Study On The Synthesis Of Toyocamycin Analogues

As the drugs for curing cancer,viruses and parasites,and fungi and bacteria infection,the synthesis and biological evaluation of nucleosides and nucleotide analogues have been developed half a century.Up to day,more than 30 nucleosides and their analogues have been approved for clinical,and others are also being tested at preclinical and clinical trials.Toyocamycin was showed strong biological activity for some tumor cells,viruses and bacteria.Therefore,the synthesis of its analogues also has been drawn people's widespread attention.In this paper,the nucleobase,introduced into the larger steric hindrance and electron-withdrawing functional group,was synthesized N~9 nucleoside compounds with the regioselectivity by using Vorbrüggen glycosylation reaction.And following hydrogenation reaction and ammonolysis reaction,a total of 10 terminal target products about 5'-deoxytoyocamycin,beta 2'-methyl beta-D-toyocamycin,beta L–toyocamycin,3'-deotoyocamycin analogues and their respective derivatives were obtained.Meanwhile,some crystalline structure of the intermediates and final products were unambiguously confirmed by X-ray diffraction analysis.In the process of ammonium hydroxide deprotecting functional groups of nucleoside compound,the explaination of the cyano that was attacked by nucleophile may be the stimulative factor because of the crystal structures of compound intermediates.In addition,through the systematic study of toyocamycin analogues,a feasible method for the synthesis of toyocamycin analogues was obtained,which is of great significance for the amplification of nucleoside libraries and the screening of antitumor,antiviral and antibacterial drugs.