Study On The Synthesis And Structure-activity Relationship Of Clarithromycin 4"-O-deoxydimethylamino Sugar Derivatives

The anti-resistant microlides have been widely investigated in recent years.In spite of ketolides,macrolide 4"-OH modified derivatives showed a potent against resistant pathogens.Desosamines were employed as new sugar substituents,which played an important role in bioactivity of macrolides.The 11,12-aromatic side chain was related to the extra interaction between macrolide molecule and its receptor.According to the statements above,we did the following work:1.Design,synthesis and antimicrobial activities of clarithromycin 4"-O-desosaminyl derivatives.To seek new binding,sites between macrolides and their ribosome receptors,and to study the SAR of such compounds,two 6-deoxy-desosainine donors were synthesized through 13 steps of reactions.Nine target compounds were yielded,and their activities were tested.The activities of these compounds were generally preserved against the sensitive pathogens,and compounds 31 and 33 showed better activities than carthromycin against 2 strains of MRSE.2.Design and synthesis of 11,12-aromatic clarithromycin 4"-O-desosaminyl derivatives.To get target compounds with better activity and further study the SAR,a series of 11,12-aromatic clarithromycin 4"-O-desosaminyl derivatives were designed and synthesized.Macrolide precursors with three different side chains were anchored with two desosamine donors,and after deprotection,six target compounds were yielded.Their antimicrobial activitied are being tested.71 compounds have been synthesized in all.Thereinto,31 macrolide dercatives have not been reported in literature yet.Their structure have been confirmed by 1HNMR,13CNMR,HR MS.