SC-alphaalphadelta9
Chemical Name: N-Benzyl-N-[2-(2,5-diphenyloxazol-4-ylcarboxamido)ethyl]-2-(decanamido)glutaramic acid
项目整合开发状态: Preclinical
项目研究机构: University of Pittsburgh (Originator)
合成路线:Protection of L-glutamic acid (I) with allyl alcohol and chlorotrimethylsilane produced the gamma-allyl ester (II).Subsequent treatment of (II) with fluorenylmethoxycarbonyl chloride afforded the N-Fmoc derivative (III).This was coupled to Wang resin using EDC and DMAP to provide the glutamate-coupled resin (IV).Removal of the Fmoc protecting group by means of piperidine gave (V),which was then condensed with decanoyl chloride (VI) yielding amide (VII).The allyl ester was then cleaved by treatment with Pd(PPh3)4 and the resulting carboxylic acid (VIII) was coupled with monoprotected diamine (IX) to furnish diamide (X).Deprotection of the allyl carbamate of (X) provided amine (XI).
合成路线:Amine (XI) was coupled to isoxazolecarboxylic acid (XII) to give (XIII).which was finally liberated from the resin by cleavage with trifluoroacetic acid in CH2Cl2.
📌 参考资料/链接：
参考文献标题:Phosphatase inhibitors and methods of use thereof
文献作者:Lazo,J.S.; Rice,R.L.; Cunningham,A.; Wipf,P.(University of Pittsburgh)
参考来源:EP 0959884; US 5700821; WO 9804257
📄 详细内容
合成路线:Protection of L-glutamic acid (I) with allyl alcohol and chlorotrimethylsilane produced the gamma-allyl ester (II).Subsequent treatment of (II) with fluorenylmethoxycarbonyl chloride afforded the N-Fmoc derivative (III).This was coupled to Wang resin using EDC and DMAP to provide the glutamate-coupled resin (IV).Removal of the Fmoc protecting group by means of piperidine gave (V),which was then condensed with decanoyl chloride (VI) yielding amide (VII).The allyl ester was then cleaved by treatment with Pd(PPh3)4 and the resulting carboxylic acid (VIII) was coupled with monoprotected diamine (IX) to furnish diamide (X).Deprotection of the allyl carbamate of (X) provided amine (XI).
合成路线:Amine (XI) was coupled to isoxazolecarboxylic acid (XII) to give (XIII).which was finally liberated from the resin by cleavage with trifluoroacetic acid in CH2Cl2.
参考文献标题:Combinatorial synthesis and biological evaluation of library of small-molecule Ser/Thr-protein phosphatase inhibitors
文献作者:Wipf,P.; Cunningham,A.; Rice,R.L.; Lazo,J.S.
参考来源:Bioorg Med Chem 1997,5(1),165