Asymmetrical Synthesis Of Alkaloid: (+)-Preussin And Mediceine Molecule: (-)-Nemonapride

The research for nature product chemistry makes prominent contribution to human health and medical treatment. So far, more than one third of drugs clinical applied are originated from nature products with bioactivity, isolated from body of animals and plants. But the content of bioactive molecular, mainly secondary metabolic, is limited in living organisms, which restrained the research of both theory and applications. Thus, total synthesis of nature products promotes largely on the solution of these problems, such as determination of structure, SAR research and related application. Alkaloids are alkaline compounds with a number of bioactivities contained in organism and they contain negative oxidation state nitrogen atoms. The organism used amino acids to synthesize alkaloids in issue, and the optic pure amino acids are easily obtained. Therefore, it is feasible and economical to asymmetrically synthesize alkaloids from natural amino acids whose chiral centres are retained.(+)-Preussin is an alkaloid with antifungal and antitumor activity. The thesis is based on the stereoselectively construction of 3,4-trans substituted 2-pyrrolidinone with the discovered compound 2-151, through oxidation and cyclization under the condition of RuCl₃-xH₂O/NaIO₄. Specifically, the optic pure (+)-preussin was synthesized from Boc-protected L-phenylalanine with 7 steps, yielded 27%.(-)-nemonapride is also an alkaloid drug with wide developmental prospects for it is an inhibitor of dopamine receptor. This thesis is also on the basis of the stereoselectively construction of 3,4-trans substituted 2-pyrrolidinone, describes the synthesis of (-)-nemonapride from Boc-protected L-alanine in 11steps with overall yield of 9%.