The Studies On The Syntheses Of 1, 4-Benzodioxane Neolignan Derivatives And Dihydrobenzofuran Neolignan Derivatives With Biological Activities

1,4-Benzodioxane neolignans and dihydrobenzofuran neolignans are widespread in nature, exhibit a broad range of biological activities and are potent ingredients of many officinal plants. In order to meet the needs for selecting the substances with biological activities and opening up new drugs this thesis aims at the studies on the syntheses of 1,4-benzodioxane neolignan derivatives and dihydrobenzofuran neolignan derivatives.First, the classification, biological activities, new extract method, structure identification method and rapidly being checked method of lignan compounds were introduced in the thesis. Meanwhile, their application in pharmacology and taxonomy was also mentioned. And the biological activities and the previous synthetic reports of 1,4-benzodioxane neolignans and benzofuran neolignans were also introduced briefly.Aiming at constructing 1,4-benzodioxane skeleton, synthetic routes were devised. On the basis of these devices, four compounds (1)⁴ have been firstly synthesized, which belong to 1,4-benzodioxane neolignan derivatives, and the synthetic routes as following:1. Starting from 3-methoxy-4-hydroxybenzaldehyde, p-hydroxybenzaldehyde and m-benzenediol, 3-methoxy-4,5-dihydroxybenzaldehyde was made from 3-methoxy-4-hydroxybenzaldehyde via bromination and hydrolysis in two steps; 3-(4-hydroxy phenyl)-2-propenol was made from p-hydroxy benzaldehyde via Knoevenagel reaction, esterification and reduction in three steps; 2-hydroxy-4-methoxyacetophenone was made from m-benzenediol via acetylation and selective methylation in two steps.2. Starting from 3-methoxy-4,5-dihydroxy benzaldehyde and 3-(4-hydroxyphenyl)-2-propenol compound (1) was synthesized via Ag2O-catalyzed biomimetic oxidative coupling as the key step.3. Starting from 3-methoxy-4,5-dihydroxy benzaldehyde and l-chloro-2,3-epoxy propane compound (2) was synthesized via intramolecular SN2 reaction as the key step.4. 3-Methoxy-4,5-dihydroxybenzaldehyde reacted with 1,2-dibromoethane through intramolecular SN2 reaction as the key step to give the compound, which reacted with 2-hydroxy-4-methoxyacetophenone via aldol condensation to give compound (3). Compound (3) with sodium acetate in unhydrous ethanol was cycled to give compound (4).Aiming at constructing dihydrobenzofuran skeleton, synthetic routes were devised.On the basis of these devices, three compounds (5)⁷ have been synthesized, which belong to dehydrobenzofuran neolignans. Decorating the structure of compound (6), 8,5'-neolignan compound (8) has been firstly synthesized, which supplies a new synthetic approach to 8,5'-neolignan with biological activities. The synthetic routes as following:1. Starting from 3-methoxy-4-hydroxybenzaldehyde and malonic acid, compound (5) was synthesized via Knoevenagel reaction, esterification and Ag2O-catalyzed biomimetic oxidative coupling in three steps.2. Starting from p-hydroxybenzaldehyde and malonic acid, compound (6) was synthesized via Knoevenagel reaction, esterification and Ag2O-catalyzed biomimetic oxidative coupling in three steps.3. In the presence of aluminium chloride with 3 equivalent of lithium aluminium hydride compound (6) was reduced in room temperature to give compound (7).4. The 4-OH group of compound (6) could not been methylated with dimethyl sulfate or methyl iodide in the presence of potassium carbonate, in which reaction compound (8) was synthesized. The being synthesized mechanism of 8,5'-neolignan (8) was undetermined.All of these synthesized new compounds (1)⁸ have been confirmed by MS, IR and 1H NMR.