LY-339687
Chemical Name: 4-(1-Ethylpropylidene)-L-glutamic acid
项目整合开发状态: Biological Testing
项目研究机构: Lilly (Originator), NPS Allelix (Originator)
合成路线:Treatment of ethyl N-Boc-(S)-pyroglutamate (I) with lithium hexamethyldisilazide in THF at -78 C,followed by aldol condensation of the resulting lithium enolate with cyclopentanone (II) in the presence of boron trifluoride etherate,furnished adduct (III).Dehydration of the alcohol group of (III) to produce olefin (IV) was achieved by treatment of (III) with methanesulfonyl chloride and triethylamine.Hydrolysis of the ester and lactam groups of (IV) by means of LiOH afforded diacid (V).The N-Boc group of (V) was finally cleaved with HCl in EtOH.
合成路线:Treatment of ethyl N-Boc-(S)-pyroglutamate (I) with lithium hexamethyldisilazide in THF at -78 C,followed by aldol condensation of the resulting lithium enolate with 3-pentanone (II) in the presence of boron trifluoride etherate,furnished adduct (III).Dehydration of the alcohol group of (III) to produce olefin (IV) was achieved by treatment of (III) with methanesulfonyl chloride and triethylamine.Hydrolysis of the ester and lactam groups of (IV) by means of LiOH afforded diacid (V).The N-Boc group of (V) was finally cleaved with HCl in EtOH.
📌 参考资料/链接：
参考文献标题:Glutamic acid derivs.and pharmaceutical compsns.for the treatment of central nervous system disorders
文献作者:Rubio Esteban,A.; Pedregal Tercero,C.(Lilly SA)
参考来源:EP 0867430; ES 2133095; JP 1998279542
📄 详细内容
合成路线:Treatment of ethyl N-Boc-(S)-pyroglutamate (I) with lithium hexamethyldisilazide in THF at -78 C,followed by aldol condensation of the resulting lithium enolate with cyclopentanone (II) in the presence of boron trifluoride etherate,furnished adduct (III).Dehydration of the alcohol group of (III) to produce olefin (IV) was achieved by treatment of (III) with methanesulfonyl chloride and triethylamine.Hydrolysis of the ester and lactam groups of (IV) by means of LiOH afforded diacid (V).The N-Boc group of (V) was finally cleaved with HCl in EtOH.
合成路线:Treatment of ethyl N-Boc-(S)-pyroglutamate (I) with lithium hexamethyldisilazide in THF at -78 C,followed by aldol condensation of the resulting lithium enolate with 3-pentanone (II) in the presence of boron trifluoride etherate,furnished adduct (III).Dehydration of the alcohol group of (III) to produce olefin (IV) was achieved by treatment of (III) with methanesulfonyl chloride and triethylamine.Hydrolysis of the ester and lactam groups of (IV) by means of LiOH afforded diacid (V).The N-Boc group of (V) was finally cleaved with HCl in EtOH.
参考文献标题:4-Alkylidenyl glutamic acids,potent and selective GluR5 agonists
文献作者:Baker,S.R.; Bleakman,D.; Ezquerra,J.; Ballyk,B.A.; Deverill,M.; Ho,K.; Kamboj,R.K.; Collado,I.; Dominguez,C.; Escribano,A.; Mateo,A.I.; Pedregal,C.; Rubio,A.
参考来源:Bioorg Med Chem Lett 2000,10(16),1807