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项目整合精选>>>Pobilukast, SK&F-104353-Q(as edamide, monohydrate), SK&F-104353-Z2(diNa salt), SK&F-104353
Pobilukast, SK&F-104353-Q(as edamide, monohydrate), SK&F-104353-Z2(diNa salt), SK&F-104353
(2S,3R)-3-(2-羧基乙基硫基)-2-羟基-3-[2-(8-苯基辛基)苯基]丙酸Chemical Name: 2(S)-Hydroxy-3(R)-(2-carboxyethylthio)-3-[2-(8-phenyloctyl)phenyl]propanoic acid
CAS No. 107023-41-6, 137232-03-2 (ethylenediamine (1:1), monohydrate)
项目整合开发状态: Phase III
项目研究机构: GlaxoSmithKline (Originator)
合成路线:The synthesis of SK&F 104353 (Ia) was carried out as follows:Darzens condensation of 2-(8-phenyloctyl)benzaldehyde (II) with methyl chloroacetate afforded the trans-epoxide (III),which was opened with methyl mercaptopropionate to give a mixture of regioisomers (IV) and (V).Reaction of this mixture of regioisomers with sodium methoxide produced a mixture of (IV) and starting material (II),which was readily separated by chromatography.Sodium hydroxide saponification of diester (IV) afforded the racemic diacid (I),which was resolved as the alpha-methyl-4-bromobenzylamine salt to give,after conversion to the respective free acids,the enantiomers (Ia) and (Ib).
📌 参考资料/链接：
参考文献标题:High affinity leukotriene receptor antagonists.Synthesis and pharmacological characterization of 2-hydroxy-3-(2-carboxy-ethylthio)-3-[2-(8-phenoyloctyl)propanoic acids
文献作者:Gleason,J.G.; Hall,R.F.; Perchonock,C.D.; et al.
参考来源:J Med Chem 1987,30(6),959-61
📄 详细内容
合成路线:The synthesis of SK&F 104353 (Ia) was carried out as follows:Darzens condensation of 2-(8-phenyloctyl)benzaldehyde (II) with methyl chloroacetate afforded the trans-epoxide (III),which was opened with methyl mercaptopropionate to give a mixture of regioisomers (IV) and (V).Reaction of this mixture of regioisomers with sodium methoxide produced a mixture of (IV) and starting material (II),which was readily separated by chromatography.Sodium hydroxide saponification of diester (IV) afforded the racemic diacid (I),which was resolved as the alpha-methyl-4-bromobenzylamine salt to give,after conversion to the respective free acids,the enantiomers (Ia) and (Ib).
参考文献标题:SK&F-104353
文献作者:Hay,D.W.P.; Newton,J.F.; Torphy,T.J.; Gleason,J.G.
参考来源:Drugs Fut 1990,15(3),240
合成路线:A new enantioselective synthesis of SK&F-104353 has been reported:The compound can be prepared in two related ways:1) The condensation of 2-(8-phenyloctyl)benzaldehyde (I) with 2'-acetonaphthone (II) by means of NaOEt in ethanol gives (E)-1-(2-naphthyl)-3-[2-(8-phenyloctyl)phenyl]-2-propen-1-one (III),which is regioselectively epoxidized with H2O2 and poly-L-leucine in hexane/water to yield the corresponding (2R-trans)-epoxide (IV).The oxidation of (IV) with m-chloroperbenzoic acid in CH2Cl2 affords (2R-trans)-3-[2-(8-phenyloctyl)phenyl]oxirane-2-carboxylic acid 2-naphthyl ester (V),which is hydrolyzed with LiOH in ethanol to the corresponding lithium salt (VI).Finally,(VI) is condensed with 3-mercaptopropionic acid methyl ester (VII) by means of NaOMe in methanol to give a mixture of regioisomers that are separated by column chromatography.2) The reaction of the oxiranyl ester (V) with ammonia in acetone/water yields the corresponding amide (VIII),which is condensed with the sodium salt of propenoate (VII) by means of titanium tetrapropoxide in CH2Cl2 to afford the amide ester (X).The basic hydrolysis of (X) with NaOH in methanol gives the corresponding acid amide (XI),which is finally submitted to acid hydrolysis with aqueous HCl.
参考文献标题:A practical,enantioselective synthesis of SK&F 104353
文献作者:Flisak,J.R.; Lantos,I.; Snyder,L.; Gombatz,K.J.; Mendelson,W.L.; Jarmas,A.A.; Holmes,M.M.; Remich,J.J.; Novack,V.J.
参考来源:J Org Chem 1993,58(23),6247
产品链接: CAS No. 107023-41-6›› 产品链接: CAS No.137232-03-2››