Study On The Synthesis Of Phospholipid Monomer And Its Preparation Process Of Monolithic Chromatographic Column

In recent years,monolithic chromatography materials have played an increasingly important role in the field of drug analysis,detection,screening,research,and development.Monolithic chromatography columns（hereinafter referred to as monolithic columns）have the advantages of easy preparation,low back pressure,and high acid-base tolerance.Among them,the bio mimetic phospholipid membrane monolithic column was widely used to predict drug volume distribution,simulate drug membrane interaction,and enrich specific proteins because it can simulate the environment of cell membranes,so it has attracted much attention.However,only Regis Technologies,Inc in the US has commercialized phosphatidylcholine（Phosphatidyl Cholines,PC）columns on the market,and other phospholipid type columns such as glycerol phosphatidic acid（Phosphatidic Acid,PA）,which are closely related to physiology.It is still in the laboratory research stage.The reason is mainly limited by the limited variety of synthetic phospholipid monomers,the synthesis and preparation process were not mature enough,seriously affecting its commercialization process.In this paper,a new type of phospholipid monomer synthesis route was designed,including 1-12 alkyl-2-（12-methyl acrylamide xylene）-sn-glycerin-3-phosphate choline（1）-dodecanoyl-2-（12-methacryloyloxy dodecanoyl）-sn-glycero-3-phosphocholine,MDCPC),2-Methacryloyloxydodecycyl phosphate ethanolamine（2-Methacryloyloxydodecycyl phosphate ethanolamine,MDPE）,and further optimized the synthesis parameters of 2-Methacryloyl dodecyl phosphdic acid（2-Methacryloyl dodecyl phosphdic acid,MDPA）,simplifying the process and increasing the yield;Further exploration and optimization of the corresponding overall chromatography material preparation process.Those works will be helpful for the synthesis of similar phospholipid monolipids,and greatly promote the commercialization of phospholipid chromatography columns.In the first chapter,the source,physiological activity and classification of phospholipids as well as their application in pharmaceutical research were introduced,and the concept and application characteristics of phospholipid column were emphasized in this paper.The synthetic methods of phospholipid monomers in common use were reviewed,and the synthetic routes and problems were analyzed in detail.On this basis,the research purpose and significance of this paper were put forward.At the same time,the technical route of this research was proposed.In the second chapter,the synthetic route of phospholipids was analyzed in detail.On this basis,MDPA was synthesized and the effects of reaction temperature,reaction time,type of solvent and feed ratio on the yield were investigated.Referring to the relevant literature,the synthesis routes of MDPE and MDCPC were designed,and MDPE and MDCPC were synthesized,and the conditions of the new route were optimized from the factors such as reaction temperature,reaction time,feed ratio and so on.Compared with the previous route,the new route has the advantages of cheap and available raw materials,convenient operation and higher yield,which is of reference value for the industrialization guidance of related phospholipid monomers in the future.The structures of all compounds were confirmed by ¹H-NMR,¹³C-NMR and Ms.In the third chapter,the preparation conditions of phospholipid chromatographic column were optimized,and Poly（MDPA-co-EDMA）monolithic column was prepared by thermal initiation and photoinitiation.The proportion of phospholipid monomer and cross-linking agent was optimized to explore the optimal conditions so as to provide guidance for the industrialization of related phospholipid chromatographic columns.At the same time,it was applied to the separation of dimethyl phthalate,anisole,naphthalene and thiourea in sodium upgrade liquid phase,and its practicability was proved.The fourth chapter summarize the work progress and innovation of the full text and proposes improvements to the shortcomings of this article,hoping to provide a basis for the industrialization of phospholipid monomers and the commercialization of phospholipid chromatography columns in the future.