合成路线:1) The cyclization of phloroglucinol (I) with butyrylacetic acid ethyl ester (II) by means of concentrated sulfuric acid gives 5,7-dihydroxy-4-propyl-2H-1-benzopyran-2-one (III),which is condensed with propionyl chloride by means of AlCl3 in nitrobenzene,yielding the 8-propionyl derivative (V).The cyclization of (V) with 3-hydroxy-3-methylbuytyraldehyde dimethylacetal (VI) in refluxing pyridine affords the benzodipyran (VII),which is cyclized again with paraldehyde or acetaldehyde dimethylacetal by means of p-toluenesulfonic acid and trifluoroacetic acid in pyridine at 140 C to give a mixture of the diastereomeric racemates (VIII) and (IX),which are separated by column chromatography.The reduction of racemate (VIII) with NaBH4 /CeCl3 in ethanol yields a new mixture of the racemic hydroxy epimers (X) (racemic calanolide A) and (XI),which are separated by semipreparative HPLC.Racemic calanolide A (X) is finally submitted to optical resolution by semipreparative chiral HPLC.
参考文献标题:Method for the preparation of (+)-calanolide A and
文献作者:Brankovic,D.; Flavin,M.T.; Vilaychack,V.; Liao,S.; Zembower,D.; Lin,L.; Dzekhster,S.; Rizzo,J.D.; Mar,A.; Xu,Z.-Q.; Khilevich,A.; Liu,J.(MediChem Research,Inc.)
参考来源:WO 9838193
合成路线:2) The condensation of 5,7-dihydroxy-4-propyl-2H-1-benzopyran-2-one (III) with N-methylformanilide (XII) by means of POCl3 in hot dichloromethane gives the carbaldehyde (XIII),which is cyclized with 3-chloro-3-methyl-1-butyne (XIV) by means of ZnCl2 /K2CO3 in hot 2-butanone/DMF,yielding the benzodipyran-carbaldehyde (XV).The enantioselective reaction of (XV) with 2(E)-butene and the chiral borane (+)-(E)-crotyldiisopinocamphenylborane (XVI) affords the single (R,R)-enatiomer (XVII).The selective silylation of (XVII) with TBDMS-Cl as usual gives the monosilyl ether (XVIII),which is cyclized by means of mercuric acetate and NaBH4 in THF,yielding the silylated (10R,11R,12R)-benzotripyran (XIX).The desilylation of (XIX) with tetrabutylammonium fluoride in THF gives the (10R,11S,12R)-benzotripyran (XX) (calanolide B),which is converted into calanolide A by inversion of the C-12 OH-group carried out with a modified Mitsunobu reaction with dimethyl azodicarboxylate (DEAD)/trimethylphosphine/chloroacetic acid in toluene/THF,followed by treatment with NH4OH in methanol.
参考文献标题:Synthesis of optically active calanolides A and B
文献作者:Tagliaferri,F.; Yan,S.; Deshpande,P.P.; Baker,D.C.; Victory,S.F.(University of Tennessee,Knoxville)
参考来源:US 5608085; WO 9626934
合成路线:The cyclization of phloroglucinol (I) with 3-oxohexanoic acid methyl ester (II) by means of conc.sulfuric acid gives the benzopyranone (III),which is acylated with 2-methyl-2-butenoyl chloride (IV) and AlCl3 in dichloroethane to yield the 5-hydroxy-7-(2-methyl-2-butenoyloxy)-4-propylbenzopyran-2-one (V).This compound,without isolation,rearranges under the reaction conditions to afford 5,7-dihydroxy-8-(2-methyl-2-butenoyloxy)-4-propylbenzopyran-2-one (VI).The cyclization of (VI) with 3-methyl-2-butenal (VII) in refluxing pyridine provides the benzo-tripyran-2,12-dione derivative (VIII) -alternatively,conversion of (VI) into (VIII) can be performed by first cyclization of (VI) by means of TEA to furnish compound (IX),which is then subjected to cyclization with 3-methyl-2-butenal (VII)-.Finally,reduction of (VIII) with LiAlH(OBu)3 in THF provides the target calanolide A.
