Isolation Of Active Compounds From Acorus Tatarinowii And Studies On Design,Synthesis,Activity And Metabolism Of α-asaronol Esters

The Chinese medicine Acorus tatarinowii schott has a wide range of biological activities.In the experiment,Acorus tatarinowii schott was extracted and isolated.Then we studied the neuroprotective effects of some extracts,among whichα-asaronol had the best effect.In order to solve the problem of fast metabolism and low bioavailability ofα-asaronol in the body,according to the strategy of the strategy of Combination of Traditional Chinese Medicine Molecular Chemistry,12α-asaronol esters derivatives were designed,synthesized and assessed not only for anticonvulsant activity but also neurotoxic activity.In addition,the dissertation studied the metabolism of acetyl-α-asaronol ester with better activity in rats（compared withα-asarone）.The main content this paper is as follows:1.3 new phenylpropanoids and 22 known compounds were isolated from Acorus tatarinowii schott.Among them,γ-asaronol was a racemate,and the absolute configuration was determined by the modified Mosher method and ECD spectral data.The neuroprotective activities of compounds 5～9 in SH-SY5Y cells induced by H₂O₂ were evaluated.α-Asaronol had a protective effect on neuronal oxidative stress in the concentration range of 0.01-100μM.2.12α-Asaronol esters derivatives was synthesized and evaluated for anticonvulsant activity and neurotoxicity by maximum electroconvulsive（MES）experiment,pentylenetetrazole（PTZ）and 3-mercaptopropionic acid（3-MP）induced epilepsy mice models experiment and neurotoxic rotating rod experiment.The results showed that acetyl-α-asaronol ester and TMCA-α-asaronol can reduce the rate of clonic seizures caused by PTZ and 3-MP in mice,demonstrating obvious antiepileptic activity.3.Establishment of the HPLC method of a-asaronol and acetyl-α-asaronol ester in rats plasma to compare the pharmacokinetics of the two by intragastric administration and intravenous injection.The metabolic characteristics of acetyl-α-asaronol ester andα-asaronol in the rats after administration are non-compartmental models.At the same time after administration,the acetyl-α-asaronol ester group had higher content ofα-asaronol in rats than those in theα-asaronol group,indicating that acetyl-α-asaronol ester can significantly increase the content ofα-asaronol after entering the body and improve its bioavailability.