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【结 构 式】 
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【分子编号】42025 【品名】2-(2-hydroxy-5-methoxyphenyl)-5-methyl-1,3-oxazole-4-carboxylic acid 【CA登记号】 |
【 分 子 式 】C12H11NO5 【 分 子 量 】249.22308 【元素组成】C 57.83% H 4.45% N 5.62% O 32.1% |
合成路线1
该中间体在本合成路线中的序号：(XII)Synthesis of intermediate (XII): The protection of 2-hydroxy-5-methoxybenzoic acid (VI) with benzyl bromide and K2CO3 in DMF gives 2-(benzyloxy)-5-methoxybenzoic acid (VII), which is condensed with L-threonine methyl ester (VIII) by means of (OEt)2P(O)CN (DEPC) and TEA in DMF yielding the corresponding benzamide (IX). The oxidation of (IX) with DMP, followed by cyclization by means of PPh3 and TEA affords 2-[2-(benzyloxy)-5-methoxyphenyl]-5-methyloxazole-4-carboxylic acid methyl ester (X) which is debenzylated with H2 over Pd/C in methanol to the corresponding phenol (XI). Finally the ester group of (XI) is hydrolyzed with NaOH in THF/water to afford the acid intermediate (XII).
| 【1】 Yokokawa, F.; et al.; Total synthesis of amamistatin A, an antiproliferative linear peptide from an actinomycete. Tetrahedron 2000, 56, 19, 3027. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VI) | 42020 | 2-hydroxy-5-methoxybenzoic acid | 2612-02-4 | C8H8O4 | 详情 | 详情 |
| (VII) | 42021 | 2-(benzyloxy)-5-methoxybenzoic acid | C15H14O4 | 详情 | 详情 | |
| (VIII) | 42026 | methyl (2S,3R)-2-amino-3-hydroxybutanoate | C5H11NO3 | 详情 | 详情 | |
| (IX) | 42022 | methyl (2S,3R)-2-[[2-(benzyloxy)-5-methoxybenzoyl]amino]-3-hydroxybutanoate | C20H23NO6 | 详情 | 详情 | |
| (X) | 42023 | methyl 2-[2-(benzyloxy)-5-methoxyphenyl]-5-methyl-1,3-oxazole-4-carboxylate | C20H19NO5 | 详情 | 详情 | |
| (XI) | 42024 | methyl 2-(2-hydroxy-5-methoxyphenyl)-5-methyl-1,3-oxazole-4-carboxylate | C13H13NO5 | 详情 | 详情 | |
| (XII) | 42025 | 2-(2-hydroxy-5-methoxyphenyl)-5-methyl-1,3-oxazole-4-carboxylic acid | C12H11NO5 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XII)Synthesis of the final product: The cyclization of L-lysine (XVII) according to Miller et al. gives cyclic hydroxamate (XVIII), which is deprotected by hydrogenation with H2 over Pd/C in MeOH yielding 3-amino-1-(tert-butyldiphenylsilyloxy)perhydroazepin-2-one (XIX). The condensation of (XIX) with acid intermediate (V) by means of DEPC and TEA in DMF affords the corresponding amide (XX), which is esterified at its free OH group with acid intermediate (XVI) by means of DCC and DMAP in toluene to provide the ester (XXI). The deprotection of (XXI) with H2 over Pd/C in MeOH gives the amine (XXII), which is acylated with acid intermediate (XII) by means of EDC in CH2Cl2 to furnish the corresponding amide (XXIII). Finally this compound is deprotected with trifluoroacetic acid in CH2Cl2 to give the title product.
| 【1】 Miller, M.J.; Hu, J.; Total synthesis of a mycobactin S, a siderophore and growth promoter of Mycobacterium smegmatis, and determination of its growth inhibitory activity against Mycobacterium tuberculosis. J Am Chem Soc 1997, 119, 15, 3462. |
| 【2】 Yokokawa, F.; et al.; Total synthesis of amamistatin A, an antiproliferative linear peptide from an actinomycete. Tetrahedron 2000, 56, 19, 3027. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (V) | 42019 | (3S)-3-hydroxy-2,2-dimethyldecanoic acid | C12H24O3 | 详情 | 详情 | |
| (XII) | 42025 | 2-(2-hydroxy-5-methoxyphenyl)-5-methyl-1,3-oxazole-4-carboxylic acid | C12H11NO5 | 详情 | 详情 | |
| (XVI) | 42030 | (12R)-12-[[(benzyloxy)carbonyl]amino]-8-formyl-2,2-dimethyl-5,7-dioxa-8-aza-2-silatridecan-13-oic acid | C20H32N2O7Si | 详情 | 详情 | |
| (XVII) | 17525 | (2S)-6-amino-2-[[(benzyloxy)carbonyl]amino]hexanoic acid | C14H20N2O4 | 详情 | 详情 | |
| (XVIII) | 42031 | benzyl (3S)-1-[[tert-butyl(diphenyl)silyl]oxy]-2-oxoazepanylcarbamate | C30H36N2O4Si | 详情 | 详情 | |
| (XIX) | 42032 | (3S)-3-amino-1-[[tert-butyl(diphenyl)silyl]oxy]-2-azepanone | C22H30N2O2Si | 详情 | 详情 | |
| (XX) | 42033 | (3S)-N-((3S)-1-[[tert-butyl(diphenyl)silyl]oxy]-2-oxoazepanyl)-3-hydroxy-2,2-dimethyldecanamide | C34H52N2O4Si | 详情 | 详情 | |
| (XXI) | 42034 | (1S)-1-[2-[((3S)-1-[[tert-butyl(diphenyl)silyl]oxy]-2-oxoazepanyl)amino]-1,1-dimethyl-2-oxoethyl]octyl (12R)-12-[[(benzyloxy)carbonyl]amino]-8-formyl-2,2-dimethyl-5,7-dioxa-8-aza-2-silatridecan-13-oate | C54H82N4O10Si2 | 详情 | 详情 | |
| (XXII) | 42035 | (1S)-1-[2-[((3S)-1-[[tert-butyl(diphenyl)silyl]oxy]-2-oxoazepanyl)amino]-1,1-dimethyl-2-oxoethyl]octyl (12R)-12-amino-8-formyl-2,2-dimethyl-5,7-dioxa-8-aza-2-silatridecan-13-oate | C46H76N4O8Si2 | 详情 | 详情 | |
| (XXIII) | 42036 | (1S)-1-[2-[((3S)-1-[[tert-butyl(diphenyl)silyl]oxy]-2-oxoazepanyl)amino]-1,1-dimethyl-2-oxoethyl]octyl (12R)-8-formyl-12-([[2-(2-hydroxy-5-methoxyphenyl)-5-methyl-1,3-oxazol-4-yl]carbonyl]amino)-2,2-dimethyl-5,7-dioxa-8-aza-2-silatridecan-13-oate | C58H85N5O12Si2 | 详情 | 详情 |