【药物名称】Venorphin, JVA-901
化学结构式(Chemical Structure):
参考文献No.546031
标题:A novel acetylated analogue of dynorphin A-(1-11) amide as a kappa-opioid receptor antagonist
作者:Wan, Q.; Murray, T.F.; Aldrich, J.V.
来源:J Med Chem 1999,42(16),3011
合成路线图解说明:

The compound was prepared by solid-phase peptide synthesis on a poliethylene glycol amino resin. Coupling with N(alpha)-Fmoc-N(G)-Boc-lysine (I) using O-benzotriazol-1-yl-N,N,N',N'-tetramethyluronium hexafluorophosphate (HBTU) and N-methylmorpholine (NMM) afforded the protected lysine-linked resin (II), and subsequent Fmoc deprotection provided resin (III). This was submitted to further coupling and deprotection cycles with the N(alpha)-Fmoc-protected amino acids proline (IV), N(G)-(2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl)arginine (VI), D-alanine (VIII), N(G)-Pbf-arginine (VI), and again N(G)-Pbf-arginine (VI) yielding peptide resins (V), (VII), (IX), (X) and (XI).

合成路线图解说明:

The coupling and deprotection cycles were continued with leucine (XII), N(in)-Boc-tryptophan (XIV), and again N(in)-Boc-tryptophan (XIV) affording peptide resins (XIII), (XV) and (XVI).

合成路线图解说明:

Further coupling and deprotection cycles with N(epsilon)-Boc-lysine (I), and O-tert-butyl-tyrosine (XVIII), yielded the peptide resins (XVII) and (XIX), respectively. Then, acetylation of the free amino group of peptide resin (XIX) with Ac2O, and final deprotection and cleavage from the resin by means of moist trifluoroacetic acid, phenol and triisopropylsilane furnished the title peptide amide.

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