PD-151307
Chemical Name: Perhydroazepin-1-ylcarbonyl-L-leucyl-4-O-(benzyl)-L-tyrosine tert-butyl ester
项目整合开发状态: Biological Testing
项目研究机构: Neurex (Originator), Pfizer (Originator)
合成路线:By condensation of N-(perhydroazepin-1-ylcarbonyl)-L-leucine (V) with 4-O-benzyl-L-tyrosine tert-butyl ester (VIII) by means of HOBT and diisopropylethylamine in DMF.The two peptide intermediates (V) and (VIII) have been obtaines a follows:L-Leucine fragment (V): The carbonatation of perhydroazepine (I) with CO2 and pyridine followed by reaction with SOCl2 gives perhydroazepin-1-ylcarbonyl chloride (II),which is condensed with L-leucine benzyl ester (III) yielding the N-acylated leucine ester (IV).Finally,this compound is debenzylated by hydrogenation with H2 over Pd/C in THF to afford the target intermediate (V).Tyrosine fragment (VIII): By esterification of 4-O-benzyl-L-tyrosine (VI) with isobutylene (VII) by means of sulfuric acid in dioxane.
📌 参考资料/链接：
参考文献标题:Peptidyl calcium channel blockers
文献作者:Roth,B.D.; Connor,D.T.; Malone,T.C.; Hamilton,H.W.; Rafferty,M.F.; Hu,L.-Y.; Cody,W.L.; He,J.X.; Nadasdi,L.; Brogley,L.; Urge,L.; Silva,D.F.; Song,Y.; Szoke,B.G.; Booth,R.J.; Lescosky,J.(Neurex Corp.; Pfizer Inc.)
参考来源:US 6423689
📄 详细内容
合成路线:By condensation of N-(perhydroazepin-1-ylcarbonyl)-L-leucine (V) with 4-O-benzyl-L-tyrosine tert-butyl ester (VIII) by means of HOBT and diisopropylethylamine in DMF.The two peptide intermediates (V) and (VIII) have been obtaines a follows:L-Leucine fragment (V): The carbonatation of perhydroazepine (I) with CO2 and pyridine followed by reaction with SOCl2 gives perhydroazepin-1-ylcarbonyl chloride (II),which is condensed with L-leucine benzyl ester (III) yielding the N-acylated leucine ester (IV).Finally,this compound is debenzylated by hydrogenation with H2 over Pd/C in THF to afford the target intermediate (V).Tyrosine fragment (VIII): By esterification of 4-O-benzyl-L-tyrosine (VI) with isobutylene (VII) by means of sulfuric acid in dioxane.
参考文献标题:Identification and SAR studies of PD 151307,a novel N-type calcium channel blocker
文献作者:Malone,T.; et al.
参考来源:217th ACS Natl Meet (March 21 1999,Anaheim) 1999,Abst MEDI 122