Studies On The Synthesis Of Hypodematine And Its Derivatives

Hypodematine, a novel alkaloid, was isolated from the whole plant of a fern, Hypodematium sinense Iwatsuki. Its structure has been elucidated to have a novel skeleton of benzazocine with a phenyl substituent in 2-position. In this paper, we have finished the total synthesis of Hypodematine and its derivatives and revised its structure.The main work:1. We synthesized the hypodematine through the method of Beckmann rearrangement of benzoxyclohepten-5-one oxime mesylates that with Grignard reagents. From m-methoxy benzaldehyde to hypodematine, the synthesis was carred out in 9 steps efficiency. The total yield of the 9-step reactions was 47%.2. The mesylate was used as a eliminated group in the process of indenone synthesis.some indenone mesylates were also synthesized by the same method.3. Indenone oxime mesylates were synthesized and their rearrangement with grignard were studied.6 unrearrangement products were synthesized.4. The Beckmannrearrangement of thiophen mesylates under Grignard Reagent was also studied. The products of unrearrangement and ring-open were found.5. Some compounds of seven-ring imine were synthesized and their NMR data were compared with azocines.6. The stability of mesylates was studied, this found can give great help for the mechanism of rearrangement by Dr. Ma.7. The Beckmannrearrangement of naphthyl mesylate under Grignard Reagent was also studied. Both aryl Grignard Reagents and aliphatic Grignard Reagents were used as amphoteric reagents and react with naphthyl mesylate. The reaction of aliphatic Grignard Reagents and naphthyl mesylate give the unrearrangement products and that of aryl Grignard Reagents give both unrearrangement and rearrangement products. The reaction was shown by us that both mesylate and GR are important samely.8. The bioactivity of some synthetic compounds was tested, the mesylates of indenone oxime have some anticancer activity. All the compounds can not give the activity for nerve protection.160 compounds were synthesized in this dissertation, in which 76 compounds were the new ones with no report before. All the new compounds which relate with rearrangement were determined by NMR and HRMS.