JE-2178
N-tert-丁基-3-[3(S)-[Nalpha-[2-[3-(二甲基氨基)苯氧基]乙酰]-L-伐雷胺]-2(S)-羟基-4-苯基丁基]-5,5-二甲基噻唑烷-4(R)-羧酰胺Chemical Name: N-tert-Butyl-3-[3(S)-[Nalpha-[2-[3-(dimethylamino)phenoxy]acetyl]-L-valylamino]-2(S)-hydroxy-4-phenylbutyryl]-5,5-dimethylthiazolidine-4(R)-carboxamide
CAS No. 210181-19-4
项目整合开发状态: Preclinical
项目研究机构: Japan Energy (Originator)
合成路线:Coupling of carboxylic acid (I) with tert-butylamine (II) by means of EDC-HOBt in CH2Cl2 affords carboxamide (III),whose Boc group is removed by treatment with HCl/dioxane to provide compound (IV).Coupling of thiazolidine (IV) to Boc-protected allophenylnorstatine (V) by means of DCC and HOBt in EtOAc provides derivative (VI),whose is deprotected by treatment with HCl/dioxane to yield (VII),which is then coupled to Boc-Val-OH (VIII) with EDC-HOBt in DMF to furnish compound (IX).On the other hand,aminophenol derivative (XI) is condensed with benzyl chloroacetate (XII) in DMF in the presence of K2CO3 to furnish derivative (XIII),which is then debenzylated by hydrogenation over Pd/C in MeOH to yield acetic acid derivative (XIV).Finally,the Boc group of (IX) is removed with HCl/dioxane and the resulting amine (X) is coupled to carboxylic acid (XIV) by first treatment with N-hydroxy-5-norbornene-2,3-dicarboximide (HONB) and DCC in CH2Cl2 followed by treatment with Et3N in DMF.Alternatively,the coupling can be performed by means of EDC and HOBt in DMF.
📌 参考资料/链接：
参考文献标题:Novel tripeptide cpds.and anti-AIDS drugs
文献作者:Terashima,K.; Mimoto,T.; Takaku,H.; Nojima,S.; Kiso,Y.(Japan Energy Corp.)
参考来源:EP 0900566; WO 9829118
📄 详细内容
合成路线:Coupling of carboxylic acid (I) with tert-butylamine (II) by means of EDC-HOBt in CH2Cl2 affords carboxamide (III),whose Boc group is removed by treatment with HCl/dioxane to provide compound (IV).Coupling of thiazolidine (IV) to Boc-protected allophenylnorstatine (V) by means of DCC and HOBt in EtOAc provides derivative (VI),whose is deprotected by treatment with HCl/dioxane to yield (VII),which is then coupled to Boc-Val-OH (VIII) with EDC-HOBt in DMF to furnish compound (IX).On the other hand,aminophenol derivative (XI) is condensed with benzyl chloroacetate (XII) in DMF in the presence of K2CO3 to furnish derivative (XIII),which is then debenzylated by hydrogenation over Pd/C in MeOH to yield acetic acid derivative (XIV).Finally,the Boc group of (IX) is removed with HCl/dioxane and the resulting amine (X) is coupled to carboxylic acid (XIV) by first treatment with N-hydroxy-5-norbornene-2,3-dicarboximide (HONB) and DCC in CH2Cl2 followed by treatment with Et3N in DMF.Alternatively,the coupling can be performed by means of EDC and HOBt in DMF.
参考文献标题:Structure-activity relationship of orally potent tripeptide-based HIV protease inhibitors containing hydroxymethylcarbonyl isostere
文献作者:Mimoto,T.; Hattori,N.; Takaku,H.; Kisanuki,S.; Fukazawa,T.; Terashima,K.; Kato,R.; Nojima,S.; Misawa,S.; Ueno,T.; Imai,J.; Enomoto,H.; Tanaka,S.; Sakikawa,H.; Shintani,M.; Hayashi,H.; Kiso,Y.
参考来源:Chem Pharm Bull 2000,48(9),1310
产品链接: CAS No. 210181-19-4››