Study On The Synthesis Of Alosetron Hydrochloride

Irritable bowel syndrome (IBS) is a common disease resulting from disorders of gastrointestinal digestive function. Clinically, it was characterized by abdominal discomfort, abdominal pain, diarrhea, constipation and other bowel abnormalities. At present, the exact pathogenesis of IBS is still unknown. This heterogeneous disease is characterized with individual specificity and multiple etiological factors. Treatment is directed primarily at relieving the symptoms. As the incidence of IBS rises continuously, more and more IBS patients suffer from the disease, and drug treatments of IBS have been paid close attention. Alosetron hydrochloride, the chemical name of which is 2,3,4,5-tetrahydro-5-methyl-2-[(5-methy1-1H-imidazole-4-yl)methyl]-1H-Pyrido[4,3-b]indol-l-onehydrochloride,was developed and made by GlaxoWellcome company. In 2000, alosetron hydrochloride became the first drug for treating IBS, which got approved by the United States Food and Drug Administration (FDA). Alosetron hydrochloride is a 5-HT3 receptor antagonist. As the limited drug, it mainly applies in the treatment of female patients with diarrhea-predominant irritable bowel syndrome (D-IBS).The research on the synthesis of alosetron hydrochloride has important realistic meaning and good prospects for development. Many kinds of synthetic methods for alosetron hydrochloride have been reported at home and abroad. This paper learned from synthetic routes which have been described, and improved them on the basis of relevant documents. Ultimately, the five-step method was determined as the synthetic route for alosetron hydrochloride. Alosetron hydrochloride was synthesized form 2,4-dioxoy-3-piperdine carboxylic acid, methylester, ion(1-),sodium by hydrolytic decarboxylation condensation with N-methyl-2-phenylhydrazine, then cyclization in sulfuric acid, and condensation with 4-hydroxymethyl-5-methyl imidazole hydrochloride, and salt formation with hydrochloric acid. After determining the synthetic route, the paper investigated the extraction conditions of each step from some factors, such as time, temperature, kind of solvent, order of feed, composition of feed and post-processing techniques, and made the every best condition clear. The yield of alosetron hydrochloride in the experimental condition was 31.7 percent.This method that was improved can meet the demands of a large scale production by making cost down, simplifying working processes, reducing pollution, and raising the yield of the product. Further, a large amount of raw materials had been consumed before the condition was determined, so the paper referred to relevant synthesis documents and studied the synthesis of 2,4-dioxoy-3-piperdine carboxylic acid, methylester, ion(1-),sodium. This method can not only supply raw materials for the preliminary studies, but also greatly reduce the cost of the research stage.Alosetron hydrochloride has been confinned by IR, UV-VIS,1HNMR,13CNMR,DEPT, 13C-1H COSY, MS.