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【结 构 式】 
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【分子编号】10448 【品名】(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-1,15-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9-[[(2,2,2-trichloroethoxy)carbonyl]oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate 【CA登记号】 |
【 分 子 式 】C34H39Cl3O13 【 分 子 量 】762.03396 【元素组成】C 53.59% H 5.16% Cl 13.96% O 27.29% |
合成路线1
该中间体在本合成路线中的序号：(II)A process for the preparation of taxol has been described: The acylation of baccatin III (I) with 2,2,2-trichloroethyl chloroformate in pyridine yields the chloroformate (II), which is acylated with cinnamic acid (III) by means of oxalyl chloride of dicyclohexylcarbodiimide to the cinnamate (IV). The oxidative addition of tert-butyl N-chlorocarbamate (V) to (IV) by means of OsO4 in water affords the protected amino hydroxyester (VI), which is deprotected with iodotrimethylsilane in acetonitrile to give the free aminoester (VII). The benzoylation of (VII) with benzoyl chloride in pyridine affords the protected N-benzoyl derivative (VIII), which is finally deprotected by treatment with Zn and acetic acid to eliminate the trichloroethoxycarbonyl group.
| 【1】 Colin, M.; Guenard, D.; Gueritte-Voegelein, F.; Potier, P. (Aventis SA); Process for the preparation of taxol and 10-deacetyltaxol. US 4857653 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 10463 | Benzoyl chloride | 98-88-4 | C7H5ClO | 详情 | 详情 | |
| (I) | 10447 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-1,9,15-trihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate | C31H38O11 | 详情 | 详情 | |
| (II) | 10448 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-1,15-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9-[[(2,2,2-trichloroethoxy)carbonyl]oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate | C34H39Cl3O13 | 详情 | 详情 | |
| (III) | 10449 | (Z)-3-Phenyl-2-propenoic acid | 621-82-9 | C9H8O2 | 详情 | 详情 |
| (IV) | 10450 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-15-[[(Z)-3-phenyl-2-propenoyl]oxy]-9-[[(2,2,2-trichloroethoxy)carbonyl]oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate | C43H45Cl3O14 | 详情 | 详情 | |
| (VI) | 10451 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-15-([3-[(tert-butoxycarbonyl)amino]-2-hydroxy-3-phenylpropanoyl]oxy)-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9-[[(2,2,2-trichloroethoxy)carbonyl]oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate | C48H56Cl3NO17 | 详情 | 详情 | |
| (VII) | 10452 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-15-[(3-amino-2-hydroxy-3-phenylpropanoyl)oxy]-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9-[[(2,2,2-trichloroethoxy)carbonyl]oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate | C43H48Cl3NO15 | 详情 | 详情 | |
| (VIII) | 10453 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-15-[[3-(benzoylamino)-2-hydroxy-3-phenylpropanoyl]oxy]-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9-[[(2,2,2-trichloroethoxy)carbonyl]oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate | C50H52Cl3NO16 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(X)3) The condensation of (4S,5R)-3-(bromoacetyl)-4-methyl-5-phenyloxazolidin-2-one (I) with benzaldehyde (II) by means of dibutylboron triflate gives intermediate (III), which by treatment with lithium ethoxide yields (R,R)-3-phenyloxirane-2-carboxylic acid ethyl ester (IV). The reaction of (IV) with sodium azide in ethanol affords the hydroxy ester (V), which is hydrogenated with H2 over Pd/C in ethyl acetate, giving the amino ester (VI). The protection of (VI) with tert-butoxycarbonyl anhydride affords the protected amino ester (VII), which is treated with 2-methoxypropene and pyridinium p-toluenesulfonate to give the oxazolidine (VIII). The hydrolysis of (VIII) with LiOH in ethanol/water yields (4S,5R)-3-(tert-butoxycarbonyl)-2,2-dimethyl-4-phenyloxazolidine-5-carboxylic acid (IX), which is condensed with the protected baccatin III (X) by means of dicyclohexylcarbodiimide (DCC) and DMAP to afford the oxazolidine ester (XI). The treatment of (XI) with formic acid gives the amino ester (XII), which is benzoylated with benzoyl chloride and NaHCO3 to the protected paclitaxel (XIII). Finally, this compound is deprotected by treatment with Zn/acetic acid. (Commercon, A. et al. Tetrahedron Lett 1992, 33(36): 5185).
