Study Of Synthesize Quinazolinone N-glycosyl Derivatives

Carbohydrates are widely exist in nature products,no matter it is the cellulose,starch in plants or glycoproteins,glycolipids and glycoconjugates in animals.They have the potential to exhibit important biological activities.Due to the diversity and complexity of the carbohydrate structure,the synthesis and biological activities evaluation of carbohydrates has become research topic in chemical biology field.On the other hand,as a natural alkaloid,quinazolinones have been exhibit great bioactivity and medicinal value.Tryptanthrin,Luotonin A,Rutaecarpine and many medications compounds containe quinazolinone skeleton in their structure.In this thesis,bases on the review of the synthetic methods of 4(3H)-quinazolinone derivatives,molecular modification by glycosylation and their activities study,we design and synthesis a series of quinazolinone-N-glycosylation compounds that have potential bioactivity.Firstly,a series of 2-aryl-quinazolinone compounds was synthesized.Two approaches for constructing the N-glycosidic bond have been explored.By screening five kinds of glycosyl donors,a favourable method for construction of quinazolinone-N-glycosidic bond was found.By detailedly analyzing the represent structure of reaction product,quinazolinone-N-3 glycosylation was identificated.By optimizing the reaction condition,a series of quinazolinone-N-3-glycosyl derivatives were synthesized in high yields.the research results of structure-activity relationships revealed that among the carbohydrates,the high activity glycosyl iododes are unfavore for quinazolinone's glycosylation.However,glycosyl bromide is a very good glycoslation regeat for quinazolinone under mild conditions.With regard to quinazolinone,the electrondrawing group on 2-ary ring is favorable to the glycosylation and gave higher yields than that of electrondonating group.The substituent groups on quinazolinone mother ring have less electronic effects to glycosylation.At last,the protecting groups on the sugar ring were removed,and quinazolinone-N-3 glycosyl derivatives were obtained in quantitative yields.