L-644122

合成路线:The condensation of ethyl 4-methylbenzoate (I) with 2-(2-bromoethyl)-1,3-dioxolane (II) by means of lithium diisopropylamide gives ethyl 4-[3-(1,3-dioxolan-2-yl)propyl]benzoate (III),which is hydrolyzed to ethyl 4-(3-formylpropyl)benzoate (IV).The condensation of (IV) with 1-(2-aminoethyl) cyclohexanol (V) affords the corresponding imine (VI),which is cyclized with methyl thioglycolate (VII) yielding ethyl 4-[3-[3-[2-[1-hydroxycyclohexyl)ethyl]-4-oxo-2-thiazolidinyl]propyl]benzoate (VIII) .The hydrolysis of (VIII) with KOH gives L-644122 as a racemic mixture (IX),which is methylated with MeI and K2CO3 to the corresponding methyl ester (X).Esterification of (X) with (-)-camphanic acid (XI) by means of dicyclohexylcarbodumide in methylene chloride affords the diastereomeric mixture of esters (XII),which is separated into its components by fractionated crystallization in ethyl acetate hexane.Finally,the (+)-diastereomer (XIII) is hydrolyzed with KOH in refluxing toluene containing diclohexyl-18-crown-6.

参考文献标题:Intermediates for the resolution of some interphenylene-9-thia-11-oxo-12-azaprostanoic
文献作者:Bock,M.G.; di Pardo,R.M.(Merck & Co.,Inc.)
参考来源:AT 235482; AT 378189B; GB 2100733; US 4390703


合成路线:The condensation of ethyl 4-methylbenzoate (I) with 2-(2-bromoethyl)-1,3-dioxolane (II) by means of lithium diisopropylamide gives ethyl 4-[3-(1,3-dioxolan-2-yl)propyl]benzoate (III),which is hydrolyzed to ethyl 4-(3-formylpropyl)benzoate (IV).The condensation of (IV) with 1-(2-aminoethyl) cyclohexanol (V) affords the corresponding imine (VI),which is cyclized with methyl thioglycolate (VII) yielding ethyl 4-[3-[3-[2-[1-hydroxycyclohexyl)ethyl]-4-oxo-2-thiazolidinyl]propyl]benzoate (VIII) .The hydrolysis of (VIII) with KOH gives L-644122 as a racemic mixture (IX),which is methylated with MeI and K2CO3 to the corresponding methyl ester (X).Esterification of (X) with (-)-camphanic acid (XI) by means of dicyclohexylcarbodumide in methylene chloride affords the diastereomeric mixture of esters (XII),which is separated into its components by fractionated crystallization in ethyl acetate hexane.Finally,the (+)-diastereomer (XIII) is hydrolyzed with KOH in refluxing toluene containing diclohexyl-18-crown-6.

参考文献标题:L-644122
文献作者:Serradell,M.N.; Castar,J.
参考来源:Drugs Fut 1986,11(5),372


合成路线:The condensation of ethyl 4-methylbenzoate (I) with 2-(2-bromoethyl)-1,3-dioxolane (II) by means of lithium diisopropylamide gives ethyl 4-[3-(1,3-dioxolan-2-yl)propyl]benzoate (III),which is hydrolyzed to ethyl 4-(3-formylpropyl)benzoate (IV).The condensation of (IV) with 1-(2-aminoethyl) cyclohexanol (V) affords the corresponding imine (VI),which is cyclized with methyl thioglycolate (VII) yielding ethyl 4-[3-[3-[2-[1-hydroxycyclohexyl)ethyl]-4-oxo-2-thiazolidinyl]propyl]benzoate (VIII) .The hydrolysis of (VIII) with KOH gives L-644122 as a racemic mixture (IX),which is methylated with MeI and K2CO3 to the corresponding methyl ester (X).Esterification of (X) with (-)-camphanic acid (XI) by means of dicyclohexylcarbodumide in methylene chloride affords the diastereomeric mixture of esters (XII),which is separated into its components by fractionated crystallization in ethyl acetate hexane.Finally,the (+)-diastereomer (XIII) is hydrolyzed with KOH in refluxing toluene containing diclohexyl-18-crown-6.
参考文献标题:Prostaglandin isosteres.2.Chain-modified thiazolidinone prostaglandin analogues as renal vasodilators.
文献作者:Bicking,J.B.; Bock,M.G.; Cragoe,E.J.Jr.; DiPardo,R.M.; Gould,N.P.; Holtz,W.J.; Lee,T.J.; Robb,C.M.; Smith,R.L.; Springer,J.P.; Blaine,E.H.
参考来源:J Med Chem 1983,26(3),342-348