| 【1】 Guy, R.K.; Nicolaou, K.C.; Dai, W.M.; Chemistry and biology of taxol. Angew Chem. Int Ed Engl 1994, 33, 1, 15. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 63033 | 2-(ethyloxy)-1-propene; ethyl 1-methylethenyl ether | C5H10O | 详情 | 详情 | ||
| (I) | 10544 | (4S,5R)-3-(2-Bromoacetyl)-4-methyl-5-phenyl-1,3-oxazolan-2-one | C12H12BrNO3 | 详情 | 详情 | |
| (II) | 10498 | Benzaldehyde;Benzoic aldehyde;Phenylmethanal | 100-52-7 | C7H6O | 详情 | 详情 |
| (III) | 10545 | (4S,5R)-3-[(2S,3R)-2-Bromo-3-hydroxy-3-phenylpropanoyl]-4-methyl-5-phenyl-1,3-oxazolan-2-one | C19H18BrNO4 | 详情 | 详情 | |
| (IV) | 10546 | ethyl (2R,3R)-3-phenyl-2-oxiranecarboxylate | 121-39-1 | C11H12O3 | 详情 | 详情 |
| (V) | 10547 | ethyl (2R,3S)-3-azido-2-hydroxy-3-phenylpropanoate | C11H13N3O3 | 详情 | 详情 | |
| (VI) | 10548 | ethyl (2R,3S)-3-amino-2-hydroxy-3-phenylpropanoate | C11H15NO3 | 详情 | 详情 | |
| (VII) | 10549 | ethyl (2R,3S)-3-[(tert-butoxycarbonyl)amino]-2-hydroxy-3-phenylpropanoate | C16H23NO5 | 详情 | 详情 | |
| (VIII) | 10550 | 3-(tert-butyl) 5-ethyl (4S,5R)-2,2-dimethyl-4-phenyl-1,3-oxazolidine-3,5-dicarboxylate | C19H27NO5 | 详情 | 详情 | |
| (IX) | 10551 | (4S,5R)-3-(tert-Butoxycarbonyl)-2,2-dimethyl-4-phenyl-1,3-oxazolane-5-carboxylic acid | C17H23NO5 | 详情 | 详情 | |
| (X) | 10448 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-1,15-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9-[[(2,2,2-trichloroethoxy)carbonyl]oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate | C34H39Cl3O13 | 详情 | 详情 | |
| (XI) | 10553 | 5-((1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-2-(benzoyloxy)-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9-[[(2,2,2-trichloroethoxy)carbonyl]oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-15-yl) 3-(tert-butyl) (4S,5R)-2,2-dimethyl-4-phenyl-1,3-oxazolidine-3,5-dicarboxylate | C51H60Cl3NO17 | 详情 | 详情 | |
| (XII) | 10554 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-15-[[(2R,3S)-3-amino-2-hydroxy-3-phenylpropanoyl]oxy]-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9-[[(2,2,2-trichloroethoxy)carbonyl]oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate | C43H48Cl3NO15 | 详情 | 详情 | |
| (XIII) | 10555 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-15-[[(2R,3S)-3-amino-2-hydroxy-3-phenylpropanoyl]oxy]-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9-[[(2,2,2-trichloroethoxy)carbonyl]oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate | C43H48Cl3NO15 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(II)1) The selective protection of baccatin III (I) with 2,2,2-trichloroethoxycarbonyl chloride and Li-HMDS in DMF gives 7-O-(2,2,2-trichloroethoxycarbonyl)baccatin III (II), which is condensed with the chiral oxazolidine (III) by means of DCC and DMAP in toluene affording the 13-O-oxazolidinyl derivative (III). Finally, this compound is submitted to deprotection with Zn/acetic acid and to cleavage of the oxazolidine ring with trifluoroacetic acid/acetic acid.
