DC-41-33, PRL-2903

合成路线:The compound was prepared by solid-phase peptide synthesis on a 4-methylbenzhydrylamine-functionalized resin.Coupling of N-Boc-L-(2-naphthyl)alanine (I) with the amino resin (II) was effected by means of diisopropylcarbodiimide (DIC) to yield the protected amino acid-linked resin (III).Deprotection of the Boc group with trifluoroacetic acid provided resin (IV).This was subsequently submitted to further coupling and deprotection cycles with the protected amino acids N-Boc-S-(4-methylbenzyloxycarbonyl)-L-cysteine (V),N-Boc-L-tert-leucine (VII) and N(alpha)-Boc-N(omega)-(2-chlorobenzyloxycarbonyl)-L-lysine (IX) to afford the peptide-resins (VI),(VIII) and (X),respectively.

合成路线:Compound (X) was subsequently submitted to further coupling and deprotection cycles with the protected amino acids N-Boc-D-tryptophan (XI) and N-Boc-L-(3-pyridyl)alanine (XIII) to afford the peptide-resins (XII) and (XIV),respectively.

合成路线:Compound (XIV) was subsequently submitted to further coupling and deprotection cycles with the protected amino acids N-Boc-S-(4-methylbenzyloxycarbonyl)-D-cysteine (XV) and N-Boc-L-(4-chlorophenyl)- alanine (XVII) to afford the peptide-resins (XVI) and (XVIII),respectively.

合成路线:Cleavage of the peptide (XVIII) from the resin support with simultaneous side-chain deprotection using anhydrous HF containing the scavengers anisole and dithiothreitol produced the peptide amide (XIX).This was finally cyclized to the title disulfide employing iodine in AcOH.

合成路线:The compound was prepared by solid-phase peptide synthesis on a 4-methylbenzhydrylamine-functionalized resin using an automatic peptide synthesizer.Binding of N-Boc-3-(2-naphthyl)-L-alanine (I) to the resin was effected by double coupling,first with the 1,3-diisopropylcarbodiimide active ester,and then a second coupling with the TBTU ester to produce the amino acid-linked resin (II).Deblocking of the Boc group of (II) by treatment with trifluoroacetic acid provided resin (III).The following amino acids were then coupled and deprotected successively to (III) by the same procedure: N-Boc-S-(4-methylbenzyloxycarbonyl)-L-cysteine (IV),N-Boc-L-tert-leucine (VI),N(alpha)-Boc-N(epsilon)-(2-chlorobenzyloxycarbonyl)-L-lysine (VIII) and N-Boc-D-tryptophan (X) yielding the peptide resins (V),(VII),(IX) and (XI),respectively.

合成路线:The coupling and deprotection cycles was continued with N-Boc-L-(3-pyridyl)alanine (XII),N-Boc-S-(4-methylbenzyloxy-carbonyl)-D-cysteine (IV),and N-Boc-L-4-fluorophenylalanine (XV),yielding the peptide resins (XIII),(XIV) and (XVI),respectively.

合成路线:Cleavage of the resin support of (XVI) with simultaneous side-chain deprotection using anhydrous HF in the presence of the scavengers anisole and dithiothreitol gave the peptide amide (XVII).This was finally cyclized to the title disulfide by oxidation with iodine in AcOH.

参考文献标题:Highly potent cyclic disulfide antagonists of somatostatin
文献作者:Hocart,S.J.; Jain,R.; Murphy,W.A.; Taylor,J.E.; Coy,D.H.
参考来源:J Med Chem 1999,42(11),1863


合成路线:The compound was prepared by solid-phase peptide synthesis on a 4-methylbenzhydrylamine-functionalized resin using an automatic peptide synthesizer.Binding of N-Boc-3-(2-naphthyl)-L-alanine (I) to the resin was effected by double coupling,first with the 1,3-diisopropylcarbodiimide active ester,and then a second coupling with the TBTU ester to produce the amino acid-linked resin (II).Deblocking of the Boc group of (II) by treatment with trifluoroacetic acid provided resin (III).The following amino acids were then coupled and deprotected successively to (III) by the same procedure: N-Boc-S-(4-methylbenzyloxycarbonyl)-L-cysteine (IV),N-Boc-L-tert-leucine (VI),N(alpha)-Boc-N(epsilon)-(2-chlorobenzyloxycarbonyl)-L-lysine (VIII) and N-Boc-D-tryptophan (X) yielding the peptide resins (V),(VII),(IX) and (XI),respectively.

合成路线:The coupling and deprotection cycles was continued with N-Boc-L-(3-pyridyl)alanine (XII),N-Boc-S-(4-methylbenzyloxy-carbonyl)-D-cysteine (IV),and N-Boc-L-4-fluorophenylalanine (XV),yielding the peptide resins (XIII),(XIV) and (XVI),respectively.

合成路线:Cleavage of the resin support of (XVI) with simultaneous side-chain deprotection using anhydrous HF in the presence of the scavengers anisole and dithiothreitol gave the peptide amide (XVII).This was finally cyclized to the title disulfide by oxidation with iodine in AcOH.
参考文献标题:Examination of somatostatin involvement in the inhibitory action of GIP,GLP-1,amylin and adrenomedullin on gastric acid release using a new SRIF antagonist analogue
文献作者:Rossowski,W.J.; Cheng,B.-L.; Jiang,N.-Y.; Coy,D.-H.
参考来源:Br J Pharmacol 1998,1251081