Development Of A Highly Efficient Synthesis Method For A Novel Anti-inflammatory Drug Active Ingredient (Z)-1,5-disubstituted-3-en-1-pentyne

Transition metal catalyzed coupling reaction of grignard reagent is one of the effective method to construct new carbon-carbon bonds. The kind of this reaction have raw materials and easy reagents, good stereoselectivity, Because of the reaction generates new carbon-carbon bonds and carbon-metallic bonding, is widely used in pharmaceuticals in organic synthesis. Along with the further research, how to control the carbon-carbon unsaturated bond metallization regioselectivity and stereoselectivity, caused the extensive attention of chemists.1,5-Diphenylpent-3-en-1-ynes is a kind of bioactive compound with strong anti-inflammatory activities separated from Lawsonia inermis which widely exists in natural products and has a certain biological activity. Therefore, this kind of compounds have wide application prospect and important application value in the pharmaceutical synthesis. Based on metal catalyzed coupling reaction of grignard reagent strategy, this research developed a kind of copper catalyst with grignard reagent reaction of 1,5-Diphenylpent-3-en-1-ynes method and a further exploration carried on as well. The main contents of the research were divided as following two parts:1. Propargyl compounds as one of the most important pharmaceutical intermediates is widely existed in nature. These compounds get great research value in the organic synthesis due to good plasticity of the acetylene. Base on the merit of the compounds a series of replaced propargyl alcohol was designed and synthesized followed by series of replaced propargyl alcohol ester/ethers derivatives were obtained according to the screening of the hydroxyl protection. At the same time, it also provide the raw material for 1,5-Diphenylpent-3-en-1-ynes synthesis..2. This part we studied under cheap low toxicity of copper catalyst, accessible instead vinyl acetylene propyl alcohol ester/ethers derivatives with grignard reagent reaction, generate 1,5-Diphenylpent-3-en-1-ynes method, and the optimization, and makes a deep exploration of the method by a series of 1,5-Diphenylpent-3-en-l-ynes. This method has wide application range, which can be of aryl and alkyl substituents, heterocyclic base and so on, have achieved very good yield.This article for 1,5-Diphenylpent-3-en-1-ynes is established for the synthesis of a simple, general and efficient method, make it more suitable for large-scale popularization and application in the field of drug synthesis.2. In the next step, 1,5-Diphenylpent-3-en-1-ynes was synthesized by vinyl acetylene propyl alcohol ester/ethers derivatives with grignard reagent reaction in copper catalyst. Under the optimization of the method, varied of 1,5-Diphenylpent-3-en-1-ynes were achieved. This method can be widely expande in the later synthesis by exchanging the substituent group into aryl, alkyl and heterocyclic. Good yields were obtained.This article for 1,5-Diphenylpent-3-en-1-ynes is established for the synthesis of a simple, general and efficient method, make it more suitable for large-scale popularization and application in the field of pharmaceutical synthesis. The results show that a simple, general and efficient synthesis method for 1,5-Diphenylpent-3-en-1-ynes was developed By using the low toxicity of copper catalyst, with easy to replace vinyl acetylene propyl alcohol ester reaction with grignard reagent or ether derivatives.