| 【1】 Gibson, F.S. (Bristol-Myers Squibb Co.); Synthesis of paclitaxel baccatin III by protecting the 7-hydroxyl using a strong base and an electrophile. WO 9945001 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 10447 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-1,9,15-trihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate | C31H38O11 | 详情 | 详情 | |
| (II) | 10448 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-1,15-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9-[[(2,2,2-trichloroethoxy)carbonyl]oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate | C34H39Cl3O13 | 详情 | 详情 | |
| (III) | 10597 | (4S,5R)-2,4-Diphenyl-4,5-dihydro-1,3-oxazole-5-carboxylic acid | C16H13NO3 | 详情 | 详情 | |
| (IV) | 32008 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-2-(benzoyloxy)-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9-[[(2,2,2-trichloroethoxy)carbonyl]oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-15-yl (4S,5R)-2,4-diphenyl-4,5-dihydro-1,3-oxaz | C50H50Cl3NO15 | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(II)4) The selective protection of baccatin III (I) with 2,2,2-trichloroethoxycarbonyl chloride and Li-HMDS in DMF gives 7-O-(2,2,2-trichloroethoxycarbonyl)baccatin III (II), which is condensed with the chiral azetidinone (IX) by means of lithium tert-butoxide or Li-HMDS in THF and the reaction product, without isolation, is treated with trifluoroacetic acid and acetic acid to afford the protected taxol derivative (X). Finally, this compound is deprotected with Zn and acetic acid.
| 【1】 Gibson, F.S. (Bristol-Myers Squibb Co.); Synthesis of paclitaxel baccatin III by protecting the 7-hydroxyl using a strong base and an electrophile. WO 9945001 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 10447 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-1,9,15-trihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate | C31H38O11 | 详情 | 详情 | |
| (II) | 10448 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-1,15-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9-[[(2,2,2-trichloroethoxy)carbonyl]oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate | C34H39Cl3O13 | 详情 | 详情 | |
| (IX) | 32014 | (3R,4S)-1-benzoyl-3-(1-methoxy-1-methylethoxy)-4-phenyl-2-azetidinone | C20H21NO4 | 详情 | 详情 | |
| (X) | 32015 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-15-[[(2R,3S)-3-(benzoylamino)-2-hydroxy-3-phenylpropanoyl]oxy]-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9-[[(2,2,2-trichloroethoxy)carbonyl]oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en | C50H52Cl3NO16 | 详情 | 详情 |
合成路线5
该中间体在本合成路线中的序号：(XLVII)The introduction of a methylene group in (XXXV) by reaction with the Grignard reagent TMSCH2MgCl and Pd(PPh3)3 as catalyst in ethyl ether, affords the trimethylsilylmethyl compound (XXXVI), which is chlorinated with N-chlorosuccinimide (NCS) in methanol and treated with 2-methoxypropene (XXXIII) and PPTS to provide the chloro derivative (XXXVII). Regioselective hydroxylation of (XXXVII) is performed by enolization with LDA, followed by oxidation with MoO5/pyridine in HMPA and final acylation with Ac2O to give the alpha-acetoxy compound (XXXVIII). This acetate (XXXVIII) is isomerized to the corresponding beta-isomer (XXXIX) by heating with a base such as DBN. The dihydroxylation of the exo-methylene moiety of (XXXIX) with OsO4 and pyridine in ethyl ether yields the corresponding dihydroxy compound (XL), which is cyclized with DBU in refluxing toluene in order to form the oxetane ring of (XLI). The removal of the MOP group of (XLI) with PPTS, followed by reprotection with TES-Cl in DMF gives the triethylsilyl ether (XLII). Cleavage of the cyclic benzylidene ketal of (XLII) with H2 over Pd(OH)2, followed by reaction with triphosgene and pyridine yields the cyclic carbonate (XLIII), which is acetylated at the tertiary OH group of with acetic anhydride and DMAP to yield the acetoxy compound (XLIV). Reaction of (XLIV) with phenyl lithium in THF gives the benzoate (XLV), which is selectively desilylated with HF/pyridine and reprotected with 2,2,2-trichloroethyl chloroformate (Troc-Cl) yielding the intermediate (XLVI). Compound (XLVI) is again desilylated with tris(diethylamino)sulfoxonium difluorotrimethylsiliconate (TASF) affording the secondary alcohol (XLVII).
