Efficient Synthesis Of Novel Indolizine C-nucleoside Analogues In One Pot

C-nucleoside and its analogues are important stable analogues of bionucleoside characterized by C-C glycosidic bond.Many carbonucleoside analogues have antimicrobial,antiviral and anti-tumor activities,and play an important role in chemical biology and pharmaceutical chemistry.The synthesis of novel C-nucleoside analogues is of great significance for the lead synthesis of antimicrobial,antiviral and antitumor drugs.Yin oxazine(also called indoles oxazine)is a kind of five and six yuan for nitrogen heterocyclic compounds,the structure exists widely in natural products and drugs,have fight leukemia,tuberculosis,antidepressant,antioxidant,PLA2 inhibitors,phosphatase inhibitor,aromatase inhibitors,15-lipoxygenase inhibitor,serotonin(5-HT3)receptor antagonist and biological activities such as histamine H3 receptor antagonists.In this paper,a variety of glycoacetylenes,pyridines and their substituents,a-bromocarbonyl compounds and their corresponding bases were synthesized by 1,3-dipole cycloaddition and other reactions in a one-pot method with a high yield of indazine C-nucleoside analogs.The method is convenient and efficient,and is suitable for various substrates with different structures.Firstly,D-glucose,D-ribose,D-fructose,D-galactose and D-mannose were used as the basic raw materials to prepare corresponding alkynylides through multi-step reactions.Selection of fructose acetylene and benzoyl chloride by introducing benzene formyl Sonogashira reaction,again with the lack of electronic sugar acetylene,pyridine,alpha bromine generation of phenyl ethyl ketone synthesized from corresponding fructose Yin oxazine C-nucleoside analogues,and with the reaction as a template,through to the reaction temperature,alkali type,optimizing the conditions of various solvents,found the best reaction condition,with high yield of target product.The structure of the target compound was characterized by IR,1H-NMR,13C-NMR,DEPT-135,1H-1H COSY,HSQC,HMBC and HRMS.Under optimal reaction conditions,pyridine and α-bromoacetophenone substrates were extended to their substitutes,respectively,to react with e-fructose deficient alkyne in three components to obtain fructose indazine C-nucleoside analogs with novel structures.On this basis,the sugar acetylene substrates by fructose acetylene extend to other 7 kinds of electron-deficient sugar acetylene(respectively by d-glucose,D-ribose,D-galactose and D-mannose preparation),make it respectively and pyridine,alpha bromine generation of acetophenone and replacing reaction,get on the diversity of shape and structure of a series of new type Yin oxazine class C-nucleoside analogues,and through IR,1H-NMR,13 C NMR,DEPT-135,1H-1H COSY,HSQC,HMBC and HRMS to the characterization of their structure.The possible mechanism of the reaction was speculated,and the regional selectivity of the 1,3-dipole addition reaction was explained by quantum calculation of the charge distribution of the tri-bond of glycoacetylene.