Total Synthesis Of Autolytimycin And Its Analogs -Studieson Fragment Syntheses And Reductive Coupling Reaction

The new macrolactam of anticancer nature product discovered in recent years, autolytimycin and its analoges, which belong to the non-benzoquinone benzenid ansamycin, have the same effect as geladamycin in anticancer activity. But in the aspects of water-soluble, hepatotoxicity and resistance, they are superior to the current benzoquinone benzene ansamycin the clinical research used.Autolytimycin and its analoges are potential lead compounds and their total synthesis of are of great significance.The thesis concludes two parts. The first part is the syntheses of structure fragments of autolytimycin and its analoges. The second one is reseach on the method of developing aryl-alkyl reductive cross-coupling.Part one:Fragment synetheses1.Synthesis of aromatic ring fragment A2, A3, A4 aromatic ring fragments are synthesized from the 4-nitrophenol,and 4-bromo-phenol is synthesized from an aromatic ring fragment A6, aromatic ring fragment A7is synthesized from6-bromo-2-nitrophenol.5 aromatic ring fragments are synthesized.2.Synthesisof C9-15 ansa-ring fragment The brand new synthetic methods of C9-15 common fragments of the non-benzoquinone benzenoid ansamycin and autolytimycin from (R)-(+)-2,2-dimethyl-1,3-dioxolane-4-carboxaldehyde are developed. And the C9-15 analogs synthesis methods from L-glutamic acid are progressed.Part two:Studieson aryl-alkyl reductive couplingreactionMaking the reductive coupling reaction of m-Bromoacetanilide and 1-bromooctane as the model reaction, C15-C16 of aromatic ring fragment and ansa-ring fragmentconnection method is simulated. Ni(COD)2/2,2’-bipyridine (20%),the combination condition of reductive coupling method is screened out Which is mild and high yield.The above work laid the foundationfor the total syntheses of autolytimycin and its analoges.