120-1032
Chemical Name: 2-[1-(2-Amino-2-oxoethyl)-3-benzyl-2-ethylindolizin-8-yloxy]acetic acid
CAS No. 177556-87-5
项目整合开发状态: Biological Testing
项目研究机构: Shionogi (Originator)
合成路线:The hydrogenation of pyridineacrylate (I) produced a mixture of the benzyl-protected pyridinepropionate (II) and the debenzylated analogue (III),which were separated by column chromatography.Ester (III) was converted into amide (IV) upon treatment with aqueous ammonia,and further protected with benzyl chloride to afford (V).Cyclization with 1-bromo-2-butanone (VI) in the presence of NaHCO3 furnished indolizidine (VII).This was acylated with benzoyl chloride in boiling benzene to give ketone (VIII),which was reduced to the benzyl derivative (IX) by means of borane-tert-butyl amine complex and AlCl3.Hydrogenolytic deprotection of the benzyl ether of (IX) afforded phenol (X),which was alkylated with methyl bromoacetate and NaH to yield the corresponding esther (XI).Finally,hydrolysis of the methyl ester (XI) with LiOH provided the target carboxylic acid.
📌 参考资料/链接：
参考文献标题:Indolizine sPLA2 inhibitors
文献作者:Dillard,R.D.; Hagishita,S.; Ohtani,M.(Eli Lilly and Company; Shionogi & Co.Ltd.)
参考来源:EP 0772596; JP 1998505584; WO 9603383
📄 详细内容
合成路线:The hydrogenation of pyridineacrylate (I) produced a mixture of the benzyl-protected pyridinepropionate (II) and the debenzylated analogue (III),which were separated by column chromatography.Ester (III) was converted into amide (IV) upon treatment with aqueous ammonia,and further protected with benzyl chloride to afford (V).Cyclization with 1-bromo-2-butanone (VI) in the presence of NaHCO3 furnished indolizidine (VII).This was acylated with benzoyl chloride in boiling benzene to give ketone (VIII),which was reduced to the benzyl derivative (IX) by means of borane-tert-butyl amine complex and AlCl3.Hydrogenolytic deprotection of the benzyl ether of (IX) afforded phenol (X),which was alkylated with methyl bromoacetate and NaH to yield the corresponding esther (XI).Finally,hydrolysis of the methyl ester (XI) with LiOH provided the target carboxylic acid.
参考文献标题:Potent inhibitors of secretory phospholipase A2: Synthesis and inhibitory activities on indolizine and indene derivatives
文献作者:Hagishita,S.; Yamda,M.; Shirahase,K.; Okada,T.; Murakami,Y.; Ito,Y.; Matsuura,T.; Wada,M.; Kato,T.; Ueno,M.; Chikazawa,Y.; Yamada,K.; Ono,T.; Teshirogi,I.; Ohtani,M.
参考来源:J Med Chem 1996,39(19),3636