CEP-1612

Chemical Name: Nalpha-(2-Cyclopentyl-10-phthalimidodecanoyl)-Nomega-nitro-L-arginyl-L-leucinal
CAS No. 179538-06-8, 167416-10-6 (deleted CAS)
项目整合开发状态: Preclinical
项目研究机构: Cephalon (Originator)
合成路线:-(Benzyloxycarbonyl)-L-leucine (I) was activated as the mixed anhydride with isobutyl chloroformate and then coupled with N,O-dimethylhydroxylamine to produce the N-methoxyamide (II).Reduction of (II) with LiAlH4 at -78 C furnished aldehyde (III),which was converted to the corresponding diethyl acetal (IV) upon treatment with triethyl orthoformate.Subsequent hydrogenolytic removal of the benzyloxycarbonyl group of (IV) afforded leucinal diethylacetal (V).Coupling of N-Fmoc-nitroarginine (VI) with aminoacetal (V) via activation as the mixed anhydride with isobutyl chloroformate provided the protected dipeptide aldehyde (VII).The Fmoc protecting group of (VII) was then cleaved by using diethylamine in DMF-EtOAc to provide the intermediate (VIII).

合成路线:After conversion of cyclopentylacetic acid (IX) to the corresponding benzyl ester (X),alkylation with 1,8-diiodooctane in the presence of LDA generated the iodo ester (XI).Iodide displacement in (XI) with potassium phthalimide (XII) in hot DMF produced the substituted phthalimide (XIII).Then,hydrogenolysis of the benzyl ester group of (XIII) furnished carboxylic acid (XIV).Acylation of the intermediate dipeptide (VIII) with acid (XIV) by using BOP and HOBt yielded amide (XV).Finally,acid hydrolysis of the diethyl acetal function of (XV) gave rise to the title aldehyde.