The Synthesis Of Cinaceptide
Cinaceptide is a synthetic 21-peptide used for the treatment of respiratory distress syndrome in preterm infants. Discovery Laboratories Inc is the original research company and was approved for marketing by the US FDA in March 2012.
The structure of Cinaceptide is as below:
Basic information
Chinese name: sinapritide
English name: Sinapultide
Company number: GT-F041
CAS Number: 138531-07-4
Sequence: H-Lys-Leu-Leu-Leu-Leu-Leu-Lys-Leu-Lys-Leu-Lys-OH
Formula: C126H238N26O22
Molecular weight: 2469.4
1. Preparation of Fmoc-Lys(Boc)-resin
1) Take 100g of 2-chloro-triphenyl chlororesin (0.5mmol/g resin, 50mmol), soak in 1000ml DMF for 30 minutes, make the resin fully swollen, add DIPEA 20ml, Fmoc-Lys(Boc)-OH 23.5g, 25°C for 65 minutes. Add 50ml of methanol and react at 25°C for 60 minutes.
2) Drain and dry, wash three times with DMF, methanol and DMF respectively, and drain dry.
2. Preparation of Fmoc-Leu-Lys(Boc)-resin
1) Add 1000ml of unhatting reagent, react at 21-23°C for 18 minutes, drain dry, wash with DMF, methanol and DMF three times each, and drain dry.
2) Take 53.0g Fmoc-Leu-OH, 57.0g HATU, and 20.5g HOAt, dissolve with 520ml of peptide reagent, add to the reaction vessel, and react at 0-5°C for 55 minutes.
3) Drain and wash three times with DMF, methanol and DMF respectively, and drain dry.
3. Preparation of Fmoc-Leu-Leu-Lys(Boc)-resin
1) Add 1000ml of unhatting reagent, react at 21-23°C for 18 minutes, drain dry, wash with DMF, methanol and DMF three times each, and drain dry.
2) Take 53.0g Fmoc-Leu-OH, 57.0g HATU, and 20.5g HOAt, dissolve with 520ml of peptide reagent, add to the reaction vessel, and react at 0-5°C for 55 minutes.
3) Drain and wash three times with DMF, methanol and DMF respectively, and drain dry.
4. Preparation of Fmoc-Leu-Leu-Leu-Lys(Boc)-resin
1) Add 1000ml of unhatting reagent, react at 21-23°C for 18 minutes, drain dry, wash with DMF, methanol and DMF three times each, and drain dry.
2) Take 53.0g Fmoc-Leu-OH, 57.0g HATU, and 20.5g HOAt, dissolve with 520ml of peptide reagent, add to the reaction vessel, and react at 0-5°C for 55 minutes.
3) Drain and wash three times with DMF, methanol and DMF respectively, and drain dry.
5. Preparation of Fmoc-Leu-Leu-Leu-Leu-Leu-Lys(Boc)-resin
1) Add 1000ml of unhatting reagent, react at 21-23°C for 18 minutes, drain dry, wash with DMF, methanol and DMF three times each, and drain dry.
2) Take 53.0g Fmoc-Leu-OH, 57.0g HATU, and 20.5g HOAt, dissolve with 520ml of peptide reagent, add to the reaction vessel, and react at 0-5°C for 55 minutes.
3) Drain and wash three times with DMF, methanol and DMF respectively, and drain dry.
6. Preparation of Fmoc-Lys(Boc)-Leu-Leu-Leu-Leu-Leu-Lys(Boc)-resin
1) Add 1000ml of unhatting reagent, react at 21-23°C for 18 minutes, drain dry, wash with DMF, methanol and DMF three times each, and drain dry.
2) Take 70.5g of Fmoc-Lys(Boc)-OH, 57.0g HATU, and 20.5g HOAt, dissolve them with 520ml of peptide reagent, add them to the reaction vessel, and react at 0-5°C for 55 minutes.
3) Drain and wash three times with DMF, methanol and DMF respectively, and drain dry.
7. Preparation of Fmoc-Leu-Lys(Boc)-Leu-Leu-Lys(Boc)-resin
1) Add 1000ml of uncapping reagent, react at 27-29°C for 15 minutes, drain and wash three times with DMF, methanol and DMF respectively, and drain dry.
