LK-423
Chemical Name: 2-[2-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)ethoxy]acetyl-L-alanyl-D-glutamic acid 1-amide; 2-(2-Phathalimidoethoxy)acetyl-L-alanyl-D-isoglutamine
CAS No. 142489-46-1
项目整合开发状态: Preclinical
项目研究机构: LEK (Originator), University of Ljubljana (Originator), Fujimoto (Licensee)
合成路线:The reaction of phthalimidocarboxylic acid ethyl ester (I) with 2-(2-aminoethoxy)ethanol (II) in THF gives N-[2-(2-hydroxyethoxy)ethyl]phthalimide (III),which is oxidized with CrO3/sulfuric acid in acetone yielding 2-(phthalimidoethoxy)acetic acid (IV).The condensation of (IV) with L-alanyl-D-isoglutamine benzyl ester (V) by means of phenylphosphoryl azide (DPPA) and triethylamine in DMF gives N-[2-(2-phthalimidoethoxy)acetyl]-L-alanyl-D-isoglutamine benzyl ester (VI),which is finally debenzylated by hydrogenation over Pd/C in acetic acid.
📌 参考资料/链接：
参考文献标题:Novel N-acyldipeptides,processes for the preparation thereof and pharmaceutical compsns.containing the same
文献作者:Pecar,S.; Sollner,M.; Urleb,U.; Kikelj,D.; Marc,G.; Krbavcic,A.; Kotnik,V.; Wraber-Herzog,B.; Simcic,S.; Ihan,A.; Klamfer,L.; Provsic,L.; Kopitar,Z.; Stalc,A.(LEK Pharmaceutical and Chemical Co.; University of Ljubljana)
参考来源:EP 0477912; JP 1994220087
📄 详细内容
合成路线:The reaction of phthalimidocarboxylic acid ethyl ester (I) with 2-(2-aminoethoxy)ethanol (II) in THF gives N-[2-(2-hydroxyethoxy)ethyl]phthalimide (III),which is oxidized with CrO3/sulfuric acid in acetone yielding 2-(phthalimidoethoxy)acetic acid (IV).The condensation of (IV) with L-alanyl-D-isoglutamine benzyl ester (V) by means of phenylphosphoryl azide (DPPA) and triethylamine in DMF gives N-[2-(2-phthalimidoethoxy)acetyl]-L-alanyl-D-isoglutamine benzyl ester (VI),which is finally debenzylated by hydrogenation over Pd/C in acetic acid.
参考文献标题:Synthesis of phthalimido-desmuramylpeptide analogues as potential immunomodulating agents
文献作者:Urleb,U.; et al.
参考来源:Arch Pharm 1995,328(2),113