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【结 构 式】 
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【分子编号】37833 【品名】(1S)-2-methyl-1-[(2,3,4,5,6-pentafluorophenoxy)carbonyl]propyl (3S,4S,5S)-4-[[(benzyloxy)carbonyl]amino]-5-methyl-3-[(triisopropylsilyl)oxy]heptanoate 【CA登记号】 |
【 分 子 式 】C36H50F5NO7Si 【 分 子 量 】731.873056 【元素组成】C 59.08% H 6.89% F 12.98% N 1.91% O 15.3% Si 3.84% |
合成路线1
该中间体在本合成路线中的序号：(XIII)(S)-2-Hydroxyisovaleric acid (IX) was obtained from L-valine (VIII) by diazotization in the presence of sulfuric acid. After protection as the allyl ester (X), coupling with isostatine derivative (VII) using DCC and DMAP afforded (XI). Then, removal of the allyl group of (XI) by means of Pd(PPh3)4 gave acid (XIII), which was activated as the pentafluorophenyl ester (XIII).
| 【1】 Liang, B.; et al.; The first total synthesis of (-)-tamadarin A. Org Lett 1999, 1, 8, 1319. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 11463 | 3-Bromo-1-propene; 3-Bromopropene；allyl bromide | 106-95-6 | C3H5Br | 详情 | 详情 | |
| (VII) | 37827 | (3S,4S,5S)-4-[[(benzyloxy)carbonyl]amino]-5-methyl-3-[(triisopropylsilyl)oxy]heptanoic acid | C25H43NO5Si | 详情 | 详情 | |
| (VIII) | 37828 | L-2-Amino-3-methylbutyric acid; L-2-Aminoisovaleric acid; 2-Aminoisovaleric acid; L-2-Amino-3-methylbutyric acid; L-alpha-Aminoisovaleric acid; L-valine; (S)-(+)-Valine; (S)-alpha-Aminoisovaleric acid | 72-18-4 | C5H11NO2 | 详情 | 详情 |
| (IX) | 37829 | (2S)-2-hydroxy-3-methylbutyric acid | C5H10O3 | 详情 | 详情 | |
| (X) | 37830 | allyl (2S)-2-hydroxy-3-methylbutanoate | C8H14O3 | 详情 | 详情 | |
| (XI) | 37831 | (1S)-1-[(allyloxy)carbonyl]-2-methylpropyl (3S,4S,5S)-4-[[(benzyloxy)carbonyl]amino]-5-methyl-3-[(triisopropylsilyl)oxy]heptanoate | C33H55NO7Si | 详情 | 详情 | |
| (XII) | 37832 | (2S)-2-([(3S,4S,5S)-4-[[(benzyloxy)carbonyl]amino]-5-methyl-3-[(triisopropylsilyl)oxy]heptanoyl]oxy)-3-methylbutyric acid | C30H51NO7Si | 详情 | 详情 | |
| (XIII) | 37833 | (1S)-2-methyl-1-[(2,3,4,5,6-pentafluorophenoxy)carbonyl]propyl (3S,4S,5S)-4-[[(benzyloxy)carbonyl]amino]-5-methyl-3-[(triisopropylsilyl)oxy]heptanoate | C36H50F5NO7Si | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XIII)Hydrogenolysis of the Cbz group from the fully protected tetrapeptide (XIV) gave the free amine (XV). This was coupled with the activated ester (XIII) to provide the linear precursor (XVI). Selective cleavage of the silylethoxymethyl ester of (XVI) with MgBr2.Et2O, followed by hydrogenolysis of the Cbz group furnished (XVII). Subsequent macrocyclization of (XVII) using HATU afforded the cyclic depsipeptide (XVIII).
| 【1】 Liang, B.; et al.; The first total synthesis of (-)-tamadarin A. Org Lett 1999, 1, 8, 1319. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XIII) | 37833 | (1S)-2-methyl-1-[(2,3,4,5,6-pentafluorophenoxy)carbonyl]propyl (3S,4S,5S)-4-[[(benzyloxy)carbonyl]amino]-5-methyl-3-[(triisopropylsilyl)oxy]heptanoate | C36H50F5NO7Si | 详情 | 详情 | |
| (XIV) | 37834 | [2-(trimethylsilyl)ethoxy]methyl (2S,3R)-3-[[(2S)-2-[[[(2S)-1-((2S)-2-[[(benzyloxy)carbonyl]amino]-4-methylpentanoyl)pyrrolidinyl]carbonyl](methyl)amino]-3-(4-methoxyphenyl)propanoyl]oxy]-2-[(tert-butoxycarbonyl)amino]butanoate | C45H68N4O12Si | 详情 | 详情 | |
| (XV) | 37835 | [2-(trimethylsilyl)ethoxy]methyl (2S,3R)-3-[[(2S)-2-[([(2S)-1-[(2S)-2-amino-4-methylpentanoyl]pyrrolidinyl]carbonyl)(methyl)amino]-3-(4-methoxyphenyl)propanoyl]oxy]-2-[(tert-butoxycarbonyl)amino]butanoate | C37H62N4O10Si | 详情 | 详情 | |
| (XVI) | 37836 | C67H111N5O16Si2 | 详情 | 详情 | ||
| (XVII) | 37837 | C53H91N5O13Si | 详情 | 详情 | ||
| (XVIII) | 37838 | C53H89N5O12Si | 详情 | 详情 |