The Design,Preparation And Catalytic Activity Of Chiral Catalysts Base On Ent-beyerane Diterpene Compounds

Isosteviol is a tetracyclic diterpeniod with a beyerane skeleton,obtained by acid hydrolysis of Stevioside which is isolated from natural Stevia rebaudiana Bertoni.The natural product of isosteviol,with chiral centers and Superior chiral environment,is inexpensive,accessible and stable strcture.In addition,the presences of 16-Keto group and 19-carboxyl group provide further advantage which make the isosteviol easier to modify.Therefor,we designed and synthesized a novel class of conjugates by coupling small-molecule organocatalysis with isosteviol,in the basic skeleton,some small molecules can be connected to the catalytic activity of a group in order to design and synthesize novel chiral catalysts.In this dissertation,three novel chiral isosteviol-thiourea conjugates A1-A3 and two novel chiral isosteviol-imidazoline conjugates B1-B2 were synthesized by the inexpensive natural product,isosteviol with the modifying of 19-carboxyl group of A ring and 16-Keto group of D ring.And the asymmetric Michael addition reaction of isobutyraldehyde and N-phenylmaleimide were investigated using isosteviol-thiourea conjugates A1-A3 and isosteviol-imidazoline conjugates B1-B2.In addition,the asymmetric Aldol reaction of p-nitrobenzaldehyde and acetone/cyclohexanone were investigated using isosteviol-thiourea conjugates A1-A3 and isosteviol-imidazoline conjugates B1-B2.1.Three chiral isosteviol-thiourea conjugates A1-A3 of N-cyclohexyl-N’-(19-Bayeux alkyl esters-16β-)thiourea,N-indanol-N’-(19-Bayeux alkyl esters-16β-)thiourea,N-(2-aminoethyl)-N’-(19-Bayeux alkyl esters-16β-)thiourea were synthesized by a process starting from Stevioside,followed by acid hydrolysis,esterification reaction,reduction reaction,methyl sulfonylation reaction,azido reaction,isocyanate reaction,and reaction with compounds containing amino-group.2.Two chiral isosteviol-imidazoline conjugates B1-B2 of 16-imidazole-19-Bayeux alkyl esters,16-benzimidazole-19-Bayeux alkyl esters were synthesized by ent-16-Methyl sulfonic acid ester-19-Bayeux alkyl reaction with imidazole/benzimidazole under the alkaline condition.3.The asymmetric Michael addition reaction of isobutyraldehyde and N-phenylmaleimide was investigated using isosteviol-thiourea conjugates A1-A3 and isosteviol-imidazoline conjugates B1-B2.Experimental results showed that catalysts of A1-A2 had no catalytic activity.Under the condition of using 10mol%A3 as catalyst,chloroform being solvent,25℃ of reaction temperature,6 hours,the yield was 13%with no enantioselectivity.Under the condition of using 10mol%B1 as catalyst,chloroform being solvent,25℃ of reaction temperature,6 hours,the yield was 13%with no enantioselectivity.Under the condition of using 10mol%B2 as catalyst,chloroform being solvent,25℃ of reaction temperature,6 hours,the yield was 9%with no enantioselectivity.4.The asymmetric Aldol reaction of p-nitrobenzaldehyde and acetone was investigated using isosteviol-thiourea conjugates A1-A3 and isosteviol-imidazoline conjugates B1-B2.Experimental results showed that catalysts of A1-A2,B1-B2 had no catalytic activity.Under the condition of using 10mol%A3 as catalyst,acetone being solvent,25℃of reaction temperature,24 hours,the yield was 36%with no enantioselectivity.5.The asymmetric Aldol reaction of p-nitrobenzaldehyde and cyclohexanone was investigated using isosteviol-thiourea conjugates A1-A3 and isosteviol-imidazoline conjugates B1-B2.Experimental results showed that catalysts of A1-A2,B1-B2 had no catalytic activity.Under the condition of using 10mol%A3 as catalyst,cyclohexanone being solvent,25℃ of reaction temperature,24 hours,the yield was 28%with no enantioselectivity.