The Application Of Pictet-Spengler-type Cyclization Reactions In The Synthesis Of Pyridine [3,2-e] Pyrrolo [1,2-a] Pyrazines And Analogues

Pyridine-fused heterocyclic scaffolds show many biological activities. Several drugs containing sub-pyridine structure have been on the market. Quinolone is one typical example of pyridine-fused heterocyclic scaffolds. Many pyridine-fused heterocyclic scaffolds also exhibit biological activities.Pyrrole-fused pyrazine and its similar structures also have many many biological activities. The activities mainly focus on potent 5-HT receptor agonists and anti HIV virus. Basing on the summary, we find that the methods of synthesizing this kind of compounds are very limited. So it is very important to develop new methods to fulfill the needs. The aim of the dissertation was to design and synthesize Pyridine[3, 2-e]pyrrolo[1, 2-a]pyrazines and analogues via Pictet-Spengler-type cyclization reaction.Basing on the former research in our laboratory, an efficient method was developed for the construction of Pyridine[3, 2-e]pyrrolo[1, 2-a]pyrazines and analogues. 2-amino-3-nitro-6-chloro-pyridne was our starting material. It is commercially available, and very inexpensive. 2-(1H-pyrrole-1-yl)-3-amino-6-chloro -pyridine was prepared by two step process from the starting material. The first step was Clauson-Kass reaction, and the second step was reduction of nitro group. The cyclization reactions of 2-(1H-pyrrole-1-yl)-3-amino-6-chloro-pyridine with various aldehydes and ketons were conducted under the condition that trifluoroacetic acid and the acetonitrile refluxing. After that, we also study the reaction activity of 2-cholo, we can build chemical compounds library through that.In order to increasing the diversity of the compounds and saving money, we still use 2-amino-3-nitro-6-chloro-pyridne as our starting material. After reduction of nitro and Clauson-Kass reactions, we get the intermediate– pyridine 2-amino-3-(1H-pyrrol e-1-yl)- 6-chloro-pyridine. We still use the former method to cyclization. After the cyclization, we can still synthesize the similar compounds through 2-cholo.