Study On The Oxidative Coupling Reactions Of Phenylpropanoids

This paper described the oxidative coupling reactions of phenylpropanoid compounds and the regioselective effects of tert-butyl or bromine as the position-protecting group of feruloytyamide on the oxidative coupling reactions for the total synthesis of natural liganamide(±)-canabisin D. Additionally, the oxidative coupling reactions of phenylpropanoid alcohols and phenylpropanoid esters under the metal or enzyme catalytic conditions were also preliminarily investigated. This thesis was divided into the following three parts.Part one,review.The discovery, naming and classification of lignans were introduced in brief. And the discovery of several liganamides in recent years as well as the research progress on the chemical and biomimetic synthesis of lignans were reviewed.In the second part, full details of the Biomimetic synthesis of natural product(±)-Canabisin D. The coupling precursor 2-13 was prepared through five-step reaction starting from 4-methyl guaiacol on which a tert-butyl group as the position-protecting group was introduced. The oxidative coupling reaction of 2-13 catalyzed by FeCl3·6H2O formed the coupling dimer 2-14 and a small quantity of 2-16, which possessed the expected aryldihydronaphthalene skeleton. The final debutylation of 2-14 completed the synthesis of(±)-canabisin D. Compound 2-23 was prepared through three-step reaction starting from vanillin and Br atom as the position-protecting group. The oxidative coupling reaction of 2-23 catalyzed by FeCl3·6H2O formed 2-24, which possessed the basic aryldihydronaphthalene skeleton. The final debromination of 2-24 also complished the synthesis of(±)-canabisin D.Thus,(±)-Canabisin D were totally synthesized by the above two methods. The problems encountered in the synthetic routes were discussed and the coupling mechanisms were explained. In contrast, Br atom as the position-protecting group had obvious advantages in the regioselective coupling reaction over bukyl tert-butyl group because of the easily purification and higher yield in the key coupling step.In the third part, study on the oxidative coupling reactions of phenylpropanoids compounds. I hoped to construct the aryldihydronaphthalene skeletons by using the regioselective biomimetic oxidative coupling reactions of phenylpropanoid compounds. Currently the oxidative coupling reactions of phenylpropanoid alcohol and phenylpropanoid ester catalyzed by silver carbonate and horseradish peroxidase were studied and dimers 3-25 and 3-26 were obtained. The structure of coupling products have not been determined to date due to their spectra complexity. At present, the oxidative coupling reactions of other phenylpropanoid esters under metallic oxidants conditions were ongong in our group and the desired results have not yet achieved owing to the complexity of coupling reactions and uncertainty of the removal of the protecting group.In this paper, the biomimetic synthesis of natural lignan(±)-Canabisin D was successfully accomplished through two different regioselective routes. The asymmetric biomimetic synthesis of aryldihydronaphthalene lignans was in progress. The regioselectively and stereoselectively controlled strategy for the synthesis of optically active natural lignans was attempted by introducing the position-protecting group and chiral auxiliary group simultaneously in the coupling precursor. This part of the work was being carried out in the laboratory. Structural determinations of the isolated compounds were based on 1H NMR, 13 C NMR, NOESY, 1H-1H COSY, HMBC spectra, and HRMS analysis. Spectra and analytical data have carried out a detailed explanation in the paper.