Synthesis And Application Of 19-Hydroxyprogesterone

Progesterone,also known as progesterone,is the main hormone with biological activity secreted by the ovary.Therefore,the accurate determination of progesterone content in the body is of great significance for human health and the accurate treatment of diseases.The most commonly used method for detecting progesterone content is enzyme-linked immunosorbent assay(ELISA),which uses progesterone analogues to compete with progesterone to detect progesterone content.Therefore,the selection of compounds most similar to the spatial conformation of progesterone can provide more specific competitive antibodies,and the determination of progesterone content is more accurate.In the study of progesterone derivatives,the research group found that the 19-hydroxyprogesterone was closer to the spatial conformation of progesterone than the 11a-hydroxyprogesterone used in the current ELISA,which should be more conducive to the detection of progesterone content.However,the existing methods for the synthesis of 19-hydroxyprogesterone have some shortcomings,such as long reaction time,expensive parts,low yield and instability,and easy turnover of chiral center,etc.Therefore,it is of great significance to develop a method for the synthesis of 19-hydroxyprogesterone with high yield and low cost for the detection of progesterone content.This paper has completed the following research contents:By analyzing the existing processes,the key steps affecting the yield and the chiral center are determined and optimized.In the acetylation step of gestenolone 29,acetyl chloride was used to replace acetic anhydride,which not only greatly reduced the amount of raw material pyridine and acetic anhydride,but also greatly shortened the reaction time(from 60 hours to 0.5 hours).By exploring the reaction conditions,compound 32 was prepared by using cheap and readily available NBS instead ofexpensive n-bromide acetamide.Compound 35 was prepared by a clean and green catalytic oxidation method instead of chromium trioxide oxide compound 34.This method not only successfully carried out the oxidation and debromination in "one pot",but also avoided the turnover of c-17 chiral center in the original method,which improved the yield and simplified the operation.35 compounds in the process of the open loop,by optimizing the reaction system,to achieve the goal "one-step" ring opening preparation products 19-hydroxy progesterone,the original process not only shorten the step(two step),and yield of instability in the former step is the key problem,and on this basis,through the research process of open loop,puts forward the possible mechanism of open loop.Finally,19-hydroxyprogesterone was prepared from progesterone in six steps with a total yield of 37.96%,which was26.96% higher than that of the original process.This process laid a foundation for the preparation and development of 19-hydroxyprogesterone and its derivatives.Using 19-hydroxyprogesterone and butanedioic anhydride as starting mate-rials,19-hydroxyprogesterone succinate was prepared to detect progesterone antigen by succinate reaction with HRP,and the results of its competitive antibody with progesterone were preliminarily studied.it was found that the antigen based on19-hydroxyprogesterone mother nucleus could be used for progesterone detection.