PRL-2915

L-阿拉尼胺,4-氯-L-苯丙酰-D-半氨基-3-(3-吡啶基)-L-异丙酰-D-色氨酸-L-赖氨酸-3-甲基-甲基-L-戊醇-L-半氨酸-3-(2-萘基)-,环状(2-7)-二硫化物Chemical Name: 4-Chloro-L-phenylalanyl-D-cysteinyl-3-(3-pyridyl)-L-alanyl-D-tryptophyl-L-lysyl-3-(methyl)-L-valyl-L-cysteinyl-3-(2-naphthyl)-L-alaninamide cyclic (2-7) disulfide
CAS No. 209006-18-8
项目整合开发状态: Biological Testing
项目研究机构: Biomeasure (Originator), Tulane University (Originator)
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.