Synthetic Studies Towards Daphniglaucin-type Daphniphyllum Alkaloid

This dissertation mainly focuses on the synthetic studies towards Daphniglaucin-type Daphniphyllum alkaloids and construction of the core skeleton of Daphnezomine-type Daphniphyllum alkaloids.We proposed a divergent route to synthesize Daphniglaucin-type and Daphnezomine-type Daphniphyllum alkaloids via an advanced common intermediate,which provides a feasible solution to prepare the Daphniphyllum alkaloids containing hydroxymethyl or methyl group at C-5.We firstly developed an efficient route to prepare the common intermediate,in which the 5/7 ring skeleton was constructed by[3+2]cycloaddition.Then the five membered ring with olefin was built via Dieckmann condensation reaction and SmI₂promoted radical reaction,and the advanced common intermediate was successfully achieved containing a lactone ring.Next,we explored the synthesis of Daphnezomine-type Daphniphyllum alkaloids.The quaternary carbon center was constructed through the methylation with iodine methane.The following ene-reaction failed to form the six membered ring.Using RCM reaction,the six membered ring was successfully constructed to give the 5/7/6tricyclic skeleton.This core structure has an opposite configuration at C-5 quaternary carbon center,based on X-ray diffraction,comparing with the natural product.Since then we had concentrated on the synthetic studies towards Daphniglaucin-type Daphniphyllum alkaloids.Begaining with successful building of quaternary center at C-5 via alkylation,the construction of 6/5 ring skeleton through[3+2]cycloaddition was failed.By being adjusted to stepwise strategy,the six membered ring was constructed via RCM reaction,followed by introduction of side chain containing nitrogen atom through Michael addition.Then the C-B-A-D tetracyclic skeleton containing an imine was achieved by reduction with SmI₂ and imidization in tandem.The reduction of the imine is in progress.