Studies On The Svnthesis Of Palonosetron Hydrochloride

Palonosetron hydrochloride is a kind of efficient and selective 5-HT3 receptor antagonist,using for the prevention of acute and delayed nausea and vomiting associated with the initiation and repeated treatment of moderate and highly emetic chemotherapy(CT).Palonosetron hydrochloride is the only second-generation selective 5-HT3 receptor antagonist for late-onset CINV,having good inhibitory effect on acute and delayed postoperative nausea and vomiting and other adverse reactions.It has many advantages,such as long-term efficacy,less adverse reactions,significant efficacy and so on.The properties,clinical application and synthesis of palonosetron hydrochloride were reviewed,and a synthetic route of palonosetron hydrochloride was designed:(S)-1,2,3,4-tetrahydro-1-naphthoic acid was used as starting material,via acylation,condensation,reduction,cyclization and salt formation,the target product was obtained.The total yield was over 40%and the chiral purity was 99.5%.The purity of the product was increased to 99%by optimizing the extraction and purification operation of the reduction reaction.The yield of the final step was improved to 90%by optimizing the diluent of salt forming step and the process of recrystallization.The structures of each reaction intermediates and the final product were confirmed by 1HNMR and 13CNMR.A more reasonable synthetic route was obtained through the optimization of the synthesis process of palonosetron hydrochloride.This synthetic route has the advantages of high yield,simple operation,environment friendly and suitable for industrial production.The quality of product was in line with the requirements of API.