Oxidative Coupling Reaction Of Halogenated Resveratrol Monomers

The biomimetic oxidative coupling reaction is the concise approach to the synthesis of resveratrol oligomers.However,due to the diverse coupling patterns of resveratrol radical mesmors,the uncontrolled oxidative reaction always lead to the complex products with low yields,which make a big challenge to the separation and purification of coupling products.Therefore,our team proposed the introduction of positional protecting groups(bromine,iodine,chiral menthyl)to the C-3 and C-5 of resveratrol monomer in order to enhance the regioselectivity and stereoselectivity in the oxidative coupling reactions.We intend to analyze the dimeric intermediates structures obtained in Fe Cl3 ?6H2O-catalyzed oxidation of protected resveratrol in the different solvents,and investigate the deprotection reaction conditions as well as the final natural or unnatural products we obtained.The thesis mainly discusses the following aspects:In the first chapter,the achievement and methods on the regioselective biomimetic synthesis and chemical synthesis of natural resveratrol dimers in recent years were briefly introduced.And the application of bromine and iodine atom as the positional protecting groups in the biomimetic synthesis of natural lignans was also summarized.In the second chapter,the FeCl3?6H2O-catalyzed oxidative coupling reaction of brominated resveratrol precursor was studied.The effects of six different solvent systems including acetone,benzene-acetone,acetone-water,acetone-buffer(pH = 5.4)solution,methanol and methanol-dichloromethane on the coupling products and yields were discussed in detail.The 8-8-coupled intermediates 9a/9b,10,12,14,15a/15 b,and 16a/16 b as well as8-10-coupled dimers 11 and 13 were separated and characterized,respectively.Finally,dimeric intermediate 11 was subjected to the different deprotection reaction conditions to generate natural products(±)-?-viniferin,(±)-ampelopsin B and(±)-gnetins F as well as an unnatural dimer 17.In the third chapter,the FeCl3?6H2O-catalyzed oxidative coupling reaction of3,5-diiodo-resveratrol monomer was investigated.The effects of four different solvent systems including acetone,benzene-acetone,acetone-water and acetone-buffer(pH = 5.4)solution on the coupling products were discussed.8-8-coupled dimers 22 and 24,and 8-10-coupled dimer 23 were obtained from the above coupling reactions.In the fourth chapter,the region-and stereo-selective oxidative coupling reaction was preliminarily explored by using the chiral auxiliaries as positional protec tive groups of resveratrol.Various different reactions were attempted expecting to introduce chiral menthyl groups in C-3 and C-5 of resveratrol or chiral 2,2-dimethyl-cyclopropanecarboxyl groups in C-12 and C-14 of resveratrol.The current exploration did not get successful results.We synthesized successfully the natural benzofuran-type resveratrol dimer(±)-?-viniferin in high yield through the investigation of oxidation coupling reactions of halog enated resveratrol monomers.The structure of(±)-?-viniferin could be converted into t he diverse resveratrol oligomers through the isomerization or oligomerization.The first application of bromine and iodine as the positional protecting groups in the biomimet ic synthesis of natural oligostilbenes successfully achieved the regioselective control in the radical coupling reaction.The chiral auxiliaries as positional protecting groups we re introduced into resveratrol monomer to explore their stereoselective effects in the oxidative coupling reactions.This is a beneficial attempt on the asymmetric biomimet ic synthesis of resveratrol dimers and have significance to the study of the chiral synt hesis of oligostilbenes.