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【结 构 式】 
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【分子编号】37827 【品名】(3S,4S,5S)-4-[[(benzyloxy)carbonyl]amino]-5-methyl-3-[(triisopropylsilyl)oxy]heptanoic acid 【CA登记号】 |
【 分 子 式 】C25H43NO5Si 【 分 子 量 】465.70566 【元素组成】C 64.48% H 9.31% N 3.01% O 17.18% Si 6.03% |
合成路线1
该中间体在本合成路线中的序号：(VII)Protection of D-alloisoleucine (I) with Cbz-succinimide afforded benzyl carbamate (II). Activation of the carboxyl group of (II) as the pentafluorophenyl ester (III), followed by condensation with the lithium enolate of methyl acetate, gave beta-ketoester (IV). Stereoselective reduction of (IV) with KBH4 produced alcohol (V) as the major diastereomer. The hydroxyl group of (V) was protected as the triisopropylsilyl ether (VI), and then hydrolysis of the ester group of (VI) yielded carboxylic acid (VII).
| 【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 |
|---|---|---|---|---|---|---|
| (I) | 32739 | L-2-Amino-3-methylpentanoic acid; L-isoleucine | 73-32-5 | C6H13NO2 | 详情 | 详情 |
| (II) | 23508 | (2S,3S)-2-[[(benzyloxy)carbonyl]amino]-3-methylpentanoic acid | 3160-59-6 | C14H19NO4 | 详情 | 详情 |
| (III) | 37824 | 2,3,4,5,6-pentafluorophenyl (2S,3S)-2-[[(benzyloxy)carbonyl]amino]-3-methylpentanoate | C20H18F5NO4 | 详情 | 详情 | |
| (IV) | 23510 | methyl (4S,5S)-4-[[(benzyloxy)carbonyl]amino]-5-methyl-3-oxoheptanoate | C17H23NO5 | 详情 | 详情 | |
| (V) | 37825 | methyl (3S,4S,5S)-4-[[(benzyloxy)carbonyl]amino]-3-hydroxy-5-methylheptanoate | C17H25NO5 | 详情 | 详情 | |
| (VI) | 37826 | methyl (3S,4S,5S)-4-[[(benzyloxy)carbonyl]amino]-5-methyl-3-[(triisopropylsilyl)oxy]heptanoate | C26H45NO5Si | 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 |
合成路线2
该中间体在本合成路线中的序号：(VII)(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 |