Studies On The Synthesis Of Amphiphilic Molecules With Quaternary Ammonium Salts Base On Bile Acid And Their Gel Properties

Bile acids are a class of natural steroidal compounds, which were widely used in clinical treatments as drugs. Bile acids have the distinctively curved and rigid steroidal skeleton which form their hydrophobic face, a few of hydroxyls and carboxy group which form hydrophilic face, so these compounds have natural amphilicities. Especailly, the proper chemical modifications were made in natural bile acids which can improve further the special surface properties. The modified bile acids should be used in exploiting medicines and new materials. Based on the results of the structure-activity relationship of our previous researches on the modified bile acids, in this paper, Synthesis of quaternary ammonium salt amphiphilic molecules based on acid and its gel properties. Three parts were divided in this thesis.Part one:Synthesis of C3 the quaternary ammonium salt of lithocholic acid:The commercially available lithocholic acid was used as the starting material, the C3 hydroxyl of lithocholic acid was oxidized to carbonyl by using the Jones reagent firstly. Next, the C17 carboxyl was protected by esterification. The following reductive animation of the C3 3-oxosteroid with piperidine, pyrrole, morpholine and aniline was carried out respectively. At last, the alkylation reaction of the obtained amine with methyl iodide gave six C3 quaternary ammonium salts of lithocholic acid. The products were characterized by’H NMR, 13H NMR, IR, and LC-MS. The single crystal structures of five intermediate amines were confirmed by X-ray diffraction method.Part two:Synthesis of the C17 quaternary ammonium salts of cholic acid:The commercially available cholic acid, chenodeoxycholic acid and a class of various primarily long-chain amines (C6-C18) used as starting materials, in the presence of N,N-dicyclohexyl carbodiimide (DCC) and 1-hydroxy benzotriazole (HOBt) as condensation agents, a series of amidosteroids (C6-C18) were synthesized firstly. Next the resultant amides were reduced by lithium aluminum hydride to yield the secondary amines. Finally, in the presence of potassium carbonate as a catalyst, the reaction of the obtained secondary amines with the excess methyl iodide gave twelve C17 quaternary ammonium salts of cholic acid. The products were characterized by 1H NMR,13H NMR, IR, and LC-MS.Part three:Studies on preparation and characters of gel:First, we tested the surface tension, critical micelle concentration (CMC) and the forming gel of the quaternary ammonium salts. The results showed the selected six quaternary ammonium salts can form the gel. We tested gel’s gel-sol phase transition temperature (Tg), minimum gelation concentration (MGC) and rheological properties. We analyzed the testing data. The shapes of dryed gel were observed under scanning electron microscope (SEM). Additionally, preliminary researches on the organogel of steroid amides also have been done.