2) Take 74.2g of Fmoc-Leu-OH, 79.5g HATU, and 28.6g of HOAt, dissolve them with 760ml of leptide reagent, add them to the reaction vessel, and react at 19-21°C for 45 minutes.
3) Drain and wash three times with DMF, methanol and DMF respectively, and drain dry.
8. Preparation of Fmoc-Leu-Leu-Lys(Boc)-Leu-Lys(Boc)-resin
1) Add 1000ml of unhatting reagent, react at 21-23°C for 18 minutes, drain dry, wash with DMF, methanol and DMF three times each, and drain dry.
2) Take 53.0g Fmoc-Leu-OH, 57.0g HATU, and 20.5g HOAt, dissolve with 520ml of peptide reagent, add to the reaction vessel, and react at 0-5°C for 55 minutes.
3) Drain and wash three times with DMF, methanol and DMF respectively, and drain dry.
9. Preparation of Fmoc-Leu-Leu-Leu-Lys(Boc)-Leu-Leu-Lys(Boc)-resin
1) Add 1000ml of unhatting reagent, react at 21-23°C for 18 minutes, drain dry, wash with DMF, methanol and DMF three times each, and drain dry.
2) Take 53.0g Fmoc-Leu-OH, 57.0g HATU, and 20.5g HOAt, dissolve with 520ml of peptide reagent, add to the reaction vessel, and react at 0-5°C for 55 minutes.
3) Drain and wash three times with DMF, methanol and DMF respectively, and drain dry.
10. Preparation of Fmoc-Leu-Leu-Leu-Leu-Lys(Boc)-Leu-Leu-Leu-Leu-D-Tyr (tBu)-Resin
1) Add 1000ml of unhatting reagent, react at 21-23°C for 18 minutes, drain dry, wash with DMF, methanol and DMF three times each, and drain dry.
2) Take 53.0g Fmoc-Leu-OH, 57.0g HATU, and 20.5g HOAt, dissolve with 520ml of peptide reagent, add to the reaction vessel, and react at 0-5°C for 55 minutes.
3) Drain and wash three times with DMF, methanol and DMF respectively, and drain dry.
11. Preparation of Fmoc-Lys(Boc)-Leu-Leu-Leu-Leu-Leu-Lys(Boc)-Leu-Leu-Lys(Boc)-resin
1) Add 1000ml of unhatting reagent, react at 21-23°C for 18 minutes, drain dry, wash with DMF, methanol and DMF three times each, and drain dry.
2) Take 70.5g of Fmoc-Lys(Boc)-OH, 57.0g HATU, and 20.5g HOAt, dissolve them with 520ml of peptide reagent, add them to the reaction vessel, and react at 0-5°C for 55 minutes.
3) Drain and wash three times with DMF, methanol and DMF respectively, and drain dry.
12. Preparation of Fmoc-Lue-Lys(Boc)-Leu-Leu-Leu-Leu-Lys(Boc)-Leu-Lys(Boc)-resin
1) Add 1000ml of unhatting reagent, react at 21-23°C for 18 minutes, drain dry, wash with DMF, methanol and DMF three times each, and drain dry.
2) Take 53.0g Fmoc-Leu-OH, 57.0g HATU, and 20.5g HOAt, dissolve with 520ml of peptide reagent, add to the reaction vessel, and react at 0-5°C for 55 minutes.
3) Drain and wash three times with DMF, methanol and DMF respectively, and drain dry.
13. Preparation of Fmoc-Leu-Lue-Lys (Boc)-Leu-Leu-Leu-Leu-Lys(Boc)-Leu-Leu-Lys (Boc)-Resin
1) Add 1000ml of unhatting reagent, react at 21-23°C for 18 minutes, drain dry, wash with DMF, methanol and DMF three times each, and drain dry.
2) Take 53.0g Fmoc-Leu-OH, 57.0g HATU, and 20.5g HOAt, dissolve with 520ml of peptide reagent, add to the reaction vessel, and react at 0-5°C for 55 minutes.
3) Drain and wash three times with DMF, methanol and DMF respectively, and drain dry.
14. Preparation of Fmoc-Leu-Lue-Lue-Lys (Boc)-Leu-Leu-Leu-Leu
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