合成路线:The title compound was prepared starting from the known bicyclic lactone (VI).Oxidation of the primary alcohol function of (VI) to the corresponding aldehyde (VII) was accomplished by either following the Pfitzner-Moffat method or by means of Dess-Martin perodinane reagent.Aldehyde (VII) was then converted to enone (IX) by Wittig reaction with the phosphonium salt (VIII) or,in a related method,by Wadsworth-Emmons condensation of (VII) with phosphonate (IV).Stereoselective reduction of enone (IX) with either L-selectride or (-)-B-chlorodiisopinocampheylborane produced the (15S)-allylic alcohol (X) as the major diastereoisomer,which was isolated by flash chromatography.Then,catalytic hydrogenation of the double bond of (X) gave the saturated alcohol (XI).Reduction of the lactone function employing DIBAL led to the protected lactol (XII).Subsequent removal of the phenylbenzoyl group of (XII) with K2CO3 in methanol furnished dihydroxy lactol (XIII).In a variation of this sequence,the phenylbenzoyl group of (XI) was first removed by methanolysis,and the resultant dihydroxy lactone (XIV) was then reduced with DIBAL to lactol (XIII).
合成路线:Wittig condensation of lactol (XIII) with (carboxybutyl)triphenylphosphonium bromide (XV) in the presence of potassium tert-butoxide produced the Z-olefin (XVI).Conversion of carboxylic acid (XVI) to the title isopropyl ester was then accomplished by alkylation with 2-iodopropane in the presence of DBU.
参考文献标题:Chemical process
文献作者:Kov醕s,G.; Hermecz,I.; Szab? T.; Ivanics,J.; Dalmadi,G.; Bahram,R.(Chinoin Pharmaceutical and Chemical Works Co.,Ltd.)
参考来源:WO 9300329
合成路线:In an alternative method,the aldehyde lactone (XXIII) was subjected to Wadsworth-Emmons reaction with phosphonate (IV) to afford enone (XXIV).Stereoselective ketone reduction,followed by catalytic hydrogenation of the resultant allylic alcohol (XXV),provided (XXVI).Both the benzoate ester and the lactone groups of (XXIV) were hydrolyzed by KOH,yielding trihydroxy acid (XXVII),which was further cyclized to lactone (XIV) in boiling toluene.The hydroxyl groups of (XIV) were then protected with ethyl vinyl ether in the presence of trichloroacetic acid to produce the bis-acetal (XXVIII).Reduction of the lactone function of (XXVIII) to the corresponding lactol (XXIX),followed by Wittig reaction with the phosphorane generated from phosphonium salt (XV) and potassium t-butoxide,furnished olefin (XXX).After acidic hydrolysis of the acetal protecting groups of (XXX),the carboxylate function was converted to the corresponding isopropyl ester by treatment with 2-iodopropane and cesium carbonate.
参考文献标题:Process and intermediates to prepare latanoprost
文献作者:Henegar,K.E.(Pharmacia Corp.)
参考来源:WO 0187816
合成路线:The required phosphonate reagent (IV) was prepared by two alternative methods.Bromination of benzylacetone (I) in cold methanol afforded 1-bromo-4-phenyl-2-butanone (II).Subsequent displacement of the bromide ion of (II) with NaI in acetone led to the iodo ketone (III).The desired phosphonate (IV) was then obtained by the Arbuzov reaction of (III) with trimethyl phosphite.Alternatively,alkylation of the dianion of dimethyl 2-oxopropyl phosphonate (V) with benzyl bromide led to phosphonate (IV).
合成路线:The title compound was prepared starting from the known bicyclic lactone (VI).Oxidation of the primary alcohol function of (VI) to the corresponding aldehyde (VII) was accomplished by either following the Pfitzner-Moffat method or by means of Dess-Martin perodinane reagent.Aldehyde (VII) was then converted to enone (IX) by Wittig reaction with the phosphonium salt (VIII) or,in a related method,by Wadsworth-Emmons condensation of (VII) with phosphonate (IV).Stereoselective reduction of enone (IX) with either L-selectride or (-)-B-chlorodiisopinocampheylborane produced the (15S)-allylic alcohol (X) as the major diastereoisomer,which was isolated by flash chromatography.Then,catalytic hydrogenation of the double bond of (X) gave the saturated alcohol (XI).Reduction of the lactone function employing DIBAL led to the protected lactol (XII).Subsequent removal of the phenylbenzoyl group of (XII) with K2CO3 in methanol furnished dihydroxy lactol (XIII).In a variation of this sequence,the phenylbenzoyl group of (XI) was first removed by methanolysis,and the resultant dihydroxy lactone (XIV) was then reduced with DIBAL to lactol (XIII).
合成路线:Wittig condensation of lactol (XIII) with (carboxybutyl)triphenylphosphonium bromide (XV) in the presence of potassium tert-butoxide produced the Z-olefin (XVI).Conversion of carboxylic acid (XVI) to the title isopropyl ester was then accomplished by alkylation with 2-iodopropane in the presence of DBU.
参考文献标题:Phenyl-substituted prostaglandins: Potent and selective antiglaucoma agents
文献作者:Resul,B.; Stjernschantz,J.; No,K.T.; Liljebris,C.; Selen,G.; Astin,M.; Karlsson,M.; Bito,L.Z.
参考来源:J Med Chem 1993,36(2),243
产品链接: CAS No. 130209-82-4››