新产品编号:921233
Chemical Name: 4(R)-(1-Benzothien-2-ylmethyl)-D-glutamic acid
CAS No. 400625-61-8
项目整合开发状态: Preclinical
项目研究机构: Lilly (Originator)
合成路线:D-Glutamic acid (I) is treated with SOCl2 in EtOH to produce ethyl D-pyroglutamate (II).Further protection of (II) with di-tert-butyl dicarbonate yields the N-Boc pyroglutamate (III) (1).The lithiated derivative of (III) is alkylated with 2-(bromomethyl)benzothiophene (IV) to afford the trans alkylated isomer (V).Basic hydrolysis of (V) produces the N-Boc amino diacid (VI).Then,acidic Boc group cleavage in (VI),followed by treatment of the resultant hydrochloride salt with propylene oxide in MeOH leads to the free aminoacid (1,2).
📌 参考资料/链接：
参考文献标题:Chemical cpds.
文献作者:Martin,J.A.; Ezquerra-Carrera,J.; Tebbe,M.J.; De Dios,A.; Prieto,L.; McGee,J.E.; Rubio-Esteban,A.; Smith,M.C.(Eli Lilly and Company)
参考来源:WO 0214261
📄 详细内容
合成路线:D-Glutamic acid (I) is treated with SOCl2 in EtOH to produce ethyl D-pyroglutamate (II).Further protection of (II) with di-tert-butyl dicarbonate yields the N-Boc pyroglutamate (III) (1).The lithiated derivative of (III) is alkylated with 2-(bromomethyl)benzothiophene (IV) to afford the trans alkylated isomer (V).Basic hydrolysis of (V) produces the N-Boc amino diacid (VI).Then,acidic Boc group cleavage in (VI),followed by treatment of the resultant hydrochloride salt with propylene oxide in MeOH leads to the free aminoacid (1,2).
参考文献标题:4-Substituted D-glutamic acid analogues: The first potent inhibitors of glutamate racemase (MurI) enzyme with antibacterial activity
文献作者:De Dios,A.; Prieto,L.; Martin,J.A.; Rubio,A.; Ezquerra,J.; Tebbe,M.; L髉ez de Uralde,B.; Mart韓,J.; S醤chez,A.; LeTourneu,D.L.; McGee,J.E.; Boylan,C.; Parr,T.R.; Smith,M.C.
参考来源:J Med Chem 2002,45(20),4559