参考文献标题:Processes for preparing calanolide A and intermediates thereof
文献作者:Terashima,S.; Koyakumaru,K.(Kuraray Co.,Ltd.; Sagami Chemical Research Center)
参考来源:JP 2002193971; WO 0251847
合成路线:1) The cyclization of phloroglucinol (I) with butyrylacetic acid ethyl ester (II) by means of concentrated sulfuric acid gives 5,7-dihydroxy-4-propyl-2H-1-benzopyran-2-one (III),which is condensed with propionyl chloride by means of AlCl3 in nitrobenzene,yielding the 8-propionyl derivative (V).The cyclization of (V) with 3-hydroxy-3-methylbuytyraldehyde dimethylacetal (VI) in refluxing pyridine affords the benzodipyran (VII),which is cyclized again with paraldehyde or acetaldehyde dimethylacetal by means of p-toluenesulfonic acid and trifluoroacetic acid in pyridine at 140 C to give a mixture of the diastereomeric racemates (VIII) and (IX),which are separated by column chromatography.The reduction of racemate (VIII) with NaBH4 /CeCl3 in ethanol yields a new mixture of the racemic hydroxy epimers (X) (racemic calanolide A) and (XI),which are separated by semipreparative HPLC.Racemic calanolide A (X) is finally submitted to optical resolution by semipreparative chiral HPLC.
参考文献标题:The calanolides,a novel HIV-inhibitory class of c
文献作者:Kashman,Y.; Gustafson,K.R.; Fuller,R.W.; Cardellina,J.H.II; McMahon,J.B.; Currens,M.J.; Buckheit,R.W.Jr.; Hughes,S.H.; Cragg,G.M.; Boyd,M.R.
参考来源:J Med Chem 1992,35(15),2735
合成路线:1) The cyclization of phloroglucinol (I) with butyrylacetic acid ethyl ester (II) by means of concentrated sulfuric acid gives 5,7-dihydroxy-4-propyl-2H-1-benzopyran-2-one (III),which is condensed with propionyl chloride by means of AlCl3 in nitrobenzene,yielding the 8-propionyl derivative (V).The cyclization of (V) with 3-hydroxy-3-methylbuytyraldehyde dimethylacetal (VI) in refluxing pyridine affords the benzodipyran (VII),which is cyclized again with paraldehyde or acetaldehyde dimethylacetal by means of p-toluenesulfonic acid and trifluoroacetic acid in pyridine at 140 C to give a mixture of the diastereomeric racemates (VIII) and (IX),which are separated by column chromatography.The reduction of racemate (VIII) with NaBH4 /CeCl3 in ethanol yields a new mixture of the racemic hydroxy epimers (X) (racemic calanolide A) and (XI),which are separated by semipreparative HPLC.Racemic calanolide A (X) is finally submitted to optical resolution by semipreparative chiral HPLC.
参考文献标题:Novel approach for synthesis of (?-calanolide A a
文献作者:Flavin,M.T.; Sheinkman,A.K.; Boulanger,W.A.; Khilevich,A.; Shone,R.L.; Rizzo,J.D.; Xu,Z.-Q.; Kucherenko,A.
参考来源:Tetrahedron Lett 1995,36(31),5475
合成路线:1) The cyclization of phloroglucinol (I) with butyrylacetic acid ethyl ester (II) by means of concentrated sulfuric acid gives 5,7-dihydroxy-4-propyl-2H-1-benzopyran-2-one (III),which is condensed with propionyl chloride by means of AlCl3 in nitrobenzene,yielding the 8-propionyl derivative (V).The cyclization of (V) with 3-hydroxy-3-methylbuytyraldehyde dimethylacetal (VI) in refluxing pyridine affords the benzodipyran (VII),which is cyclized again with paraldehyde or acetaldehyde dimethylacetal by means of p-toluenesulfonic acid and trifluoroacetic acid in pyridine at 140 C to give a mixture of the diastereomeric racemates (VIII) and (IX),which are separated by column chromatography.The reduction of racemate (VIII) with NaBH4 /CeCl3 in ethanol yields a new mixture of the racemic hydroxy epimers (X) (racemic calanolide A) and (XI),which are separated by semipreparative HPLC.Racemic calanolide A (X) is finally submitted to optical resolution by semipreparative chiral HPLC.
参考文献标题:Synthesis,chromatographic resolution,and anti-hu
文献作者:Khilevich,A.; Rizzo,J.D.; Flavin,M.T.; Kucherenko,A.; Sheinkman,A.K.; Vilaychack,V.; Lin,L.S.; Chen,W.; Greenwood,E.M.; Pengsuparp,T.; Pezzuto,J.M.; Hughes,S.H.; Flavin,T.M.; Cibulski,M.; Boulanger,W.A.; Shone,R.L.; Xu,Z.Q.
参考来源:J Med Chem 1996,39(6),1303
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