Research Of Asymmetric Synthesis Of 6-substituted-5,6-dihydrophenanthridine Compounds

The compounds which the main skeleton is 5,6-dihydrophenanthridine are important aza heterocycle compounds,bearing broad biological activities,which include anticancer,antiinflammatory,antimicrobial and so on.The methods of synthesis of the 5,6-dihydrophenanthridine derivatives have been widely reported,however,sythesis of the derivatives with high enantioselectivity have been rarely involved.We aimed at synthesis of chiral 6-substituted-5,6-dihydrophenanthridine compounds in this article,starting the research of methodology.[1,1'-biphenyl]-2-amine and carbonyl compounds with much stronger electrophilicity were utilized to synthesizing 6-substituted-5,6-dihydro phenanthridine compounds with higher yields and enantioselectivities under the effect of chiral imidodiphosphoric acid catalyst via Pictet-Spengler reaction.In this procedure of investigation,we first applied ten chiral imidodiphosphoric acids and phosphoric acids to catalyze asymmetric Pictet-Spengler reaction of3',5'-dimethoxy-[1,1'-biphenyl]-2-amine and 4-nitrobenzaldehyde.In room temperature,with toluene as solvent,we screened out the 3,3'-2-naphthalene-substituted H8-BINOL bisphosphorylimides as the most excellent catalyst.Later then,we investigated the solvent,the dosage of catalyst,the temperature of this reaction successively,and the optimal reaction condition was obtained,that is,under effect of 5 mol% 3,3'-2-naphthalene-substituted H8-BINOL bisphosphorylimides as catalyst,with chloroform as solvent,5? molecular sieve as additive in the reaction at 0?.Finally,we carried on the extension of two substrates with different substituent groups,and obtained 20 different chiral 6-aryl-5,6-dihydrophenanthridine derivatives via a Pictet-Spengler reaction under the basis of the optimal condition.The yield of product is up to 95%,and the enantioselectivity is up to 99%.Thereby,we can find that chiral phosphorylimides has strong activity and enantioselectivity for the synthesis of these compounds.In the basis of above-mentioned,we continued to investigate the activity of synthesizing the chiral 6-ester-5,6-dihydrophenanthridine compounds via the asymmetric Pictet-Spengler reaction,which applied 3',5'-dimethoxy-[1,1'-biphenyl]-2-amine and acetone acid ester as main substrates,chiral phosphorylimides as catalysts,and successively studied the effect of catalyst,solvent,the dosage of catalyst,the temperature of reaction with regard to the result of reaction as well.Thus,we obtained the optimal reaction condition,that is,under effect of 5 mol% 3,3'-2-naphthalene-substituted H8-BINOL bisphosphorylimides as catalyst,with CCl4 as solvent,5? molecular sieve as additive in the reaction at-40 ?.The yield of product is up to 90%,and the enantioselectivity is up to 83%.Above all,we utilized efficient chiral phosphorylimides catalysts to synthesize highly enantioselective 6-substituted-5,6-dihydrophenanthridine derivatives via the asymmetric Pictet-Spengler reaction,which also obtained much more remarkable achievements on research,and enriched the synthetic methods of this kind of aza heterocycle compounds.