18H, CH3), 1.28— | ||
1.25(m, 2H, CH2), 1.09(t, J=7.2 Hz, 3H, CH3) | ||
17 | 2021.10[M+Na]+ | |
18 | 1865.09[M+H]+ | |
19 | 8.60—6.61(m, 23H, ArH, NHCO, Indole—H, Imidazole—H), 4.58—3.97(m, 9H, NCHCO), | 1209.63[M+H]+ |
3.66—3.45(m, 2H, OCH2), 3.18—2.71(m, 12H, NCH2), 2.28—1.33(m, 18H, CCH2, | ||
CCH), 1.03—0.75(m, 15H, CH3) |
Compd. | 1H NMR, δ | ESI-MS, m/z |
---|---|---|
1 | 7.36—7.31(m, 5H, ArH), 5.21—5.07(m, 2H, CCH2O), 4.31(d, J=7.0 Hz, 1H, CH), 3.54— | 277.14[M+H]+ |
3.23(m, 4H, NCH2C), 2.36—1.88(m, 4H, CH2CH2), 1.05(t, J=8.4 Hz, 3H, CH3) | ||
2 | 4.10(t,J=7.8 Hz, 1H, NCHCO), 3.24—3.10(m, 4H, NCH2), 2.27—1.80(m, 4H, CH2CH2), | 143.22[M+H]+ |
1.05(t, J=7.3 Hz, 3H, CH3) | ||
3 | 7.38—7.33(m, 5H, ArH), 5.1(m, 2H, CH2O), 4.55—4.33(m, 2H, NCH), 3.71—3.24(m, | 633.54[M+H]+ |
6H, NCH2), 2.37—2.02(m, 4H, CH2CH2), 1.53(m, 2H, CH2), 1.5(s, 18H, CH3), 1.28— | ||
1.25(m, 2H, CH2), 1.09(t, J=7.2 Hz, 3H, CH3) | ||
17 | 2021.10[M+Na]+ | |
18 | 1865.09[M+H]+ | |
19 | 8.60—6.61(m, 23H, ArH, NHCO, Indole—H, Imidazole—H), 4.58—3.97(m, 9H, NCHCO), | 1209.63[M+H]+ |
3.66—3.45(m, 2H, OCH2), 3.18—2.71(m, 12H, NCH2), 2.28—1.33(m, 18H, CCH2, | ||
CCH), 1.03—0.75(m, 15H, CH3) |
Entry | Amino acid | Efficiency of one wash in a reaction caldron(%) | Efficiency of one wash in a microchannel reactor(%) |
---|---|---|---|
1 | Z-Pro-OH | 100 | 100 |
2 | Z-Arg(Boc)2-OH | 32.5 | 56.4 |
3 | H-Arg(Boc)2-OH | 100 | 100 |
4 | Z-Leu-OH | 100 | 100 |
5 | Z-D-Leu-OH | 100 | 100 |
6 | Z-Tyr(tBu)-OH | 35 | 52.2 |
7 | H-Tyr(tBu)-OH | 100 | 100 |
8 | Z-Ser(tBu)-OH | 100 | 100 |
9 | Z-Trp(Boc)-OH | 20.2 | 31.6 |
10 | H-Trp(Boc)-OH | 100 | 100 |
11 | Z-His(Trt)-OH | 8.2 | 15.4 |
12 | H-His(Trt)-OH | 100 | 100 |
13 | Z-Pyr-OH | 100 | 100 |
Entry | Amino acid | Efficiency of one wash in a reaction caldron(%) | Efficiency of one wash in a microchannel reactor(%) |
---|---|---|---|
1 | Z-Pro-OH | 100 | 100 |
2 | Z-Arg(Boc)2-OH | 32.5 | 56.4 |
3 | H-Arg(Boc)2-OH | 100 | 100 |
4 | Z-Leu-OH | 100 | 100 |
5 | Z-D-Leu-OH | 100 | 100 |
6 | Z-Tyr(tBu)-OH | 35 | 52.2 |
7 | H-Tyr(tBu)-OH | 100 | 100 |
8 | Z-Ser(tBu)-OH | 100 | 100 |
9 | Z-Trp(Boc)-OH | 20.2 | 31.6 |
10 | H-Trp(Boc)-OH | 100 | 100 |
11 | Z-His(Trt)-OH | 8.2 | 15.4 |
12 | H-His(Trt)-OH | 100 | 100 |
13 | Z-Pyr-OH | 100 | 100 |
Step | Peptide | First-round efficiency(%) | Second-round efficiency(%) | Third-round efficiency(%) |
---|---|---|---|---|
1 | Z-Pro-NHEt | 100 | — | — |
2 | Z-Arg(Boc)2-Pro-NHEt | 97.3 | 100 | — |
3 | Z-Leu-Arg(Boc)2-Pro-NHEt | 91.4 | 100 | — |
4 | Z-D-Leu-Leu-Arg(Boc)2-Pro-NHEt | 89.7 | 100 | — |
5 | Z-Tyr(tBu)-D-Leu-Leu-Arg(Boc)2-Pro-NHEt | 94.1 | 100 | — |
6 | Z-Ser(tBu)-Tyr(tBu)-D-Leu-Leu-Arg(Boc)2-Pro-NHEt | 92.1 | 100 | — |
7 | Z-Trp(Boc)-Ser(tBu)-Tyr(tBu)-D-Leu-Leu-Arg(Boc)2-Pro-NHEt | 82.6 | 100 | — |
8 | Z-His(Trt)-Trp(Boc)-Ser(tBu)-Tyr(tBu)-D-Leu-Leu-Arg(Boc)2-Pro-NHEt | 33.5 | 76.2 | 100 |
9 | Z-Pyr-His(Trt)-Trp(Boc)-Ser(tBu)-Tyr(tBu)-D-Leu-Leu-Arg(Boc)2-Pro-NHEt | 79.6 | 100 | — |
Step | Peptide | First-round efficiency(%) | Second-round efficiency(%) | Third-round efficiency(%) |
---|---|---|---|---|
1 | Z-Pro-NHEt | 100 | — | — |
2 | Z-Arg(Boc)2-Pro-NHEt | 97.3 | 100 | — |
3 | Z-Leu-Arg(Boc)2-Pro-NHEt | 91.4 | 100 | — |
4 | Z-D-Leu-Leu-Arg(Boc)2-Pro-NHEt | 89.7 | 100 | — |
5 | Z-Tyr(tBu)-D-Leu-Leu-Arg(Boc)2-Pro-NHEt | 94.1 | 100 | — |
6 | Z-Ser(tBu)-Tyr(tBu)-D-Leu-Leu-Arg(Boc)2-Pro-NHEt | 92.1 | 100 | — |
7 | Z-Trp(Boc)-Ser(tBu)-Tyr(tBu)-D-Leu-Leu-Arg(Boc)2-Pro-NHEt | 82.6 | 100 | — |
8 | Z-His(Trt)-Trp(Boc)-Ser(tBu)-Tyr(tBu)-D-Leu-Leu-Arg(Boc)2-Pro-NHEt | 33.5 | 76.2 | 100 |
9 | Z-Pyr-His(Trt)-Trp(Boc)-Ser(tBu)-Tyr(tBu)-D-Leu-Leu-Arg(Boc)2-Pro-NHEt | 79.6 | 100 | — |
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