Study On Phenanthrene Alkaloids Chemical Synthesis And Extracting Shikimic Acid From Anise

IntroductionPhenanthroindolizidine alkaloids with notable bioactivities are extracted from plants of Asclepiadaceae.The functions of alkaloids in plants include repelling grazing animals and microorganism,and competing with other plants.The bioactivities of these alkaloids include cytotoxic,mutagenicity,carcinogenicity and influence to biochemical process of target cells.It has been proved that Phenanthroindolizidine alkaloids have notable antitumor,and antileucocytosis activities.However,the low content in plants, difficulty to be extracted,low bioavailability,and side effects(e.g.serious central nervous system adverse reaction)confined their further utilization.Pharmacological researchs have shown us several possible action mechanisms,including effecting DNA molecule,inhibiting RNA duplication,and inhibiting the expression of protein.A tiny change in the chemical structure will lead to the change of the mechanism of action and the effect.Thus,we hope to develop new antitumor lead drugs through further research of the structure-activity relationship.It was found from the literature that aromatic skeleton is the necessary for the activity,the phenanthrene ring is suitable for the skeleton,there must be electron supporting group in the phenanthrene ring,e.g.methoxy group,and the position of the substitution group also influence the activity,at the same time,they must posses a free nitrogen atom.We designed the different substitution phenanthrene analogs with indole ring opened in order to research the structure and activity relationgship and find some new lead compound with high effect and low toxicity. MethodDifferent derivatives with indole ring opened were signed to increase the variety of the chemical structure and research new mechanism of action.α-phenyl-acrylic acid was obtained though Perkin condensation.Acyl amide was obtained through the acylation ofα-phenyl-acrylic acid and methyl ester valine.The phenanthrene ring formed through the oxidation-coupling reaction catalyzed by TTFA. At last,phenanthrene alkaloid analog was obtained by the reaction of amides reduction. In the process of synthesizing amide,the anhydrous operation was the key point.The amide reduction was the nodus of experiment.We used LiAlH₄/THF, NaBH₄-MeSO₃H/DMSO,and NaBH₄-I₂/THF system one by one.In this article we will discuss the amides reduction deeply.We chose several ways to carry out the reaction and compared of them.ResultWe summarized the chemical synthesis method formerly and made a deeply discussion of the synthesis technology of the phenanthrene alkoids.According to the structure activity relationship,we designed and synthesized the phenathrene alkoids analogs with indole ring opened.ConclusionSome phenathrene alkoids analogs with indole ring opened were obtained in this experiment by convenient and feasible methods.The methods of aromatic amides reduction were discussed. IntroductionShikimic acid is commonly used as raw material of synthesizing chiral drugs in medical industry,etc."Tamiflu" which is synthesized from shikimic acid.It is also important in the biosynthesis.Shikimic acid generally exists in Magnoliaceae evergreen shrub Illicium lanceolatum's fruit anise.The extracting shikimic acid from anise is still the main method,even if few technologies of preparing the shikimic acid were developed.There are few reports of the technology of extracting shikimic acid.Thus,this experiment is focused on the research of the technology of extracting shikimic acid from the anise.The purpose is to raise the product yield and lower the cost.MethodThe powder of the anis was extracted with 95%EtOH and then the solvent was evaporated.The residue was dissolved in the 80℃water,removed the dark green oil material on the surface of the water,followed by addition of formaldehyde formed precipitate.Then filtrated with diatomite and clear orange solution was obtained.Let it pass through an acetate anion exchange resin.Gather the eluent and remove the solvent. The residue dissolve in MeOH was heated with active carbon for hours.To filtrate the active carbon off and obtain clear solution.Remove the solvent,the rough shikimic was obtained.Pure shikimic was obtained by recrystallization from MeOH and toluene.ResultThe shikimic acid was gotten from anise by convenient and feasible method.The product yield is 4.2%.ConclusionIn this experiment we research the technology of extracting shikimic acid from anise.The method is convenient,feasible.The product yield reach 4.2%.It has the potential practical application and extensive commercial perspective.