| 【1】 Kashima, H.; Kusama, H.; Hara, R.; Morihira, K.; Nakamura, N.; Kuwajima, I.; Kawahara, S.; Nishimori, T.; Enantioselective total synthesis of (-)-Taxol. J Am Chem Soc 2000, 122, 16, 3811. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XXXIII) | 17354 | isopropenyl methyl ether; 2-methoxy-1-propene | 116-11-0 | C4H8O | 详情 | 详情 |
| (XXXV) | 43864 | (1S,3S,5S,6R,10S,11S,16S)-16-[[tert-butyl(dimethyl)silyl]oxy]-10-(1-methoxy-1-methylethoxy)-11,15,18,18-tetramethyl-12-oxo-3-phenyl-2,4-dioxatetracyclo[12.3.1.0(1,5).0(6,11)]octadeca-7,14-dien-7-yl trifluoromethanesulfonate | C37H53F3O9SSi | 详情 | 详情 | |
| (XXXVI) | 43865 | (1S,3S,5S,6S,10S,11S,16S)-16-[[tert-butyl(dimethyl)silyl]oxy]-10-(1-methoxy-1-methylethoxy)-11,15,18,18-tetramethyl-3-phenyl-7-[(trimethylsilyl)methyl]-2,4-dioxatetracyclo[12.3.1.0(1,5).0(6,11)]octadeca-7,14-dien-12-one | C40H64O6Si2 | 详情 | 详情 | |
| (XXXVII) | 43866 | (1S,3S,5S,6S,8S,10S,11S,16S)-16-[[tert-butyl(dimethyl)silyl]oxy]-8-chloro-10-(1-methoxy-1-methylethoxy)-11,15,18,18-tetramethyl-7-methylene-3-phenyl-2,4-dioxatetracyclo[12.3.1.0(1,5).0(6,11)]octadec-14-en-12-one | C37H55ClO6Si | 详情 | 详情 | |
| (XXXVIII) | 43867 | (1S,3S,5S,6S,8S,10S,11S,13S,16S)-16-[[tert-butyl(dimethyl)silyl]oxy]-8-chloro-10-(1-methoxy-1-methylethoxy)-11,15,18,18-tetramethyl-7-methylene-12-oxo-3-phenyl-2,4-dioxatetracyclo[12.3.1.0(1,5).0(6,11)]octadec-14-en-13-yl acetate | C39H57ClO8Si | 详情 | 详情 | |
| (XXXIX) | 43868 | (1S,3S,5S,6S,8S,10S,11S,13R,16S)-16-[[tert-butyl(dimethyl)silyl]oxy]-8-chloro-10-(1-methoxy-1-methylethoxy)-11,15,18,18-tetramethyl-7-methylene-12-oxo-3-phenyl-2,4-dioxatetracyclo[12.3.1.0(1,5).0(6,11)]octadec-14-en-13-yl acetate | C39H57ClO8Si | 详情 | 详情 | |
| (XL) | 43869 | (1S,3S,5S,6R,7S,8S,10S,11S,13R,16S)-16-[[tert-butyl(dimethyl)silyl]oxy]-8-chloro-7-hydroxy-7-(hydroxymethyl)-10-(1-methoxy-1-methylethoxy)-11,15,18,18-tetramethyl-12-oxo-3-phenyl-2,4-dioxatetracyclo[12.3.1.0(1,5).0(6,11)]octadec-14-en-13-yl acetate | C39H59ClO10Si | 详情 | 详情 | |
| (XLI) | 43870 | (1S,3S,5S,6R,7S,10R,12S,13S,15R,18S)-18-[[tert-butyl(dimethyl)silyl]oxy]-7-hydroxy-12-(1-methoxy-1-methylethoxy)-13,17,20,20-tetramethyl-14-oxo-3-phenyl-2,4,9-trioxapentacyclo[14.3.1.0(1,5).0(6,13).0(7,10)]icos-16-en-15-yl acetate | C39H58O10Si | 详情 | 详情 | |
| (XLII) | 43871 | (1S,3S,5S,6R,7S,10R,12S,13S,15R,18S)-18-[[tert-butyl(dimethyl)silyl]oxy]-7-hydroxy-13,17,20,20-tetramethyl-14-oxo-3-phenyl-12-[(triethylsilyl)oxy]-2,4,9-trioxapentacyclo[14.3.1.0(1,5).0(6,13).0(7,10)]icos-16-en-15-yl acetate | C41H64O9Si2 | 详情 | 详情 | |
| (XLIII) | 43872 | (1S,5S,6R,7S,10R,12S,13S,15R,18S)-18-[[tert-butyl(dimethyl)silyl]oxy]-7-hydroxy-13,17,20,20-tetramethyl-3,14-dioxo-12-[(triethylsilyl)oxy]-2,4,9-trioxapentacyclo[14.3.1.0(1,5).0(6,13).0(7,10)]icos-16-en-15-yl acetate | C35H58O10Si2 | 详情 | 详情 | |
| (XLIV) | 43873 | (1S,5S,6R,10R,12S,13S,15R,18S)-15-(acetoxy)-18-[[tert-butyl(dimethyl)silyl]oxy]-13,17,20,20-tetramethyl-3,14-dioxo-12-[(triethylsilyl)oxy]-2,4,9-trioxapentacyclo[14.3.1.0(1,5).0(6,13).0(7,10)]icos-16-en-7-yl acetate | C37H60O11Si2 | 详情 | 详情 | |
