Study On The Synthesis And Biomedicine Of Norgestimate

As a new generation progesterone product, norgestimate is superior to the second-generation progesterone product levonorgestrel and the third-generation progesterone products-desogestrel and gestodene in terms of pharmacological, pharmacodynamic, toxicological and clinical aspects, as well as its safety and stability profiles. It is widely used as an oral contraceptive, acne therapy, and hormone replacement therapy for menopausal symptoms in women. At present, a significant amount of the products needs to be imported from foreign countries every year. In this paper, a process of di-esterification of levonorgesterol and hydrolysis of di-ester acids is adopted, and finally norgestimate is successfully synthesized, thus making a breakthrough on the foreign technical barrier in product commercialization. As compared with the synthetic methods reported in literature, the method not only has such advantages as reaction conditions mild, control easy, selectivity high and no secondary contamination, but also improves the recovery rate of norgestimate product at the same time.First, this paper investigates the optimal conditions for the reactions under actions and effects of multiple factors in microbial fermentation, cyclization and hydrogenation, lithium ammonium, wolf oxidation, alkyne hydrolysis, di-esterization, acid hydrolysis and oximization reactions; and solved the key technical issues in 17-hydroxy-acylation with stereoscopic barriers. The quality and recovery rate of the product are both greatly improved. On this basis is established the most effective synthetic method for norgestimate.The substances prepared in this paper such as Levonorgestrel, key intermediates and final product, after purity qualification with HPLC, was subjected to analyze by UV,IR,HNMR,CNMR and Mass. When analyzing concurrently with Ortho's Norgestimate specimen, the data obtained from analytical sample is identical to authentic, so thus the chemical structure and the quality of tittle compound are proved concretly.On the basis of norgestimate synthesis, the bio-medical characteristics of norgestimate are preliminarily studied in this paper. The findings in the paper have important theoretical and practical significance for the industrialization designs.