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【结 构 式】

【分子编号】35350

【品名】(1S,2S,3S,4S,6R,9S)-6-(acetoxy)-3-(1-[(1R)-1-[(benzyloxy)methoxy]-3-oxopropyl]vinyl)-1-hydroxy-4,8,11,11-tetramethyl-5-oxo-9-[(triisopropylsilyl)oxy]bicyclo[5.3.1]undec-7-en-2-yl benzoate

【CA登记号】

【 分 子 式 】C46H64O10Si

【 分 子 量 】805.09366

【元素组成】C 68.63% H 8.01% O 19.87% Si 3.49%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(XXII)

The Grignard reaction of aldehyde (XVII) with allylmagnesium bromide in presence of ZnCl2, followed by protection of the resulting alcohol with benzyloxymethyl chloride (Bom-Cl) gives the intermediate (XVIII), which by desilylation of NH4F; cleavage of the cyclic carbonate with Ph-Li and acylation of the OH group with Ac2O yields the benzoate ester (XIX). The transposition of the acetoxyketone grouping, catalyzed by the cyclic guanidine (XX) provides (XXI) with the correct stereochemistry of taxol. The ozonolysis of the terminal double bond of (XXI) gives aldehyde (XXII), which is cyclized by means of DMAP in dichloromethane yielding the tricyclic alcohol (XXIII). The protection of the OH group of (XXIII) with 2,2,2-trichloroethyl chloroformate (Troc-Cl) affords the expected carbonate (XXIV), which is treated with NaI and HCl in order to eliminate the Bom protecting group to give the secondary alcohol (XXV). The reaction of (XXV) with Ms-Cl yields the mesylate (XXVI), which by reaction with LiBr is converted into the bromide (XXVII). The oxidation of (XXVII) with OsO4, followed by a treatment with triphosgene affords the glycol (XXVIII), which is cyclized with means of KCN and DIEA and acetylated with Ac2O providing (XXIX) with the oxetane ring of taxol.

1 Wender, P.A.; et al.; The pinene path to taxanes. 6. Concise stereocontrolled synthesis of Taxol. J Am Chem Soc 1997, 119, 11, 2757.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
10386 Allyl(bromo)magnesium 1730-25-2 C3H5BrMg 详情 详情
(XVII) 35345 2-[(1S,5S,6S,7S,8S,12S)-7,11,14,14-tetramethyl-3,9-dioxo-8-[(triethylsilyl)oxy]-12-[(triisopropylsilyl)oxy]-2,4-dioxatricyclo[8.3.1.0(1,5)]tetradec-10-en-6-yl]acrylaldehyde C34H58O7Si2 详情 详情
(XVIII) 35346 (1S,5S,6S,7S,8S,12S)-6-[(2R)-2-[(benzyloxy)methoxy]-1-methylene-4-pentenyl]-7,11,14,14-tetramethyl-8-[(triethylsilyl)oxy]-12-[(triisopropylsilyl)oxy]-2,4-dioxatricyclo[8.3.1.0(1,5)]tetradec-10-ene-3,9-dione C45H72O8Si2 详情 详情
(XIX) 35347   C47H66O9Si 详情 详情
(XX) 35348 1,3,4,6,7,8-hexahydro-2H-pyrimido[1,2-a]pyrimidine C7H13N3 详情 详情
(XXI) 35349 (1S,2S,3S,4S,6R,9S)-6-(acetoxy)-3-[(2R)-2-[(benzyloxy)methoxy]-1-methylene-4-pentenyl]-1-hydroxy-4,8,11,11-tetramethyl-5-oxo-9-[(triisopropylsilyl)oxy]bicyclo[5.3.1]undec-7-en-2-yl benzoate C47H66O9Si 详情 详情
(XXII) 35350 (1S,2S,3S,4S,6R,9S)-6-(acetoxy)-3-(1-[(1R)-1-[(benzyloxy)methoxy]-3-oxopropyl]vinyl)-1-hydroxy-4,8,11,11-tetramethyl-5-oxo-9-[(triisopropylsilyl)oxy]bicyclo[5.3.1]undec-7-en-2-yl benzoate C46H64O10Si 详情 详情
(XXIII) 35351 (1S,2S,3R,5R,7S,8S,10R,13S)-10-(acetoxy)-5-[(benzyloxy)methoxy]-1,7-dihydroxy-8,12,15,15-tetramethyl-4-methylene-9-oxo-13-[(triisopropylsilyl)oxy]tricyclo[9.3.1.0(3,8)]pentadec-11-en-2-yl benzoate C46H64O10Si 详情 详情
(XXIV) 35352 (1S,2S,3R,5R,7S,8S,10R,13S)-10-(acetoxy)-5-[(benzyloxy)methoxy]-1-hydroxy-8,12,15,15-tetramethyl-4-methylene-9-oxo-7-[[(2,2,2-trichloroethoxy)carbonyl]oxy]-13-[(triisopropylsilyl)oxy]tricyclo[9.3.1.0(3,8)]pentadec-11-en-2-yl benzoate C49H65Cl3O12Si 详情 详情
(XXV) 35353 (1S,2S,3R,5R,7S,8S,10R,13S)-10-(acetoxy)-1,5-dihydroxy-8,12,15,15-tetramethyl-4-methylene-9-oxo-7-[[(2,2,2-trichloroethoxy)carbonyl]oxy]-13-[(triisopropylsilyl)oxy]tricyclo[9.3.1.0(3,8)]pentadec-11-en-2-yl benzoate C41H57Cl3O11Si 详情 详情
(XXVI) 35354 (1S,2S,3R,5R,7S,8S,10R,13S)-10-(acetoxy)-1-hydroxy-8,12,15,15-tetramethyl-5-[[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]-4-methylene-9-oxo-7-[[(2,2,2-trichloroethoxy)carbonyl]oxy]-13-[(triisopropylsilyl)oxy]tricyclo[9.3.1.0(3,8)]pentadec-11-en-2- C44H63Cl3O11SSi 详情 详情
(XXVII) 35355 (1S,2S,3S,5S,7S,8S,10R,13S)-10-(acetoxy)-5-bromo-1-hydroxy-8,12,15,15-tetramethyl-4-methylene-9-oxo-7-[[(2,2,2-trichloroethoxy)carbonyl]oxy]-13-[(triisopropylsilyl)oxy]tricyclo[9.3.1.0(3,8)]pentadec-11-en-2-yl benzoate C41H56BrCl3O10Si 详情 详情
(XXVIII) 35356 (1S,5S,6R,7S,8S,10S,11S,13R,16S)-8-bromo-7-hydroxy-7-(hydroxymethyl)-11,15,18,18-tetramethyl-3,12-dioxo-10-[[(2,2,2-trichloroethoxy)carbonyl]oxy]-16-[(triisopropylsilyl)oxy]-2,4-dioxatetracyclo[12.3.1.0(1,5).0(6,11)]octadec-14-en-13-yl acetate C35H52BrCl3O12Si 详情 详情
(XXIX) 35357 (1S,5S,6R,10R,12S,13S,15R,18S)-15-(acetoxy)-13,17,20,20-tetramethyl-3,14-dioxo-12-[[(2,2,2-trichloroethoxy)carbonyl]oxy]-18-[(triisopropylsilyl)oxy]-2,4,9-trioxapentacyclo[14.3.1.0(1,5).0(6,13).0(7,10)]icos-16-en-7-yl acetate C37H53Cl3O13Si 详情 详情
Extended Information