| (XLV) | 43874 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-15-[[tert-butyl(dimethyl)silyl]oxy]-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate | C43H66O11Si2 | 详情 | 详情 | |
| (XLVI) | 43875 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-15-[[tert-butyl(dimethyl)silyl]oxy]-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9-[[(2,2,2-trichloroethoxy)carbonyl]oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate | C40H53Cl3O13Si | 详情 | 详情 | |
| (XLVII) | 10448 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-1,15-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9-[[(2,2,2-trichloroethoxy)carbonyl]oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate | C34H39Cl3O13 | 详情 | 详情 |
合成路线6
该中间体在本合成路线中的序号：(XLVII)Condensation of (XLVII) with the chiral azetidinone (XLVIII) by means of LiHMDS in THF provides the protected paclitaxel precursor (LIX), which is finally deprotected with Zn in HOAc/water.
| 【1】 Kashima, H.; Kusama, H.; Hara, R.; Morihira, K.; Nakamura, N.; Kuwajima, I.; Kawahara, S.; Nishimori, T.; Enantioselective total synthesis of (-)-Taxol. J Am Chem Soc 2000, 122, 16, 3811. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XLVII) | 10448 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-1,15-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9-[[(2,2,2-trichloroethoxy)carbonyl]oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate | C34H39Cl3O13 | 详情 | 详情 | |
| (XLVIII) | 10490 | (3R,4S)-1-Benzoyl-4-phenyl-3-[(triethylsilyl)oxy]-2-azetanone | C22H27NO3Si | 详情 | 详情 | |
| (XLIX) | 43876 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-15-([(2R,3S)-3-(benzoylamino)-3-phenyl-2-[(triethylsilyl)oxy]propanoyl]oxy)-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9-[[(2,2,2-trichloroethoxy)carbonyl]oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]h | C56H66Cl3NO16Si | 详情 | 详情 |
合成路线7
该中间体在本合成路线中的序号：(VIII)The reaction of (2R,3S)-phenylisoserine (I) with 2-propynyl chloroformate (II) in aq. NaHCO3 gives the N-acylated compound (III), which is treated with diazomethane in ethyl ether (CDI and methanol) to yield the corresponding methyl ester (IV). The reaction of (IV) with 2-methoxypropene (V) and pyridinium p-toluenesulfonate in toluene affords the oxazolidine (VI), which is treated with LiOH in water to provide the oxazolidine-5-carboxylic acid (VII). The esterification of 7-O-(trichloroethoxycarbonyl)baccatin (VIII) with acid (VII) by means of DCC in toluene gives the corresponding ester (IX), which is treated with ammonium tetrathiomolybdate to cleave the oxazolidine ring and yield the 3-amino-2-hydroxypropionyl ester (X). The reaction of (X) with benzoyl chloride (XI) and NaHCO3 in ethyl acetate affords the expected benzamido derivative (XII), which is finally deprotected by means of Zn and AcOH to afford the target paclitaxel.
