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【结 构 式】

【分子编号】43873

【品名】(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

【CA登记号】

【 分 子 式 】C37H60O11Si2

【 分 子 量 】737.0478

【元素组成】C 60.3% H 8.21% O 23.88% Si 7.62%

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:(XLIV)

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
Extended Information