반응 #1922747

ord-47b327b03b7c4ad1b14d27e6bfa0619d

반응 방정식

O=C(N[C@H](Cc1ccc(Cl)cc1)C(=O)O)OCC1c2ccccc2-c2ccccc21
Fmoc-(D)Phe(4-Cl)-OH
CCN(C(C)C)C(C)C
diisopropylethylamine
CN(C(=O)OCC1c2ccccc2-c2ccccc21)[C@H](Cc1ccccc1)C(=O)O
Fmoc-NMe(D)Phe-OH
N[C@H](Cc1ccc(Cl)cc1)C(=O)O
H-(D)Phe(4-Cl)
Clc1ccccc1C(Cl)(c1ccccc1)c1ccccc1
2-chlorotritylchloride resin
CN(C)C(On1nnc2ccccc21)=[N+](C)C.F[P-](F)(F)(F)(F)F.On1nnc2ccccc21
HBTU HOBt
CN[C@H](Cc1ccccc1)C(=O)N[C@H](Cc1ccc(Cl)cc1)C(=O)O
H-NMe(D)Phe-(D)Phe(4-Cl)

용매

반응 조건

상세 조건
See reaction.notes.procedure_details.

후처리

  1. 1
    여과the resin was filtered
  2. 2
    세척washed with DMF
  3. 3
    세척After deprotection with 20% piperidine in DMF (two treatments with 15 ml), the resin was thoroughly washed with DMF (5×10 ml)
  4. 4
    세척After extensive washing with DMF

실험 절차

Fmoc-(D)Phe(4-Cl)-OH (844 mg, 2 mmol) was coupled to 2-chlorotritylchloride resin (Alexis, 0.75 g, 1 mmol) in the presence of diisopropylethylamine (2 mmol 0.35 ml) in DMF (8 ml) by an automated procedure on an Applied Biosystems 430A peptide synthesiser. After 1 hour at ambient temperature, the resin was filtered and washed with DMF. After deprotection with 20% piperidine in DMF (two treatments with 15 ml), the resin was thoroughly washed with DMF (5×10 ml). Fmoc-NMe(D)Phe-OH (803 mg, 2 mmol) was coupled to the resin-bound H-(D)Phe(4-Cl) by the standard HBTU/HOBt chemistry similar to that used in example 3. After extensive washing with DMF, the deprotection procedure described above was repeated to give H-NMe(D)Phe-(D)Phe(4-Cl)-resin. Fmoc-(D)Lys(BOC)-OH (938 mg, 2 mmol) was coupled by the HATU procedure (see J Chem Soc. Chem Comm. 1994, 201). After 1 hour at ambient temperature the resin as filtered and washed with DMF. After deprotection and extensive washing with DMF, cyclohexane carboxylic acid (256 mg, 2 mmol) was coupled by standard HBTU/HOBt chemistry similar to that described above to the resin bound tripeptide to give cyclohexyl-(D)Lys(BOC)-NMe(D)Phe-(D)Phe(4-Cl) on the resin. The peptide resin was collected and washed with methanol and dried, in vacuo, at 50° C. Yield 1.337 g (gain 587 mg).

출처

DOI: 10.6084/m9.figshare.5104873.v1특허: US06770627B1uspto-grants-2004_08