| 【1】 Sharma, A.P.; Sarkar, S. (Dabur India Ltd.); Method of preparation of paclitaxel (Taxol) using 3-(alk-2-ynyloxy)carbonyl-5-oxazolidine carboxylic acid. WO 0266448 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 54908 | (2R,3S)-3-amino-2-hydroxy-3-phenylpropanoic acid | 136561-53-0 | C9H11NO3 | 详情 | 详情 |
| (II) | 55690 | Propargyl chloroformate | C4H3ClO2 | 详情 | 详情 | |
| (III) | 55691 | (2R,3S)-2-hydroxy-3-phenyl-3-{[(2-propynyloxy)carbonyl]amino}propanoic acid | C13H13NO5 | 详情 | 详情 | |
| (IV) | 55692 | methyl (2R,3S)-2-hydroxy-3-phenyl-3-{[(2-propynyloxy)carbonyl]amino}propanoate | C14H15NO5 | 详情 | 详情 | |
| (V) | 17354 | isopropenyl methyl ether; 2-methoxy-1-propene | 116-11-0 | C4H8O | 详情 | 详情 |
| (VI) | 55693 | 5-methyl 3-(2-propynyl) (4S,5R)-2,2-dimethyl-4-phenyl-1,3-oxazolidine-3,5-dicarboxylate | C17H19NO5 | 详情 | 详情 | |
| (VII) | 55694 | (4S,5R)-2,2-dimethyl-4-phenyl-3-[(2-propynyloxy)carbonyl]-1,3-oxazolidine-5-carboxylic acid | C16H17NO5 | 详情 | 详情 | |
| (VIII) | 10448 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-1,15-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9-[[(2,2,2-trichloroethoxy)carbonyl]oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate | C34H39Cl3O13 | 详情 | 详情 | |
| (IX) | 55695 | 5-((1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-2-(benzoyloxy)-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9-{[(2,2,2-trichloroethoxy)carbonyl]oxy}-6-oxatetracyclo[11.3.1.0~3,10~.0~4,7~]heptadec-13-en-15-yl) 3-(2-propynyl) (4S,5R)-2,2-dimethyl-4-phenyl-1,3-oxazolidine-3,5-dicarboxylate | C50H54Cl3NO17 | 详情 | 详情 | |
| (X) | 10554 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-15-[[(2R,3S)-3-amino-2-hydroxy-3-phenylpropanoyl]oxy]-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9-[[(2,2,2-trichloroethoxy)carbonyl]oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate | C43H48Cl3NO15 | 详情 | 详情 | |
| (XI) | 10463 | Benzoyl chloride | 98-88-4 | C7H5ClO | 详情 | 详情 |
| (XII) | 55696 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-12-(acetyloxy)-15-{[(2R,3S)-3-(benzoylamino)-2-hydroxy-3-phenylpropanoyl]oxy}-1,4-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9-{[(2,2,2-trichloroethoxy)carbonyl]oxy}-6-oxatetracyclo[11.3.1.0~3,10~.0~4,7~]heptadec-13-en-2-yl benzoate | C48H50Cl3NO15 | 详情 | 详情 |