合成路线:Palladium-catalyzed coupling of 2-bromo-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalene (I) with 2-methyl-3-butyn-2-ol (II) provided adduct (III).Subsequent cleavage of the propargyl alcohol of (III) with KOH in toluene gave the free acetylene (IV).Lithiation of (IV),followed by quenching with ethyl chloroformate,yielded the aryl propiolic ester (V).Conjugate addition to (V) of the in situ-generated lithium dimethylcuprate gave the Z-crotonate (VI),which was further reduced to the allylic alcohol (VII) using DIBAL.Enantioselective Simmons-Smith cyclopropanation in the presence of (+)-diethyl tartrate produced the cyclopropyl alcohols (VIII) in 80% e.e.favoring the (-)-enantiomer.This mixture was converted to the diastereomeric camphenoate esters,which were separated by preparative chromatography.The desired major isomer (IX) was then hydrolyzed to give the enantiomerically pure alcohol (X),and then oxidized to aldehyde (XI) using N-methylmorpholine-N-oxide and tetrapropylammonium perruthenate.
参考文献标题:2,4-Pentadienoic acid derivs.having retinoid-like biological activity
文献作者:Chandraratna,R.A.; Vuligonda,V.(Vision Pharmaceuticals,Inc.)
参考来源:WO 9908992
合成路线:Palladium-catalyzed coupling of 2-bromo-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalene (I) with 2-methyl-3-butyn-2-ol (II) provided adduct (III).Subsequent cleavage of the propargyl alcohol of (III) with KOH in toluene gave the free acetylene (IV).Lithiation of (IV),followed by quenching with ethyl chloroformate,yielded the aryl propiolic ester (V).Conjugate addition to (V) of the in situ-generated lithium dimethylcuprate gave the Z-crotonate (VI),which was further reduced to the allylic alcohol (VII) using DIBAL.Enantioselective Simmons-Smith cyclopropanation in the presence of (+)-diethyl tartrate produced the cyclopropyl alcohols (VIII) in 80% e.e.favoring the (-)-enantiomer.This mixture was converted to the diastereomeric camphenoate esters,which were separated by preparative chromatography.The desired major isomer (IX) was then hydrolyzed to give the enantiomerically pure alcohol (X),and then oxidized to aldehyde (XI) using N-methylmorpholine-N-oxide and tetrapropylammonium perruthenate.
合成路线:Horner-Emmons condensation of aldehyde (XI) with phosphonate (XII) produced the diene ester (XIII).Finally,ethyl ester hydrolysis of (XIII) gave rise to the title carboxylic acid.
参考文献标题:Enantioselective syntheses of potent retinoid X receptor ligands: Differential biological activities of individuals antipodes
文献作者:Vuligonda,V.; Thacher,S.M.; Chandraratna,R.A.
参考来源:J Med Chem 2001,44(14),2298
产品链接: CAS No. 220619-73-8››