新产品编号:965529
Chemical Name: 1-O-[2-[N-[4-[(5R,5aR,8aR,9S)-9-[4,6-O-[(1R)-Ethylidene]-beta-D-glucopyranosyloxy]-6-oxo-5,5a,6,8,8a,9-hexahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-5-yl]-2,6-dimethoxyphenoxycarbonyl]-N-methylamino]-4-nitrophenyl]-beta-D-glucuronic acid; 1-O-[2-[N-(Etoposide-4'-O-ylcarbonyl)-N-methylamino]-4-nitrophenyl]-beta-D-glucuronic acid
CAS No. 515824-41-6
项目整合开发状态: Biological Testing
项目研究机构: CNRS (Originator), Institut Curie (Originator)
合成路线:The protected glucuronic acid derivative (I) is hydrolyzed under alkaline conditions to furnish (II).The alcoholic hydroxyl groups of (II) are subsequently protected as the silyl ether (III) employing t-butyldimethylsilyl triflate in the presence of DMAP.The carboxyl group of (III) is further converted to the corresponding benzyl ester (IV) by DCC-mediated coupling with benzyl alcohol.Acylation of amine (IV) with phosgene leads to the carbamyl chloride (V).(1,2)
合成路线:Reaction of etoposide (VI) with acid chloride (V) produces the carbamate adduct (VII).The silyl protecting groups of (VII) are then removed by treatment with HF-pyridine yielding triol (VIII).Finally,the benzyl ester function of (VIII) is deprotected by transfer hydrogenolysis in the presence of cyclohexadiene and Pd/C.(1,2)
📌 参考资料/链接：
参考文献标题:Derivs.of etoposide and analogs,and pharmaceutical compsns.containing them
文献作者:Monneret,C.; Schmidt,F.(CNRS (Centre National de la Recherche Scientifique); Institut Curie)
参考来源:WO 0335661
📄 详细内容
合成路线:The protected glucuronic acid derivative (I) is hydrolyzed under alkaline conditions to furnish (II).The alcoholic hydroxyl groups of (II) are subsequently protected as the silyl ether (III) employing t-butyldimethylsilyl triflate in the presence of DMAP.The carboxyl group of (III) is further converted to the corresponding benzyl ester (IV) by DCC-mediated coupling with benzyl alcohol.Acylation of amine (IV) with phosgene leads to the carbamyl chloride (V).(1,2)
合成路线:Reaction of etoposide (VI) with acid chloride (V) produces the carbamate adduct (VII).The silyl protecting groups of (VII) are then removed by treatment with HF-pyridine yielding triol (VIII).Finally,the benzyl ester function of (VIII) is deprotected by transfer hydrogenolysis in the presence of cyclohexadiene and Pd/C.(1,2)
参考文献标题:Prodrug mono therapy: Synthesis and biological evaluation of an etoposide glucuronide-prodrug
文献作者:Schmidt,F.; Monneret,C.
参考来源:Bioorg Med Chem 2003,11(10),2277