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【结 构 式】

【分子编号】18900

【品名】tert-butyl 2-(tert-butoxy)-2-oxoacetate

【CA登记号】

【 分 子 式 】C10H18O4

【 分 子 量 】202.25052

【元素组成】C 59.39% H 8.97% O 31.64%

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:(III)

Title compound can be prepared either by bacterial fermentation or by chemical synthesis. Thus, the compund was isolated from cultures of Nostoc sp. GSV 224, growing in the presence of 2,2-dimethyl-b-alanine. After lyophilization and extraction with CH3CN-CH2Cl2, the extract was subjected to several chromatographic purifications to provide the pure compound. Alternatively, 2,2-dimethyl-b-alanine tert-butyl ester (I) was deprotected with trifluoroacetic acid, and the resulting carboxylic acid (II) was treated with di tert-butyl oxalate (III) in the presence of NaOH to afford carbamate (IV). Subsequent coupling with allyl (S)-2-hydroxy-4-methylpentanoate (V) using DCC and DMAP gave ester (VI). The allyl ester was then cleaved by treatment with Pd(Ph3P)4 and morpholine in THF at r.t., and the resulting acid (VII) was coupled with compound (VIII) in the presence of DCC and DMAP to afford (IX). After deprotection of the trichloroethyl ester group by treatment with Zn in AcOH and subsequent cleavage of the N-Boc group with trifluoroacetic acid, the resulting amino acid compound (XI) was cyclized using pentafluorophenyl diphenyl phosphinate (FDPP) to furnish (XII). Finally, epoxidation with meta-chloroperbenzoic acid provided a mixture of diastereomeric epoxides that were separated by reverse phase HPLC.

1 Shih, C.; Gossett, L.S.; Gruber, J.M.; Grossman, C.S.; Andis, S.L.; Schultz, R.M.; Worzalla, J.F.; Corbett, T.H.; Metz, J.T.; Synthesis and biological evaluation of novel cryptophycin analogs with modification in the beta-alanine region. Bioorg Med Chem Lett 1999, 9, 1, 69.
2 Moore, R.E.; Patel, V.F.; Ray, J.E.; Toth, J.E. (Eli Lilly and Company; University of Hawaii; Wayne State University); Pharmaceutical cpds.. EP 0850057; JP 2000501067; WO 9707798; WO 9708334 .
3 Shih, C. (Eli Lilly and Company; University of Hawaii; Wayne State University); Pharmaceutical cpds.. EP 0869786; JP 2000502351; WO 9723211 .
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) 18898 tert-butyl 3-amino-2,2-dimethylpropanoate C9H19NO2 详情 详情
(II) 18899 2,2-dimethyl-beta-alanine C5H11NO2 详情 详情
(III) 18900 tert-butyl 2-(tert-butoxy)-2-oxoacetate C10H18O4 详情 详情
(IV) 18901 N-(tert-butoxycarbonyl)-2,2-dimethyl-beta-alanine C10H19NO4 详情 详情
(V) 18902 allyl (2S)-2-hydroxy-4-methylpentanoate C9H16O3 详情 详情
(VI) 18903 allyl (2S)-2-([3-[(tert-butoxycarbonyl)amino]-2,2-dimethylpropanoyl]oxy)-4-methylpentanoate C19H33NO6 详情 详情
(VII) 18904 (2S)-2-([3-[(tert-butoxycarbonyl)amino]-2,2-dimethylpropanoyl]oxy)-4-methylpentanoic acid C16H29NO6 详情 详情
(VIII) 18905 2,2,2-trichloroethyl (2R)-3-(3-chloro-4-methoxyphenyl)-2-[[(2E,5S,6R,7E)-5-hydroxy-6-methyl-8-phenyl-2,7-octadienoyl]amino]propanoate C27H29Cl4NO5 详情 详情
(IX) 18906 2,2,2-trichloroethyl (10S,13S,15E,19R)-19-(3-chloro-4-methoxybenzyl)-10-isobutyl-2,2,7,7-tetramethyl-13-[(1R,2E)-1-methyl-3-phenyl-2-propenyl]-4,8,11,17-tetraoxo-3,9,12-trioxa-5,18-diaza-15-icosen-20-oate C43H56Cl4N2O10 详情 详情
(X) 18907 (10S,13S,15E,19R)-19-(3-chloro-4-methoxybenzyl)-10-isobutyl-2,2,7,7-tetramethyl-13-[(1R,2E)-1-methyl-3-phenyl-2-propenyl]-4,8,11,17-tetraoxo-3,9,12-trioxa-5,18-diaza-15-icosen-20-oic acid C41H55ClN2O10 详情 详情
(XI) 18908 (2R)-2-[[(2E,5S,6R,7E)-5-([(2S)-2-[(3-amino-2,2-dimethylpropanoyl)oxy]-4-methylpentanoyl]oxy)-6-methyl-8-phenyl-2,7-octadienoyl]amino]-3-(3-chloro-4-methoxyphenyl)propionic acid C36H47ClN2O8 详情 详情
(XII) 18909 (3S,10R,16S)-10-(3-chloro-4-methoxybenzyl)-3-isobutyl-6,6-dimethyl-16-[(1R,2E)-1-methyl-3-phenyl-2-propenyl]-1,4-dioxa-8,11-diaza-13-cyclohexadecene-2,5,9,12-tetrone C36H45ClN2O7 详情 详情
Extended Information