-Drug Synthesis Database

【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 合成路线2

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).

参考文献中间体

【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).

参考文献中间体

【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	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

Drug NewChemical Entity Original Patent(1)