Improvement On The Synthestic Process Of Neonicotinoid Insecticides Paichongding And Initial Synthesis Of Salinosporamide A

This thesis consists three parts:(1) Improvement on the synthestic process of neonicotinoid insecticides Paichongding; (2) Exploring asymmetric synthetic route towards Paichongding; (3) Initial synthesis study on the Salinosporamide A.Part I:As the excellent insect activity, broad insecticidal spectrum, low toxicity to mammals and aquatic animals, having a good system properties and the appropriate stability in the field, neonicotinoid insecticides has attracted intense interest. Li and his co-workers developed a new Paichongding which had a high activity to Nilaparvata lugens, Sulzer, Gennadius, etc. with a lower toxicity (>5000 mg/Kg). In the second chapter, we developed safe and effective, synthetic route based on the orginal process.1,3-Dibromo propane was used instead of expensive and highly toxic methyl iodide. At the same time, it generated 1,3-malonyl thiol being a higher boiling point by-product which could be recycled in order to improve the atom economy. This work also explored the crystallization conditions for the compound 6 so that the purification process of compound 6 was improved.Part II:Nearly 25% of commercial avaiable pesticides are molecules with chirality. The racemic pesticides will not only reduce the efficacy, the quality of agricultural products as well as polluting the environment, but also may cause injury or drug resistance because of the contained inefficient or ineffective enantiomer. Paichongding has two chiral centers. Therefore, the asymmetric organocatalyzed Michael addition of nitromethane to a,β-unsaturated aldehydes was used to construct the correct chiral center leading to the high expectations of synthetic chemical Paichongding. We designed two syntestic routes. One used L-proline to catalyze the reaction. The product was separated by chiral HPLC and gained four isomers. The other was unable to give the desired product as the final step of deprotection was failed.Part III:Proteasome inhibitor Salinosporamide A is one of the most promising drug candidates as potent treatment options in cancer therapy. Salinosporamide A entered phase I clinical trials for the treatment of multiple myeloma only three years after its discovery. This marine natural product contains a complex, densely functionalizedγ-lactam-(β-lactone pharmacophore, which is responsible for its irreversible binding to its target, theβsubunit of the 20S proteasome. The strong biological activity and the challenging structure of this compound have fueled intense academic and industrial research in recent years. The fourth chapter describes the synthesis of y-lactams. Firstly, Ag2O catalytic synthesis gave furo [3,2-b]-β/γ-lactam ring. Then, the ozone oxidation was applied to constructe theγ-Lactam ring with two correct chiral centers.