Asymmetric Synthesis Of Oxazolone And Thiazolone Derivatives With Pharmaceutical Potency

One of the fundamental objects of organic and medicinal chemistry has been the design, synthesis and preparation of molecules owning value as human therapeutic drugs. During the past decades, the increasing comprehension of drug interaction on a molecular level has led to the extending awareness of the importance of chirality in many medicinal products. The number of the non-racemic pharmaceuticals on the market was consistently increasing. With the proven utility in biological chemistry, oxazolone and thiazolone which belong to the heterocyclic compounds have received special attention gradually. According to the literature, these scaffolds associated with several biological active compounds and natural molecules, exhibiting such as antibiotic, antiviral, anti-tumor and anticonvulsant properties.Due to the operational and economic advantages, asymmetric organocatalysis has been proven to be a powerful tool for the synthesis of optically pure compounds. Therefore, we developed some efficient organocatalytic enantioselective addition systems for the preparation of unnatural amino acids which were used in the therapeutic peptides by using a readily prepared catalyst. In addition, a series of chiral thiazolone derivatives with well anti-cancer potency were synthesized from thiazolone module. By investigated and optimized the structure-activity relationship of these analogues, some of them have been developed as anti-cancer leading compounds. This dissertation includes five sections:In the first part, the recent progress of organocatalysis strategies for the asymmetric construction of oxazolone and thiazolone derivatives has been summarized.In the second section, an organocatalytic enantioselective addition of oxazolones and iV-tosyl aldimines has been developed. The process is promoted by a readily prepared cinchona alkaloid ligand and affords a series of chiral a-disubstituted α,β-diamino acid derivatives. These unnatural amino acids could be used in therapeutic peptides synthesis.In the third part, we synthesized a series of chiral 2-(ethylthio)-thiazolone derivatives via a direct, enantioselective aza-Mannich addition from N-tosyl aldimines and thiazolones. And these derivatives have been found to show well anticancer activities against five different cancer cell lines using the MTT assay.In the fourth part, on the basis of previous study, we presented a highly efficient strategy to obtain a series of chiral thiazolones derivatives via a Michael addition. Some of the analogues with well anti-cancer potency were developed as new anti-cancer leading compounds.The last part was the summary of each chapter in this dissertation.