Design And Synthesis Of Polycyclic Benzothiazole Chiral Derivatives

Among many pharmaceutical intermediates and post-market drugs,heterocyclic compounds play an important role.Heterocyclic compounds containing benzothiazole skeleton have received widespread attention and are widely used in the field of medicinal chemical synthesis as synthetic templates and pharmacodynamic frameworks due to its varieties biological activities.In addition,with the rapid development of pharmaceutical,chiral drugs have become an important field and attracted the attention and research of scientists around the world.However,in the synthesis methods of chiral benzothiazole compounds that have been reported so far,most of them have problems such as harsh reaction conditions,poor stereoselectivity and universality,so it is still challenging to synthesize benzothiazole derivatives with good yields and enantioselectivity.Asymmetric catalytic synthesis is a common method used by scientists which is economical,practical,efficient and environmentally friendly.Chiral phase transfer catalyst as an efficient,cheap and readily available catalyst,is widely used in scientific research and industrial production.Therefore,we use an easy-to-synthesize benzoylbenzothiazole compound containing active methylene group,under the combined action of base and phase transfer catalyst,a series of chiral 2,3-dihydro-1H-benzo[4,5]thiazolo[3,2-a] pyridine skeletons were obtained by Michael addition and intramolecular asymmetric cyclization withα,β-unsaturated amide compounds.The method is simple to operate,the reaction condition is mild,green and environmentally friendly,and the corresponding products can be obtained with high yields(up to 99%)and high enantioselectivity(up to 99:1 er),furthermore,the method has good adaptability to different substrates.In addition,to demonstrate the practicality of this method,we further carried out a derivatization of the target compounds.