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【结 构 式】

【药物名称】

【化学名称】N-Acetyl-L-tyrosyl-N1-[1(S)-benzyl-2(R)-hydroxy-3-[8(S)-isopropyl-7,10-dioxo-2-oxa-6,9-diazabicyclo[11.2.2]heptadeca-1(15),13,16-trien-11(S)-ylamino]-3-oxopropyl]-L-valinamide

【CA登记号】

【 分 子 式 】C43H56N6O9

【 分 子 量 】800.96057

【开发单位】Scripps Research Institute (Originator)

【药理作用】AIDS Medicines, Anti-HIV Agents, ANTIINFECTIVE THERAPY, HIV Protease Inhibitors

合成路线1

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

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
Extended Information