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【结 构 式】 
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【分子编号】43784 【品名】diisopropyl (2S,3R)-2-hydroxy-3-(2-methyl-2-propenyl)butanedioate 【CA登记号】 |
【 分 子 式 】C14H24O5 【 分 子 量 】272.34156 【元素组成】C 61.74% H 8.88% O 29.37% |
合成路线1
该中间体在本合成路线中的序号：(III)Treatment of butanedioate derivative (I) with methallyl iodide (II) and LDA in THF affords alkene (III), which is then reduced by hydrogenation over Pd/C and subjected to saponification by means of KOH in dioxane to yield succinic acid (IV). Protection of (IV) with 2,2-dimethoxypropane (V) and p-TsOH in DMF provides derivative (VI), which is then coupled with pentafluorophenol (VII) by using EDC in CH2Cl2 to furnish activated ester (VIII). Displacement of the pentafluorophenol moiety of (VIII) by treatment with L-tert-leucine methylamide (IX) in DMF gives methylamide derivative (X), which is deprotected with THF and HCl and condensed with O-benzylhydroxylamine (XI) by means of EDC to afford derivative (XII). Finally, (XII) is debenzylated by hydrogenation over Pd/C in EtOH to give the target compound.
| 【1】 Davenport, R.J.; Watson, R.J.; An improved synthesis of the broad spectrum matrix metalloprotease inhibitor marimastat. Tetrahedron Lett 2000, 41, 41, 7983. |
| 【2】 Dickens, J.P.; Crimmin, M.J.; Beckett, R.P. (British Biotech plc); Natural amino acid derivs. as metalloproteinase inhibitors. EP 0651738; EP 0651739; GB 2268933; GB 2268934; JP 1995509460; JP 1998204081; WO 9402446; WO 9402447 . |
| 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) | 43782 | diisopropyl (2S)-2-hydroxybutanedioate | C10H18O5 | 详情 | 详情 | |
| (II) | 43783 | 3-iodo-2-methyl-1-propene | C4H7I | 详情 | 详情 | |
| (III) | 43784 | diisopropyl (2S,3R)-2-hydroxy-3-(2-methyl-2-propenyl)butanedioate | C14H24O5 | 详情 | 详情 | |
| (IV) | 43785 | (2S,3R)-2-hydroxy-3-isobutylbutanedioic acid | C8H14O5 | 详情 | 详情 | |
| (V) | 10722 | 1-Methoxy-1-methylethyl methyl ether; 2,2-Dimethoxypropane | 77-76-9 | C5H12O2 | 详情 | 详情 |
| (VI) | 43786 | (2R)-2-[(4S)-2,2-dimethyl-5-oxo-1,3-dioxolan-4-yl]-4-methylpentanoic acid | C11H18O5 | 详情 | 详情 | |
| (VII) | 22662 | 2,3,4,5,6-pentafluorophenol | 771-61-9 | C6HF5O | 详情 | 详情 |
| (VIII) | 43787 | 2,3,4,5,6-pentafluorophenyl (2R)-2-[(4S)-2,2-dimethyl-5-oxo-1,3-dioxolan-4-yl]-4-methylpentanoate | C17H17F5O5 | 详情 | 详情 | |
| (IX) | 18843 | (2S)-2-amino-N,3,3-trimethylbutanamide | 89226-12-0 | C7H16N2O | 详情 | 详情 |
| (X) | 43788 | (2R)-N-[(1S)-2,2-dimethyl-1-[(methylamino)carbonyl]propyl]-2-[(4S)-2,2-dimethyl-5-oxo-1,3-dioxolan-4-yl]-4-methylpentanamide | C18H32N2O5 | 详情 | 详情 | |
| (XI) | 14640 | O-benzylhydroxylamine; 1-[(aminooxy)methyl]benzene | 622-33-3 | C7H9NO | 详情 | 详情 |
| (XII) | 43789 | (2S,3R)-N(1)-(benzyloxy)-N(4)-[(1S)-2,2-dimethyl-1-[(methylamino)carbonyl]propyl]-2-hydroxy-3-isobutylbutanediamide | C22H35N3O5 | 详情 | 详情 |