LGD-1550, ALRT-550, ALRT-1550, LG-1550
(2E,4E,6E)-7-[3,5-二(1,1-二甲基乙基)苯基]-3-甲基-2,4,6-辛三烯酸Chemical Name: (2E,4E,6E)-7-(3,5-Di-tert-butylphenyl)-3-methylocta-2,4,6-trienoic acid
CAS No. 178600-20-9, 178600-19-6 (stereoisomer)
项目整合开发状态: Phase II
项目研究机构: Ligand (Originator)
合成路线:Addition of methyllithium to 3,5-di-tert-butylbenzoic acid (I) at -78 C gave acetophenone (II).The Horner-Emmons condensation of acetophenone (II) with diethyl (cyanomethyl)phosphonate (III) resulted in a mixture of isomeric alpha,beta-unsaturated nitriles (IV).After isolation of the major E-isomer by preparative TLC,cyano group reduction employing DIBAL in CH2Cl2 at -78 C provided aldehyde (V).This was subjected to a new Horner-Emmons condensation with phosphonate (VI) to provide the octatrienoate ester (VII).The target carboxylic acid was then prepared by saponification of ester (VII) with methanolic KOH.
📌 参考资料/链接：
参考文献标题:Novel trienoic retinoid cpds.and methods
文献作者:Boehm,M.F.; Zhang,L.; Bennani,Y.L.; Nadzan,A.M.(Ligand Pharmaceuticals,Inc.)
参考来源:JP 1998511948; US 5721103; US 6083977; WO 9620913.
📄 详细内容
合成路线:Addition of methyllithium to 3,5-di-tert-butylbenzoic acid (I) at -78 C gave acetophenone (II).The Horner-Emmons condensation of acetophenone (II) with diethyl (cyanomethyl)phosphonate (III) resulted in a mixture of isomeric alpha,beta-unsaturated nitriles (IV).After isolation of the major E-isomer by preparative TLC,cyano group reduction employing DIBAL in CH2Cl2 at -78 C provided aldehyde (V).This was subjected to a new Horner-Emmons condensation with phosphonate (VI) to provide the octatrienoate ester (VII).The target carboxylic acid was then prepared by saponification of ester (VII) with methanolic KOH.
参考文献标题:Discovery of novel retinoic acid receptor agonists having potent antiproliferative activity in cervical cancer cells
文献作者:Zhang,L.; Nadzan,A.M.; Heyman,R.A.; Love,D.L.; Mais,D.E.; Croston,G.E.; Lamph,W.W.; Boehm,M.F.
参考来源:J Med Chem 1996,39(14),2659.
产品链接: CAS No. 178600-20-9›› 产品链接: CAS No.178600-19-6››