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【结 构 式】 
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【分子编号】47893 【品名】(8S,11S)-11-amino-8-isopropyl-2-oxa-6,9-diazabicyclo[11.2.2]heptadeca-1(15),13,16-triene-7,10-dione 【CA登记号】 |
【 分 子 式 】C17H25N3O3 【 分 子 量 】319.40392 【元素组成】C 63.93% H 7.89% N 13.16% O 15.03% |
合成路线1
该中间体在本合成路线中的序号：(VIII)Coupling on N-Boc-L-valine (I) with 3-bromopropylamine (II) by means of HBTU afforded amide (III). After Boc group cleavage in (III) using trifluoroacetic acid, the resultant amine (IV) was coupled with N-Boc-L-tyrosine (V) to yield the dipeptide amide (VI). Intramolecular cyclization of (VI) to produce the macrocycle (VII) was achieved by treatment with cesium carbonate in the presence of tetrabutylammonium iodide. Subsequent acid cleavage of the Boc protecting group of (VII) furnished the intermediate amine (VIII).
| 【1】 Mak, C.C.; Le, V.-D.; Wong, C.-H.; Elder, J.H.; Lin, Y.-C.; Design, synthesis, and biological evaluation of HIV/FIV protease inhibitors incorporating a conformationally constrained macrocycle with a small P3' residue. Bioorg Med Chem Lett 2001, 11, 2, 219. |
| 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) | 19733 | (2S)-2-[(tert-butoxycarbonyl)amino]-3-methylbutyric acid | C10H19NO4 | 详情 | 详情 | |
| (II) | 25449 | 3-bromo-1-propanamine; 3-bromopropylamine | 18370-81-5 | C3H8BrN | 详情 | 详情 |
| (III) | 47889 | tert-butyl (1S)-1-[[(3-bromopropyl)amino]carbonyl]-2-methylpropylcarbamate | C13H25BrN2O3 | 详情 | 详情 | |
| (IV) | 47890 | (2S)-2-amino-N-(3-bromopropyl)-3-methylbutanamide | C8H17BrN2O | 详情 | 详情 | |
| (V) | 25395 | (2S)-2-[(tert-butoxycarbonyl)amino]-3-(4-hydroxyphenyl)propionic acid | 3978-80-1 | C14H19NO5 | 详情 | 详情 |
| (VI) | 47891 | tert-butyl (1S)-2-[((1S)-1-[[(3-bromopropyl)amino]carbonyl]-2-methylpropyl)amino]-1-(4-hydroxybenzyl)-2-oxoethylcarbamate | C22H34BrN3O5 | 详情 | 详情 | |
| (VII) | 47892 | tert-butyl (8S,11S)-8-isopropyl-7,10-dioxo-2-oxa-6,9-diazabicyclo[11.2.2]heptadeca-1(15),13,16-trien-11-ylcarbamate | C22H33N3O5 | 详情 | 详情 | |
| (VIII) | 47893 | (8S,11S)-11-amino-8-isopropyl-2-oxa-6,9-diazabicyclo[11.2.2]heptadeca-1(15),13,16-triene-7,10-dione | C17H25N3O3 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XIV)The known N-Boc-hydroxyester (IX) was deprotected with trifluoroacetic acid to give (X). This was then coupled with the N-acetyl dipeptide (XI) to yield (XII), which was hydrolyzed by means of LiOH to provide carboxylic acid (XIII). The title compound was then obtained by HBTU-mediated coupling of acid (XIII) with the intermediate amine (VIII).
| 【1】 Mak, C.C.; Le, V.-D.; Wong, C.-H.; Elder, J.H.; Lin, Y.-C.; Design, synthesis, and biological evaluation of HIV/FIV protease inhibitors incorporating a conformationally constrained macrocycle with a small P3' residue. Bioorg Med Chem Lett 2001, 11, 2, 219. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IX) | 47894 | methyl (2R,3S)-3-[(tert-butoxycarbonyl)amino]-2-hydroxy-4-phenylbutanoate | C16H23NO5 | 详情 | 详情 | |
| (X) | 47895 | methyl (2R,3S)-3-amino-2-hydroxy-4-phenylbutanoate | C11H15NO3 | 详情 | 详情 | |
| (XI) | 47896 | (2S)-2-[[(2S)-2-(acetamido)-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylbutyric acid | C16H22N2O5 | 详情 | 详情 | |
| (XII) | 47897 | methyl (2R,3S)-3-[((2S)-2-[[(2S)-2-(acetamido)-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylbutanoyl)amino]-2-hydroxy-4-phenylbutanoate | C27H35N3O7 | 详情 | 详情 | |
| (XIII) | 47898 | (2R,3S)-3-[((2S)-2-[[(2S)-2-(acetamido)-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylbutanoyl)amino]-2-hydroxy-4-phenylbutyric acid | C26H33N3O7 | 详情 | 详情 | |
| (XIV) | 47893 | (8S,11S)-11-amino-8-isopropyl-2-oxa-6,9-diazabicyclo[11.2.2]heptadeca-1(15),13,16-triene-7,10-dione | C17H25N3O3 | 详情 | 详情 |