Acivicin, U-42126, NSC-163501, ACIA, AT-125

阿西维辛Chemical Name: (alphaS,5S)-alpha-Amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid; (alphaS,5S)-alpha-Amino-3-chloro-2-isoxazoline-5-acetic acid
CAS No. 42228-92-2
项目整合开发状态: Phase III
项目研究机构: National Cancer Institute (Originator), Pfizer (Originator)
合成路线:A new procedure for the synthesis of acivicin has been reported:The photochlorination of L-glutamic acid (I) gives 3-chloroglutamic acid (II); the corresponding diastereomers were separed by ion-exchange chromatography over Dowex-50 (H+).The reaction of (II) with benzyl chloroformate (III) affords N-carbobenzoxy-3-chloroglutamic acid (IV),which is anhydrized with dicyclohexylcarbodiimide to the corresponding protected anhydride (V).The reaction of (V) with lithium N-hydroxyphthalimide (VI) yields the phthalimidoxy derivative (VII),which is converted to the protected hydroxamic acid (VIII) by a treatment with hydroxylamine.The cyclization of (VIII) with triethylamine affords N-carbobenzoxytricholomic acid (IX),which is esterified with diphenyldiazomethane (X) giving the corresponding protected benzhydryl ester (Xl).The reaction of (XI) with dichloro-trisdimethylaminophosphorane (XII) yields the deprotected final compound (XIII),which is finally treated with trifluoroacetic acid and thioanisole (A).