新产品编号:1316733

Chemical Name: 3(R)-[N-[1(S)-(1H-Indol-3-ylcarbonyl)-2-phenylethyl]carbamoyl]-5-methyl-2(S)-(4-pentenyl)hexanehydroxamic acid
项目整合开发状态: Biological Testing
项目研究机构: Abbott (Originator)
合成路线:Friedel Crafts acylation of indole (II) with tert-leucine N-carboxyanhydride (I) in the presence of AlCl3 gave aminoketone (III).Subsequent condensation of (III) with the succinate building block (IV) in DMF afforded succinamide (V).Further deprotection of the tert-butyl ester of (V) by treatment with trifluoroacetic acid provided carboxylic acid (VI),which was coupled with O-tert-butyldimethylsilyl hydroxylamine (VII) in the presence of EDC and HOBt to yield,after desilylation,the target hydroxamic acid.

合成路线:Friedel Crafts acylation of indole (II) with phenylalanine N-carboxyanhydride (I) in the presence of AlCl3 gave aminoketone (III).Subsequent condensation of (III) with the succinate building block (IV) in DMF afforded succinamide (V).Further deprotection of the tert-butyl ester of (V) by treatment with trifluoroacetic acid provided carboxylic acid (VI),which was coupled with O-tert-butyldimethylsilyl hydroxylamine (VII) in the presence of EDC and HOBt to yield,after desilylation,the target hydroxamic acid.

合成路线:Friedel Crafts acylation of indole (II) with phenylalanine N-carboxyanhydride (I) in the presence of AlCl3 gave aminoketone (III).Subsequent condensation of (III) with the succinate building block (IV) in DMF afforded succinamide (V).Further deprotection of the tert-butyl ester of (V) by treatment with trifluoroacetic acid provided carboxylic acid (VI),which was coupled with O-tert-butyldimethylsilyl hydroxylamine (VII) in the presence of EDC and HOBt to yield,after desilylation,the target hydroxamic acid.

合成路线:Friedel Crafts acylation of indole (II) with tert-leucine N-carboxyanhydride (I) in the presence of AlCl3 gave aminoketone (III).Subsequent condensation of (III) with the malate building block (IV) in DMF afforded amide (V).Further deprotection of the tert-butyl ester of (V) by treatment with trifluoroacetic acid provided carboxylic acid (VI),which was coupled with O-tert-butyldimethylsilyl hydroxylamine (VII) in the presence of EDC and HOBt to yield,after desilylation,the target hydroxamic acid.

合成路线:Condensation of N-(tert-butoxycarbonyl)phenylalanine (I) with phenyllithium furnished ketone (II).The N-Boc group of (II) was deprotected with HCl in dioxan to yield aminoketone (III),which was then condensed with the succinate building block (IV) in DMF to afford succinamide (V).Further deprotection of the tert-butyl ester of (V) by treatment with trifluoroacetic acid provided carboxylic acid (VI),which was coupled with O-tert-butyldimethylsilyl hydroxylamine (VII) in the presence of EDC and HOBt to yield,after desilylation,the target hydroxamic acid.

合成路线:Condensation of N-(tert-butoxycarbonyl)phenylalanine methyl ester (I) with pyrrolyl magnesium bromide (generated from pyrrole (II) and MeMgBr) furnished ketone (III).The N-Boc group of (III) was deprotected with HCl in dioxan to yield aminoketone (IV),which was then condensed with the succinate building block (V) in DMF to afford succinamide (VI).Further deprotection of the tert-butyl ester of (VI) by treatment with trifluoroacetic acid provided carboxylic acid (VII),which was coupled with O-tert-butyldimethylsilyl hydroxylamine (VIII) in the presence of EDC and HOBt to yield,after desilylation,the target hydroxamic acid.