合成路线:Three partial syntheses of Taxol are described starting from Taxol analogues such as Taxol C or Taxol B (cephalomannine):1) The reaction of Taxol C (I) with triethylsilyl chloride (TES-Cl) in pyridine gives the bis(triethylsilyl) derivative (II),which by reduction with zirconocene chloride hydride [bis(cyclopentadienyl)zirconium chloride hydride] in dry THF yields compound (III).The hydrolytic cleavage of (III) with simultaneous desilylation by means of HCl in ethanol affords [2aR-[2aalpha,4beta,4abeta,6beta,9alpha(2R,3S),11beta,12alpha,12aalpha,12balpha]]-6,12b-diacetoxy-9-(3-amino-2-hydroxy-3-phenylpropionyloxy)-1 2-benzoyloxy-4,11-dihydroxy-4a,8,13,13-tetramethyl-2a,3,4,4a,5,6,9,10,11,12,12a,12b-dodecahydro-1H-7,11-methanocyclodeca[3,4]benz[1,2-b]oxet-5-one (IV) with a free amino group,which is benzoylated with benzoyl chloride (V) and pyridine to Taxol.
合成路线:2) The silylation of Taxol B (VI) with triethylsilyl chloride as before gives the bis(triethylsilyl) compound (VII),which by reduction with zirconocene chloride hydride as described yields compound (VIII).Finally,the hydrolytic cleavage of (VIII) with simultaneous desilylation with HCl in ethanol affords the previously reported compound (IV) with its free amino group easily benzoylated to Taxol.3) The ozonolysis of the silylated Taxol B (VII) with O3 in methanol gives compound (IX),which is reduced with zirconocene as before yielding the 2-oxopropylideneimine (X).Finally,the hydrolytic cleavage of (X) with simultaneous desilylation with HCl in ethanol affords the previously reported compound (IX) with its free amino group easiely benzoylated to Taxol.
合成路线:Several partial syntheses of docetaxel have been described:The selective hydrolysis of Taxol A (I,R = Ph),Taxol B (I,R = C(Me)=CHMe) or Taxol C (I,R = C5H11) with NaHCO3 in THF/water gives the corresponding 10-deacetyl derivatives (II),which by selective silylation with triethylsilyl chloride in pyridine are converted into the 10-deacetyl-2',7-bis(triethylsilyl) compounds (III).The reaction of compounds (III) with zirconocene chloride hydride [bis(cyclopentadienyl)zirconium chloride hydride] in THF afford the corresponding imino derivatives (IV),which,without isolation are hydrolyzed and desilylated by a treatment with concentrated aqueous HCl in ethanol giving 10-deacetyltaxolamine (V).Finally,this compound is acylated at the amino group by a treatment by di-tert-butyl dicarbonate and NaHCO3 in ethyl acetate/water.
参考文献标题:Preparation of Taxol and docetaxel through primary amines
文献作者:Young,T.H.(Hauser,Inc.)
参考来源:EP 0852581; WO 9623780
合成路线:The acylation of 10-deacetylbaccatin III (I) with CDI in chloroform gives the 7,10-bis-O-(imidazolylcarbonyl) derivative (II),which is condensed with the chiral oxazolidinecarboxylic acid (III) by means of DCC and DMAP in hot toluene to yield the corresponding ester (IV).The hydrolysis of (IV) with aqueous TFA affords compound (V),which is finally treated with (Boc)2O and NaHCO3 in THF to provide the target docetaxel.
参考文献标题:An improved process for the preparation of docetaxel
文献作者:Duvvuri,S.; Puranik,R.(Dr.Reddy's Research Foundation)
参考来源:WO 0212216
合成路线:Docetaxel is a synthetic derivative of 10-deacetylbaccatin III (10-DAB; RP 61387).The crystalline active ingredient is synthesized by a sequence of more than 10 chemical steps.The optically active side-chain (RPR 108278) is first fully synthesized and coupled with suitably protected 10-DAB.The resulting intermediate is then deprotected to give docetaxel which is crystallized.
参考文献标题:Docetaxel
文献作者:Locci-Tonelli,D.; Spiridonidis,C.H.; Fabre,J.L.
