Synthesis Of 3-Aryl-2-quinolinone And Transformation Of Cysteine

3-Aryl-2-quinolinones possess various bioactivities such as inhibitory effect of tumor cell migration and antiosteoporosis. They are precursors of a new class of nonpeptide gonadotropin releasing hormone receptor antagonists. However, the present synthetic routes for 3-aryl-2-quinolinones are suitable only for limited substrates. To study the structure-activity relationship and mechnism and to improve the solubility of 3-aryl-2-quinolinones, the detailed process and structure requirements for the isomerization of E-3-(2-aminophenyl)-2-phenylacrylic acids (E-A) to its Z-forms (Z-A), the intramolecular amidation of Z-A to 3-phenyl-2-quinolinones and the derivatization of the resulted products were investigated. The following results were obtained:1. Time-lapse ¹H NMR experiment indicated that E-A could be isomerized to Z-A under sunlight. E-A were easy converted to 3-phenyl-2-quinolinones by intramolecular amidation in protic and polar aprotic solvents but difficult in nonpolar aprotic solvents.2. Twenty-eight 3-phenyl-2-quinolinones were synthesized via E-A with high total yields, suggesting sunlight-induced isomerization of E-A followed by spontaneously intramolecular amidation is an efficient procedure for the syntheses of various 3-aryl-2-quinolinones.3. Three 3,4-diphenyl-2-quinolinones were synthesized by intramolecular annulation of 2-(N-phenylacetylamino)-benzophenone. It was observed that 2-nitrobenzophenone could be efficiently transformed to 3-aryl-2,1-benzisoxazole with EtONa in EtOH under reflux.4. Five derivatives of 3-phenyl-2-quinolinones containing carboxymethyl group and two derivatives containing amino acid were prepared for the first time. The lipophilic property of derivatives containing carboxymethyl group are improved. 5. Efficient preparation of dehydroalanine andβ-haloalanine derivatives were achieved by treating N-protected cysteine ester in PPh₃/LiOH/DMF and in PPh₃/NBS or NCS/CH₂Cl₂, respectively.