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【结 构 式】

【分子编号】50769

【品名】ethyl (2S)-2-[[tert-butyl(dimethyl)silyl]oxy]propanoate

【CA登记号】

【 分 子 式 】C11H24O3Si

【 分 子 量 】232.39526

【元素组成】C 56.85% H 10.41% O 20.65% Si 12.09%

与该中间体有关的原料药合成路线共 2 条

合成路线1

该中间体在本合成路线中的序号:(XXIX)

Protection of ethyl lactate (XXX) with tert-butyldimethylsilyl chloride in DMF in the presence of imidazole provides derivative (XXXI), which is then converted into dipeptide (XXXII) by first hydrolysis with LiOH in THF/H2O followed by coupling with L-proline methyl ester (X) by means of DCC, HOBt and NMM. Next, hydrolysis of the methyl ester of (XXXII) with LiOH in THF/H2O yields carboxylic acid (XXXIII). Esterification of Z-D-N-Me-Leu (XXXIV) with 2-(trimethylsilyl)ethanol (XXXV) by means of EDCI, DMAP and Et3N in DMF furnishes leucine derivative (XXXVI), whose Z protecting group is removed by hydrogenation over Pd/C in MeOH/AcOEt to afford secondary amine (XXXVII). Coupling of carboxylic acid (XXXIII) with amine (XXXVII) is then performed by means of BOPCl, Et3N. Treatment with tetrabutylammonium fluoride in DMF allows protecting group removal to provide carboxylic acid derivative (XXXVIII), which is then attached to macrocycle (XXIX) by means of BOP and NMM in CH2Cl2 to furnish the target didemnin.

1 Li, W.-R.; et al.; Total synthesis and structural investigations of didemnins A, B, and C. J Am Chem Soc 1990, 112, 21, 7659.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(X) 29552 methyl (2S)-2-pyrrolidinecarboxylate 2133-40-6 C6H11NO2 详情 详情
(XXIX) 50769 ethyl (2S)-2-[[tert-butyl(dimethyl)silyl]oxy]propanoate C11H24O3Si 详情 详情
(XXX) 16659 ethyl (2S)-2-hydroxypropanoate; (S)-ethyl lactate 687-47-8 C5H10O3 详情 详情
(XXXI) 50769 ethyl (2S)-2-[[tert-butyl(dimethyl)silyl]oxy]propanoate C11H24O3Si 详情 详情
(XXXII) 50770 methyl (2S)-1-((2S)-2-[[tert-butyl(dimethyl)silyl]oxy]propanoyl)-2-pyrrolidinecarboxylate C15H29NO4Si 详情 详情
(XXXIII) 50771 (2S)-1-((2S)-2-[[tert-butyl(dimethyl)silyl]oxy]propanoyl)-2-pyrrolidinecarboxylic acid C14H27NO4Si 详情 详情
(XXXIV) 50772 (2R)-2-[[(benzyloxy)carbonyl](methyl)amino]-4-methylpentanoic acid C15H21NO4 详情 详情
(XXXV) 20323 2-(trimethylsilyl)-1-ethanol 2916-68-9 C5H14OSi 详情 详情
(XXXVI) 50773 2-(trimethylsilyl)ethyl (2R)-2-[[(benzyloxy)carbonyl](methyl)amino]-4-methylpentanoate C20H33NO4Si 详情 详情
(XXXVII) 50774 2-(trimethylsilyl)ethyl (2R)-4-methyl-2-(methylamino)pentanoate C12H27NO2Si 详情 详情
(XXXVIII) 37840 (2R)-2-[([(2S)-1-[(2S)-2-hydroxypropanoyl]pyrrolidinyl]carbonyl)(methyl)amino]-4-methylpentanoic acid C15H26N2O5 详情 详情

合成路线2

该中间体在本合成路线中的序号:(XXXI)

Protection of ethyl lactate (XXX) with tert-butyldimethylsilyl chloride in DMF in the presence of imidazole provides derivative (XXXI), which is then converted into dipeptide (XXXII) by first hydrolysis with LiOH in THF/H2O followed by coupling with L-proline methyl ester (X) by means of DCC, HOBt and NMM. Next, hydrolysis of the methyl ester of (XXXII) with LiOH in THF/H2O yields carboxylic acid (XXXIII). Esterification of Z-D-N-Me-Leu (XXXIV) with 2-(trimethylsilyl)ethanol (XXXV) by means of EDCI, DMAP and Et3N in DMF furnishes leucine derivative (XXXVI), whose Z protecting group is removed by hydrogenation over Pd/C in MeOH/AcOEt to afford secondary amine (XXXVII). Coupling of carboxylic acid (XXXIII) with amine (XXXVII) is then performed by means of BOPCl, Et3N. Treatment with tetrabutylammonium fluoride in DMF allows protecting group removal to provide carboxylic acid derivative (XXXVIII), which is then attached to macrocycle (XXIX) by means of BOP and NMM in CH2Cl2 to furnish the target didemnin.

1 Li, W.-R.; et al.; Total synthesis and structural investigations of didemnins A, B, and C. J Am Chem Soc 1990, 112, 21, 7659.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(X) 29552 methyl (2S)-2-pyrrolidinecarboxylate 2133-40-6 C6H11NO2 详情 详情
(XXIX) 50769 ethyl (2S)-2-[[tert-butyl(dimethyl)silyl]oxy]propanoate C11H24O3Si 详情 详情
(XXX) 16659 ethyl (2S)-2-hydroxypropanoate; (S)-ethyl lactate 687-47-8 C5H10O3 详情 详情
(XXXI) 50769 ethyl (2S)-2-[[tert-butyl(dimethyl)silyl]oxy]propanoate C11H24O3Si 详情 详情
(XXXII) 50770 methyl (2S)-1-((2S)-2-[[tert-butyl(dimethyl)silyl]oxy]propanoyl)-2-pyrrolidinecarboxylate C15H29NO4Si 详情 详情
(XXXIII) 50771 (2S)-1-((2S)-2-[[tert-butyl(dimethyl)silyl]oxy]propanoyl)-2-pyrrolidinecarboxylic acid C14H27NO4Si 详情 详情
(XXXIV) 50772 (2R)-2-[[(benzyloxy)carbonyl](methyl)amino]-4-methylpentanoic acid C15H21NO4 详情 详情
(XXXV) 20323 2-(trimethylsilyl)-1-ethanol 2916-68-9 C5H14OSi 详情 详情
(XXXVI) 50773 2-(trimethylsilyl)ethyl (2R)-2-[[(benzyloxy)carbonyl](methyl)amino]-4-methylpentanoate C20H33NO4Si 详情 详情
(XXXVII) 50774 2-(trimethylsilyl)ethyl (2R)-4-methyl-2-(methylamino)pentanoate C12H27NO2Si 详情 详情
(XXXVIII) 37840 (2R)-2-[([(2S)-1-[(2S)-2-hydroxypropanoyl]pyrrolidinyl]carbonyl)(methyl)amino]-4-methylpentanoic acid C15H26N2O5 详情 详情
Extended Information