新产品编号:198259

合成路线:2-Chloro-4-propionylpyridine (I) was protected as the cyclic ketal (II) with 1,3-propanediol and p-toluenesulfonic acid in refluxing toluene with azeotropical removal of water.Subsequent halogen displacement in (II) with sodium methoxide in boiling acetonitrile gave methoxypyridine (III).Lithiation of (III) with mesityllithium,followed by condensation with dimethylformamide provided formylpyridine (IV),which was reduced to alcohol (V) using NaBH4 in MeOH.The hydroxyl group of (V) was protected as the benzyl ether (VI),and the ketal group was then hydrolyzed to ketone (VII) with aqueous trifluoroacetic acid.Reformatskii reaction of (VII) with tert-butyl bromoacetate and zinc afforded the beta-hydroxyester (VIII).Further hydrogenolysis of benzyl ether of (VIII) over Pd/C gave alcohol (IX).Then,treatment of (IX) with trifluoroacetic acid produced lactone (X),and hydrolysis of the methoxy group of (X) with aqueous HCl furnished pyridone (XI).Condensation of 3,4-difluoroacetanilide (XII) with Vilsmeier reagent yielded quinolinecarboxaldehyde (XIII),which was reduced to alcohol (XIV) with NaBH4.This was then coupled with pyridone (XI) under Mitsunobu conditions to give (XV).Finally,Heck reaction of (XV) with palladium acetate and triphenyl phosphine generated the target pentacyclic compound.

参考文献标题:Pro-drugs and counterparts of camptothecin,their application as medicines
文献作者:Lanco,C.; Rolland,A.; Bigg,D.; Lavergne,O.; Harnett,J.; Liberatore,A.-M.(SCRAS (Societ?de Conseils de Recherches et d'Applications Scientifiques))
参考来源:EP 0946566; WO 9828304


合成路线:2-Chloro-4-propionylpyridine (I) was protected as the cyclic ketal (II) with 1,3-propanediol and p-toluenesulfonic acid in refluxing toluene with azeotropical removal of water.Subsequent halogen displacement in (II) with sodium methoxide in boiling acetonitrile gave methoxypyridine (III).Lithiation of (III) with mesityllithium,followed by condensation with dimethylformamide provided formylpyridine (IV),which was reduced to alcohol (V) using NaBH4 in MeOH.The hydroxyl group of (V) was protected as the benzyl ether (VI),and the ketal group was then hydrolyzed to ketone (VII) with aqueous trifluoroacetic acid.Reformatskii reaction of (VII) with tert-butyl bromoacetate and zinc afforded the beta-hydroxyester (VIII).Further hydrogenolysis of benzyl ether of (VIII) over Pd/C gave alcohol (IX).Then,treatment of (IX) with trifluoroacetic acid produced lactone (X),and hydrolysis of the methoxy group of (X) with aqueous HCl furnished pyridone (XI).Condensation of 3,4-difluoroacetanilide (XII) with Vilsmeier reagent yielded quinolinecarboxaldehyde (XIII),which was reduced to alcohol (XIV) with NaBH4.This was then coupled with pyridone (XI) under Mitsunobu conditions to give (XV).Finally,Heck reaction of (XV) with palladium acetate and triphenyl phosphine generated the target pentacyclic compound.
参考文献标题:Homocamptothecins: Synthesis and antitumor activity of novel E-ring-modified camptothecin analogues
文献作者:Lavergne,O.; Lesuer-Ginot,L.; Pla Rodas,F.; Kasprzyk,P.G.; Pommier,J.; Demarquay,D.; Prevost,G.; Ulibarri,G.; Rolland,A.; Schiano-Liberatore,A.M.; Harnett,J.; Pons,D.; Camara,J.; Bigg,D.C.
参考来源:J Med Chem 1998,41(27),5410


产品链接: CAS No. 186668-70-2››