Reseaches On The Reductive Cross-coupling Reaction And Preparation Of C9-C15 Fragment Of Benzenic Ansamycin

Ansamycin are a class of microbial metabolites belonging to polyketide natrual products,which possess sophisticated chemical structures and an array of biological activities,especially antineoplastic activity.Hence,these familial compouds have always interested chemists and biologists since their frist report in 1970.Autolytimycin,one representative of the phenol-type benzenic ansamycin found at the beginning of this century,is supposed to be an ideal leading compound with superior natures.However,natural resource of this kind of ansamycin is rare,and scanty efforts have been contributed to their Structure-Activity Relationship(SAR)researches.The reported synthese schemes are inappropriate to the SAR researches of ansamycin.Therefore,this article provides a convergent route to obtain autolytimycin and its structrual analogues via chemical total synthese.the scheme is beneficial for remedying the lack of sources of these compounds and serving for their SAR reseacher simultaneously.The main content of this article includes synthese of fragments of autolytimycin and its analogues and study on the alkyl-aryl reductive cross-coupling reaction applied to total synthese of autolytimycin.1.Preparation of C16-C21 fragment(aromtic fragment)of autolytimycin and its analogues.Taking 1,3-dinitrobenzene and 4-nitrophenol as raw materials,complete the preparation of aromtic fragment of autolytimycin and reblastatin,respectively.2.Preparation of C9-C15 fragment(half-ansa fragment)of autolytimycin and its analogues.Get the C9-C15 fragment of autolytimycin and its analogues from(R)-glyceraldehyde acetonide as starting material via 11 step chemical reactions,and optimize reactive conditions.Incidentally,finish the preparation of C9-C15-C14demethyl fragment analogue subjected to establish the C15-C16 bond of autolytimycin.3.Study on the alkyl-aryl reductive cross-coupling reactionOptimize preliminary reductive cross-coupling reactive conditions,settle reproducibility of the reaction and achieve the connection of C16-C21 fragment and C9-C15-C14demethyl fragment analogue with a moderate yield 60%.Subsequently,initiate the reseach on the reductive cross-coupling of aryl bromides with alkyl tosylate.