Synthesis Of 5H-isochromeno[4,3-Blindolizin-5-one And Pyrido[3,2-B] Indolizine Compounds

N-containing heterocycles have always been an important research object in organic chemistry and pharmaceutical chemistry,which are extremely rich and widely exist in nature.A lots of natural products and synthetic drugs N-containing heterocycles.And indolizines are an important member of N-containing heterocycles.Many natural products or synthetic compounds containing indolizine structure,such as camptothecin,swainsonine,chestnut spermine and so on.They have many important pharmacological effects,including anti-cancer,anti-inflammatory and other activities.At present,there are many methods to synthesize indolizine compounds,but many of them have some defects,such as expensive metal reagents or harsh reaction conditions.In Chapter 1 of this paper,indolizines and isocoumarins were reviewed,and green chemistry was introduced.In Chapter 2,a green and simple method was established to synthesize a novel kind of 5H-isochromeno[4,3-b]indolizin-5-ones.The green solvent PEG（200）was used as the reaction medium to synthesize 5H-isochromeno[4,3-b]indolizin-5-ones compound 3 in one pot with the available ninhydrin monohydrate 1 and some 2-pyridine acetic derivatives 2.Moreover,the post-treatment of the reaction was very simple,and the product could be obtained by simple filtration and washing.This method pioneered the formation of isocoumarin structure while constructing indolizine structure.At present,there is no drug containing indolizine and isocoumarin structure at the same time.We carried out preliminary anticancer activity test on the product and found that compound 3r has obvious anticancer activity on lung cancer H1299 and liver cancer MHCC97H cells.In Chapter 3,a cheap metal Mn（Ⅲ）was used as a single electron oxidant to oxidize 2-pyridine acetic derivatives 2 to synthesize pyrido[3,2-b]indolizine compound 4.Mn（Ⅲ）was first used to synthesize indolizine structure.Mn（Ⅲ）oxidizes the α-carbon of 2 to form a carbon radical to attack the double bond on the pyridine ring of another molecule 2.The aromaticity of pyridine ring was destroyed during the reaction,and finally the aromaticity of structure was restored through oxidation.