Synthesis And Analysis Of Two Pharmaceutical Target Molecules

Synthesis and analysis of niclosamide to treat and control Schistosomiasis joponico. Niclosamide is also named atenase or yomesan commercially, and 5,2'-dichloro-4'-nitrosalicylanilide chemically. It can be used as both agrichemical and pharmaceutical with crude former and pure latter in general. According to synthesis and isolation of US patent, its purity cannot meet the requirement of pharmacopoeia. Here it is developed many modified methods for preparation and purification through selecting optimal dehydration agent, screening various solvent media, increasing reaction temperatures, optimizing preparation conditions even designing different synthesis pathways, and the expected results were not obtained, especially the final synthetic yield was not achieved at the desired level. A green chemical technique is utilized to solve the solubility problems of both m-chlorosalicylic acid and o-chloro-p-nitroaniline and to improve the synthetic yields at 83-85% level, equal to or more than 20% higher than 55-65% according to USP. In the refining the crude product by extraction and recrystalization , its purity is 94~96% and cannot meet the requirement of pharmacopoeia. Finally,good results were obtained with above 99% product purity by HPLC and more than 97% recovery through purification of the crude with some organic amines.Synthesis and analysis of both nedaplatin and oxaliplatin as the second- and third-era of cisplatins (CDDP). They are called cis-diamine glycolatoplatinum and 1R-trans-1,2-(N,N')-cyclohexanediamine-(2-)-O,O'-oxalicoplatinum. Two target compounds were synthesized from potassium chloroplatinium and the related materials through reduction, coordination and ligand exchange based on pathways fairly different from USPs and due to expensive even unavailable materials. Optimizations of synthetic pathways and reaction conditions are done both to enhance the yield by examining the reagent ratios and to avoid the foreign inorganic ions by using organic reducing agents. The final yields of total synthesis are located at 46% and 43% for nedaplatin by 5 steps and oxaliplatin by 4 steps, respectively. Structures of the synthesize molecules are both in perfect agreement with those of the reference standards by liquid chromatography and infrared spectroscopy.