Regio-And Stereoselective Synthesis Of Resveratrol Oligomers

The regio- and stereo-selective synthesis of resveratrol oligomers starting from resveratrol and its derivatives were reviewed in this paper. The regioselective oxidative coupling reactions of 3,5-di-tert-butyl-11,13-di-acetoxy-resveratrol catalyzed by Fe3+ oxidants were studied in detail. The total synthesis of three resveratrol oligomers were finally accomplished by a series of the structural conversion and global deprotection reactions of the several coupling products. Additionally, the preparation of chiral derivatives of 3,5-di-tert-butyl-resveratrol and their oxidative coupling reactions were also preliminarily investigated. The thesis was divided into three parts:1. IntroductionThe development of biomimetic and chemically selective synthesis of stilbene oligomers in recent years was reviewed. And the study on the asymmetric synthesis of resveratrol oligomers was briefly introduced.2. Total synthesis of natural product-pallidol and other resveratrol dimmers 14 a, 14 b, and 16.The coupling precursor 8 or 10, was synthesized through eight steps by using methyl 3,5-dihydroxybenzoate as the starting material. By using the regioselective oxidative coupling reaction as the key step, the coupling precursors were catalyzed by different metal oxidants(FeC l3 and FeCl3 ?6H2O) in several solvent systems to afford the dimeric structures 9a, 9b, 11 a, 11 b, 11 c, and 12 a, 12 b, 12 c as well as 13 a, 13 b, respectively. Trifluoroacetic acid was used to remove all the tert-butyl and acetyl protecting groups from the coupling dimers 9, 11 or 13 in one-pot reaction, and smoothly produced the same natural product- pallidol in high yield. In addition, 13 was subjected to debutylation and deacetylation in two steps to give an unnaturral oligomer 16. The mixture of 12 a, 12 b and 12 c also underwent the global depretection catalyzed by trifluoroacetic acid to synthesize two resveratrol oligomers 14 a and 14 b.3. Preliminary study on the asymmetric synthesis of resveratrol oligomersChiral group R* was introduced into 3,5-di-tert-butyl- resveratrol by a simple esterification reaction, and the coupling reaction of this chiral coupling precursor was also preliminarily investigated. Furthermore, another chiral resveratrol derivative was prepared by using the Perkin condensation reaction as a key step to construct double bond of stilbene, into which a chiral ester groups was introduced tthrough subsequent esesterification. At present, the synthesis and oxidative coupling reactions of the chiral derivatives of 3,5-di-tert-butyl-resveratrol were ongoing in our laboratory.This paper mainly studies the oxidative coupling reactions of 3,5-di-tert-butyl-11,13-di-acetoxy-resveratrolunder the different catalyst and solvent conditions. The introduction of tert-butyl and acetyl protecting groups into resveratrol largely improved the regioselectivity of the coupling reaction. The structural modification and subsequent global deprotection of coupling products finally accomplished the total synthesis of natural product-pallidol and three unnatural resveratrol oligomers-14 a, 14 b and 16. The preparation and oxidative coupling reactions of chiral resveratrol derivatives were also explored in this paper. O ur research results offered an important references on the regio- and stereo-selective synthesis of resveratrol oligomers in the future.