The Synthetic Research Of The Anti-mutiple Scerosis Drug Glatiramer Acetate

Multiple sclerosis(MS) is one kind of autoimmune diseases which is characterized by white matter demyelination disease of the central nervous system(CNS) and it is caused by the action of individual genetic susceptibility and environmental factors. Multiple sclerosis is the most common and main disease of the white matter demyelination diseases of the central nervous system. Globally, there are about30people who suffers multiple sclerosis in a population of100000. This kind of disease can seriously affect the normal life of patients and can even cause disability. It brings misfortune to many patients. Glatiramer acetate is one of the earliest drugs which can delay the progression of multiple sclerosis and are confirmed clinically. In the past more than ten years, the drug has been used clinically and its efficacy and tolerability have been confirmed by doctors and patients. Besides, glatiramer acetate has brought more than one billion dollars of income for Teva Pharmaceuticals every year recently. The synthetic methods have been described in some patents for now. By analyzing those patents, we can find out that the main difference between them is the protection method and deprotection method of amino acids. The protection and deprotection methods chosen by the synthetic methods of current patents lead to relative complex process of deprotection and purification. Besides, most of the methods haven’t consider the protection of the phenolic hydroxyl group of the L-tyrosine. But the phenolic hydroxyl group is a relatively unstable group. We have designed a new synthetic method of GA. In this method, we protect the ε-amino of L-lysine with carboxybenzyl, protect the γ-carboxyl of L-glutamic acid with benzyl, and protect the phenolic hydroxyl group of the L-tyrosine with benzyl. The we transform those three protected amino acids and L-alanine into N-carboxyanhydrides. Then the four kinds of N-carboxyanhydrides are put together and polymerization reactions occurs by the addition of initiator. Then the protection groups are removed by catalytic hydrogenation in one step. The new synthetic method have provided a way to remove the protective groups in one step and purify the product in one step of dialysis. Besides, the method have considered the protection of L-tyrosine.The molar ratio of the four amino acids in products is a very important factor that determine if the products are qualified. The essay has determined the molar ratio of four kinds of N-carboxyanhydrides with which we can achieve qualified products. Besides, we have optimized the dosage of triphosgene during the synthetic process of N-carboxyanhydrides.At last, refer to the pharmacopeia, we have proceeded the identification and examination of glatiramer acetate.