参考来源:Drugs Fut 1995,20(5),464
合成路线:A new method for the synthesis of paclitaxel side chain has been developed: The esterification of (S)-phenylglycine (I) with SOCl2 and methanol gives the corresponding methyl ester (II),which is acylated with benzoyl chloride and pyridine to the benzoyl derivative (III).The reduction of (III) with dibutylaluminum hydride (DIBAL) in toluene yields the corresponding aldehyde (IV),which is condensed with 2-(trimethylsilyl)thiazole (V) by means of tetrabutylammonium fluoride (TBAF) to afford the (1R,2S)-N-[2-hydroxy-1-phenyl-2-(2-thiazolyl)ethyl]benzamide (VI) with a 95% enantiomeric purity.The cyclization of (VI) with 2,2-dimethoxypropane (VII) catalyzed by camphosulfonic acid (CSA) gives (4S,5R)-3-benzoyl-2,2-dimethyl-4-phenyl-5-(2-thiazolyl)oxazolidine (VIII),which is treated with methyl trifluoromethanesulfonate to afford (4S,5R)-3-benzoyl-2,2-dimethyl-4-phenyloxazolidine-5-carbaldehyde (IX).Finally,this compound is oxidized with KMnO4 in tert-butanol/aqueous potassium phosphate buffer to yield (4S,5R)-3-benzoyl-2,2-dimethyl-4-phenyloxazolidine-5-carboxylic acid (X),the side chain of paclitaxel suitably protected.
合成路线:A new method for the synthesis of the docetaxel side-chain has been reported:The esterification of (S)-phenylglycine (I) with SOCl2 and methanol gives the corresponding methyl ester (II),which is acylated with tert-butoxycarbonyl anhydride to the tert-butoxycarbonyl derivative (III).The reduction of (III) with dibutylaluminum hydride (DIBAL) in toluene yields the corresponding aldehyde (IV),which is condensed with 2-(trimethylsilyl)thiazole (V) by means of tetrabutylammonium fluoride (TBAF) to afford the (1R,2S)-N-[2-hydroxy-1-phenyl-2-(2-thiazolyl)ethyl]carbamic acid tert-butyl ester (VI) with 88% enantiomeric purity.The cyclization of (VI) with 2,2-dimethoxypropane (VII) catalyzed by camphosulfonic acid (CSA) gives (4S,5R)-3-(tert-butoxycarbonyl)-2,3-dimethyl-4-phenyl-5-(2-thiazolyl)ox azolidine (VIII),which is treated with methyl trifluoromethanesulfonate to afford (4S,5R)-3-(tert-butoxycarbonyl)-2,2-dimethyl-4-phenyloxazolidine-5-carb aldehyde (IX).Finally,this compound is oxidized with KMnO4 in tert-butanol/aqueous potassium phosphate buffer to yield the corresponding carboxylic acid,the (4S,5R)-3-(tert-butoxycarbonyl)-2,2-dimethyl-4-phenyloxazolidine-5-carb oxylic acid (X),the side-chain of taxotere suitably protected.
参考文献标题:Synthesis of Taxol and Taxotere side chains by 2-(trimethylsilyl)thiazole based homologation of L-phenylglycine
文献作者:Semola,T.; Dondoni,A.; Perrone,D.
参考来源:Synthesis 1995,2(2),181
合成路线:A new synthesis of docetaxel has been developed:The stereoselective dihydroxylation of methyl cinnamate (I) by the Sharpless AD process gives the enantiopure diol (II),which was treated first with tosyl chloride/triethylamine and then with K2CO3 in DMF yielding epoxide (III).Hydrolysis of the ester group of (III) with LiOH in methanol/water affords the epoxy-acid (IV),which is coupled with 7,10-bis(2,2,2-trichloroethoxycarbonyl)-10-deacetylbaccatin III (V) by means of dicyclohexylcarbodiimide (CDD) and dimethylaminopyridine in hot toluene to give the ester (VI).Regioselective cleavage of the epoxide ring of (VI) with NaN3 in aqueous methanol yielded the azide derivative (VII),which was treated with triphenylphosphine in the presence of tert-butoxycarbonyl anhydride and K2CO3 in dichloromethane affording the tert-butoxycarbonylamino derivative (VIII).Finally,(VIII) was submitted to a reductive deprotection with zinc powder in acetic acid.
参考文献标题:Synthesis of taxoids 3.A novel and efficient method for preparation of taxoids employing cis-glycidic acid
文献作者:Harada,N.; Yamaguchi,T.; Hashiyama,T.; Ozaki,K.
参考来源:Tetrahedron Lett 1998,395575
产品链接: CAS No. 114977-28-5›› 产品链接: CAS No.148408-66-6››