The Study Of Synthesis Of Paclitaxel Side Chain Based On [3+2] Cycloaddition

The discovery of Taxol has long been considered as a landmark event in the history of natural medicine,mainly for the treatment of ovarian cancer,breast cancer,non-small cell lung cancer and so on.Paclitaxel is present in yew which belongs to rare plants and the natural content is very low.By Separating and extracting from nature it can not meet the demand of the market for Taxol.The complex structure of Taxol makes it difficult for the synthesis.Currently,semi-synthetic route is a normal method,that is obtaining Taxol by connecting the side chain with the natural and more accessible 10-DAB.The Taxol side chain belongs to ?-amino-?-hydroxyl acid derivatives and there are many methods for synthesizing such compounds.The thesis includes two parts of research work.In the first part,the introduction of a new study on the method which our group has been published for the efficient synthesis of ?-amino-?-hydroxyl acid derivatives by Mannich addition reaction based on oxonium ylide as an intermediate was describled.In the second part,we mainly introduce the[3 + 2]cycloaddition reactions of EDA,aldehyde and N-Bz imines based on carbonyl ylide trapping reactions,which accomplished the synthesis of Taxol side chain and a variety of its analogues by one-pot method.In addition,the[3+2]cycloaddition of N-Bz imines and carbonyl ylide has not been reported,what's more,the[3+2]cycloaddition of carbonyl ylide generated from alkyl aldehyde has been rarely developed,thus the part of the work has a certain degree of novelty from a methodological point of view.