新产品编号:1141131

Chemical Name: 3-(4-Methoxyphenylsulfonyl)-7-phenylheptanohydroxamic acid
项目整合开发状态: Biological Testing
项目研究机构: Aventis Pharma (Originator)
合成路线:Horner-Emmons condensation of 5-phenylpentanal (I) with phosphonate (II) in the presence of NaH yielded tert-butyl 7-phenyl-2-heptenoate (III).Subsequent Michael addition of 4-methoxythiophenol (IV) to (III) using a catalytic amount of BuLi provided thioether (V).After acid deprotection of the tert-butyl ester of (V) with TFA,the resulting carboxylic acid (VI) was converted to acid chloride (VII) and then condensed with O-(trimethylsilyl)hydroxylamine to produce hydroxamic acid (VIII).Finally,sulfide oxidation of (VIII) with Oxone furnished the target beta-sulfonylhydroxamic acid.Alternatively tet-butyl ester (III) can be hydrolyzed first to the free acid (IX) with TFA,and then condensed with thiophenol (IV) by means of piperidine to afford the previously described carboxylic acid (VI).

合成路线:Hydroxyacid (III) was prepared by condensation of 5-phenylpentanal (I) with the dilithium anion of propionic acid (II).Cyclization of (III) upon treatment with dipyridyl disulfide and PPh3,and then with mercuric mesylate yielded an equimolar mixture of beta-lactones (IV) and (V),from which the desired cis isomer (IV) was isolated by flash chromatography.Subsequent ring opening of (IV) with the sodium salt of 4-methoxythiophenol (VI) provided carboxylic acid (VII).This was converted to acid the corresponding chloride by means of oxalyl chloride and then condensed with O-(trimethylsilyl)hydroxylamine to produce hydroxamic acid (VIII).Finally,sulfide oxidation of (VIII) with Oxone furnished the target sulfonylhydroxamic acid.