GPI-1511
Chemical Name: 1-(3,3-Dimethyl-2-oxopentanoyl)piperidine-2(S)-carbothioic acid S-(3,3-diphenylpropyl) ester
CAS No. 252770-39-1, 205388-57-4 (undefined stereoch.)
项目整合开发状态: Preclinical
项目研究机构: Guilford Pharmaceuticals (Originator)
合成路线:Acylation of methyl pipecolinate (I) with methyl oxalyl chloride (II) provides oxamate (III).Subsequent addition of 1,1-dimethylpropylmagnesium chloride (IV) to oxamate (III) gives rise to keto amide (V).The methyl ester group of (V) is then hydrolyzed by means of LiOH,yielding the intermediate carboxylic acid (VI)
合成路线:3,3-Diphenyl-1-propanol (VII) is converted into the corresponding alkyl bromide (VIII) by treatment with CBr4 and PPh3.Reaction of bromide (VIII) with thiourea provides the isothiouronium salt (IX),which is further hydrolyzed to thiol (X) under alkaline conditions.Finally,acylation of thiol (X) with carboxylic acid (VI) by means of DCC yields the target thioester
📌 参考资料/链接：
参考文献标题:Synthesis of N-glyoxyl prolyl and pipecolyl amides and thioesters and evaluation of their in vitro and in vivo nerve regenerative effects
文献作者:Hamilton,G.S.; Wu,Y.-Q.; Limburg,D.C.; Wilkinson,D.E.; Vaal ,M.J.; Li,J.-H.; Thomas,C.; Huang,W.; Sauer,H.; Ross,D.T.; Soni,R.; Chen,Y.; Guo,H.; Howorth,P.; Valentine,H.; Liang,S.; Spicer,D.; Fuller,M.; Steiner,J.P
参考来源:J Med Chem 2002,45(16),3549