Synthesis And Quality Control Research Of ATPR

At present, retinoids have found clinical utility in the treatment of skin disease and cancer. But it has also been suffered from two main disadvantages: chemoresistance to the drugs can occur easily, and can lead severe toxic side effects. The target compound 4-amino-2- trifluoromethyl - phenyl retinate(ATPR) was prepared using all-trans retinoic acid(ATRA) and trifluomethylphenyl derivative as the starting materials by condensation with DCC and DMAP , conveniently. Pharmacological studies have shown that ATPR could induce differentiation of NB4 leukemia cell and inhibit the proliferation of K562 leukemia cells and have a definite mechanisms of ATPR.Objective: Herein, we synthesized ATPR and identified it. Subsequently, we developed a HPLC method for the quality control of ATPR.Methods:1 The target compound 4-amino-2- trifluoromethyl - phenyl retinate(ATPR) was prepared using all-trans retinoic acid(ATRA) and trifluomethylphenyl derivative as the starting materials by condensation with DCC and DMAP , conveniently. Then, we purified crude ATPR by 70% ethanol .2 We identified ATPR by NMR, IR, HR-MS, Element Analysis, DSC, TGA and XRD method.3 We developed a HPLC method for the quality control of ATPR. The separation was performed on a Hypersil ODS 2 column (250mm×4.6mm,5μm). The mobile phase consisted of methanol-water (92:8).The UV detection was set at 367 nm. Result:1 Reaction yield of ATPR is from 28.6% to 56.71%. After purified by 70% Ethanol, we got content of 99.71%(by HPLC) of the refined ATPR.2 Structure of ATPR is confirmed by applying of NMR, IR, HR-MS Analysis, TGA, DSC method.3 ATPR was completely separated from impurities. The calibrated linear curve of ATPR concentration was with in 0.5~20μg·mL-1with the correlation coefficient of 0.9999.Conclusion: The reaction steps of synthesis of ATPR are simple, the reaction yeild is improved and the purity of ATPR is good. These efforts lay the foundation for industrial production of ATPR .This accurate and reliable HPLC method is applicable for the quality control of ATPR and its related substances.