Study On The Asymmetric Total Synthesis Of Pedamide-the Right Half Of Pederin And Flavan

Asymmetric total synthesis of pedamide,the right half of(-)-pederin was studied. And we made much attempts to asymmetrically synthesize two natural flavan like compounds,broussin and demethylbroussin in our paper.The paper mainly involved three parts.1.The developments of the study of the total synthesis of pederin like natural compounds(review)The separation and biologic activity of pederin like natural compounds were introduced.The basic blocks in the syntheses of pederin like compounds including pederin,mycalamide and psymberin were summarized.According to the reaction forming the skeleton in every block,the syntheses of the blocks were summarized. And the development of the study of the total syntheses of pederin like compounds was reviewed,pedamide,the main block in the synthesis of pederin,was applied as the key intermediate in all of the synthesis of pederin according to the literature. Development of asymmetric syntheses of pedamide was described in detail. Biosyntheses of pederin were developed along with biologic technology.And the biosynthetic methods of pederin like compounds were summarized.2.Stereoselectively formal syntheses of pedamide,the right half of(+)-pederinThe character of configuration and synthetic strategy of pederin was introduced briefly.Syntheses of racemic pedamide and(-)-benzylpedamide were studied. Firstly,starting from 2,2-dimethyl-1,3-propan-diol,synthesis of(±)-pedamide was finished in 17 steps.The pyran ring was formed in a S_N2 substitution of hydroxyl and epoxide.In the scheme,the key reactions were Grignard reaction, dihydroxylation,S_N2 substitution of hydroxyl and epoxide under acidic conditions and etc.Secondly,starting from 2,2-dimethyl-1,3-propan-diol,asymmetric syntheses of(-)-benzylpedamide were finished in a scheme with 14 steps and another scheme with 16 steps.The pyran rings were formed in an I₂-induced heterocyclization of hydroxyl and olefin.In the two schemes,the key reactions were Brown's asymmetric allylation,substrate-controlled and Lewis acid-catalyzed asymmetric allylation,I₂-induced asymmetric heterocyclization and Sharpless asymmetric dihydroxylation.In addition,an asymmetric synthesis was investigated based on the S_N2 substitution of hydroxyl and epoxide intermolecular.3.Stereoselectively total syntheses of natural flavanThe biologic and pharmacologic activities of two flavans were introduced including broussin and demethylbroussin.Asymmetric syntheses of broussin and demethylbroussin were studied.Starting from 2,4-dihydroxy-benzaldehyde and 4-hydroxy-acetophenone,asymmetric syntheses of broussin and demethylbroussin were finished in two schemes,which were both in 14 steps.The key reaction included Aldol condensation,CBS asymmetric reduction and Mitsnobu reaction.In the experiment,ee value of the chiral alcohol formed in CBS asymmetric reduction was over 85%.The treatment of the chiral alcohol with Mitsnobu reaction followed by deprotection gave racemic product.But these experiences could be used for reference in the syntheses of flavan like compounds.In summary,(±) -pedamide and(-)-benzylpedamide were synthesized through short schemes.In addition,two natural flavans were synthesized including broussin and demethylbroussin.In our work,72 compounds were synthesized as the intermediate or target compounds.Among of them,35 compounds were new.The configurations of all the compounds were proved by NMR,MS spectrum and etc.