VRC-3375

Chemical Name: 1-[2(R)-(N-Hydroxycarbamoylmethyl)hexanoyl]-L-proline tert-butyl ester
项目整合开发状态: Preclinical
项目研究机构: Vicuron Pharmaceuticals (Originator), Novartis (Codevelopment)
合成路线:The title compound has been prepared by solid phase synthesis.Attachment of (R)-2-butylsuccinic acid 1-fluorenylmethyl ester (I) to ArgoGel resin under Mitsunobu conditions affords the succinate-bound resin (II).Subsequent deprotection with piperidine in DMF leads to the acid-resin (III),which is further activated as the pentafluorophenyl ester (IV) upon treatment with pentafluorophenyl trifluoroacetate.Coupling of active ester (IV) with L-proline tert-butyl ester (V) furnishes amide (VI).Finally,cleavage of the resin by means of hydroxylamine in aqueous dioxane provides the target hydroxamic acid.

合成路线:In an alternative procedure,(R)-2-butylsuccinic acid 4-methyl ester (I) is coupled to L-proline tert-butyl ester (II) to afford amide (III).Then,displacement of the methyl ester group with hydroxylamine gives rise to the desired hydroxamic acid.